PMID-sentid Pub_year Sent_text comp_official_name comp_offset protein_name organism prot_offset 33727089-0 2021 4-Acetylantroquinonol B downregulates CDK2/CDK4 expression and DNA damage response signaling for triggers programmed cell death in triple negative breast cancer cells. 4-acetylantroquinonol 0-21 cyclin dependent kinase 2 Homo sapiens 38-42 33727089-13 2021 We also evidenced the potential of a natural small compound, 4-AAQB, in therapy targeting the CDK2/4 and DDR in TNBC cells. 4-acetylantroquinonol B 61-67 cyclin dependent kinase 2 Homo sapiens 94-100 33727089-3 2021 Here we investigated the dual therapeutic targeting of CDK2/CDK4 using 4-Acetylantroquinonol B (4-AAQB) against TNBC cells. 4-acetylantroquinonol B 71-94 cyclin dependent kinase 2 Homo sapiens 55-59 33727089-3 2021 Here we investigated the dual therapeutic targeting of CDK2/CDK4 using 4-Acetylantroquinonol B (4-AAQB) against TNBC cells. 4-acetylantroquinonol B 96-102 cyclin dependent kinase 2 Homo sapiens 55-59 33727089-4 2021 METHODS: We extended the study to the effects of CDK2, CDK4, and CDK6 inhibition via 4-AAQB treatment using TNBC cell lines. 4-acetylantroquinonol B 85-91 cyclin dependent kinase 2 Homo sapiens 49-53 33727089-8 2021 Our docking indicated a high affinity of 4-AAQB for binding with CDK2 and CDK4. 4-acetylantroquinonol B 41-47 cyclin dependent kinase 2 Homo sapiens 65-69 33727089-9 2021 Treatment of TNBC cells with 4-AAQB suppressed expression of CDK2 and CDK4 in vitro. 4-acetylantroquinonol B 29-35 cyclin dependent kinase 2 Homo sapiens 61-65 33912870-7 2021 Moreover, the molecular docking in silico study of the four major chemical constituents of the oil at the CDK2 binding site demonstrated marked interactions with the ATP-binding site residues through alkyl & Pi-alkyl interactions. Adenosine Triphosphate 166-169 cyclin dependent kinase 2 Homo sapiens 106-110 33784602-0 2021 Mechanistic selectivity investigation and 2D-QSAR study of some new antiproliferative pyrazoles and pyrazolopyridines as potential CDK2 inhibitors. Pyrazoles 86-95 cyclin dependent kinase 2 Homo sapiens 131-135 33784602-0 2021 Mechanistic selectivity investigation and 2D-QSAR study of some new antiproliferative pyrazoles and pyrazolopyridines as potential CDK2 inhibitors. pyrazolopyridine 100-117 cyclin dependent kinase 2 Homo sapiens 131-135 33784602-7 2021 Docking in CDK2 ATP binding site, co-crystallized with R-Roscovitine, demonstrated analogous interactions and comparable binding energy with the native ligand. Adenosine Triphosphate 16-19 cyclin dependent kinase 2 Homo sapiens 11-15 33784602-7 2021 Docking in CDK2 ATP binding site, co-crystallized with R-Roscovitine, demonstrated analogous interactions and comparable binding energy with the native ligand. Roscovitine 55-68 cyclin dependent kinase 2 Homo sapiens 11-15 33784602-8 2021 2D QSAR sighted the possible structural features governing the CDK2 inhibition activity elicited by the studied pyrazolo[3,4-b]pyridines. pyrazolo(3,4-b)pyridine 112-136 cyclin dependent kinase 2 Homo sapiens 63-67 32787531-5 2021 From the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed the best inhibitory activities towards the Human topoisomerase IIalpha, and Quercetin was predicted to be the best agent against VEGFR-2. daidzein 96-104 cyclin dependent kinase 2 Homo sapiens 89-94 32787531-5 2021 From the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed the best inhibitory activities towards the Human topoisomerase IIalpha, and Quercetin was predicted to be the best agent against VEGFR-2. Quercetin 188-197 cyclin dependent kinase 2 Homo sapiens 89-94 32008465-7 2021 In cancer cells, Vit C, in a pharmacological dose, decreased cell proliferation through an inhibitory effect on cyclin-dependent kinase 2 (CDK2) (4.4-fold; p < 0.01), mainly due to the stimulatory effect on the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21 and p53 (3.2- and 2.8-fold, respectively; p < 0.001), but not caspase pathway. Ascorbic Acid 17-22 cyclin dependent kinase 2 Homo sapiens 112-137 32008465-7 2021 In cancer cells, Vit C, in a pharmacological dose, decreased cell proliferation through an inhibitory effect on cyclin-dependent kinase 2 (CDK2) (4.4-fold; p < 0.01), mainly due to the stimulatory effect on the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21 and p53 (3.2- and 2.8-fold, respectively; p < 0.001), but not caspase pathway. Ascorbic Acid 17-22 cyclin dependent kinase 2 Homo sapiens 139-143 32787531-5 2021 From the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed the best inhibitory activities towards the Human topoisomerase IIalpha, and Quercetin was predicted to be the best agent against VEGFR-2. epigallocatechin gallate 21-45 cyclin dependent kinase 2 Homo sapiens 89-94 33986726-12 2021 Potential therapeutic agents are EGFR inhibitors such as gefitinib and lapatinib, the purine analog R-roscovitine by dissociation of CDK2/Cyclin E complex, the HSP90 inhibitor silibinin (novobiocin), to reduce resistance to glucocorticoid-mediated negative feedback, and BRAF inhibitors vemurafenib and dabrafenib in BRAF V600E positive tumors. purine 86-92 cyclin dependent kinase 2 Homo sapiens 133-137 34048990-0 2021 Propofol suppressed cell proliferation and enhanced apoptosis of bladder cancer cells by regulating the miR-340/CDK2 signal axis. Propofol 0-8 cyclin dependent kinase 2 Homo sapiens 112-116 34048990-3 2021 Here, we proved that propofol regulated miR-340/CDK2 axis to suppress bladder cancer progression in vitro. Propofol 21-29 cyclin dependent kinase 2 Homo sapiens 48-52 34048990-14 2021 Finally, inhibition of CDK2 could partly reversed the effect of miR-340 inhibitor on cell proliferation and cell apoptosis of propofol-treated 5637 cells. Propofol 126-134 cyclin dependent kinase 2 Homo sapiens 23-27 34048990-15 2021 CONCLUSION: In total, our results proved that targeting miR340/CDK2 axis was novel to enhance the anti-tumor effects of propofol in bladder cancer in vitro, and our study provided alternative therapeutic strategies for clinical treatment of bladder cancer. Propofol 120-128 cyclin dependent kinase 2 Homo sapiens 63-67 33684714-12 2021 In addition, the MM-PBSA calculations ascribed the lowest binding free energy to the 7d-CDK2 complex (-323.69 +- 15.17 kJ/mol). poly(tetramethylene succinate-co-tetramethylene adipate) 20-24 cyclin dependent kinase 2 Homo sapiens 88-92 32757998-8 2021 Association of the extract with cisplatin enhanced the latter"s antiproliferative effect, arrested the cell cycle at the S phase by CDK2 modulation, and reduced the number of anti-cyclin D1-stained HepG2 cells. Cisplatin 32-41 cyclin dependent kinase 2 Homo sapiens 132-136 33931002-3 2021 The present study aims at identifying the selective inhibitors for ATP binding site in CDK proteins (CDK1, CDK2, CDK4, and CDK5) following a multi-target drug designing approach. Adenosine Triphosphate 67-70 cyclin dependent kinase 2 Homo sapiens 107-111 34002651-8 2021 Our results showed that MG132 downregulated the expression of antiapoptotic proteins, including CDK2, CDK4, Bcl-xL, and Bcl-2, whereas it upregulated the expression of proapoptotic proteins, including p21, p27, p53, p-p53 (ser15, ser20, and ser46), cleaved forms of caspase-3, caspase-7, caspase-9, and PARP, and FOXO3 in U2OS cells. benzyloxycarbonylleucyl-leucyl-leucine aldehyde 24-29 cyclin dependent kinase 2 Homo sapiens 96-100 33684714-0 2021 Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations. isatin-thiazolo[3,2-a]benzimidazole 15-50 cyclin dependent kinase 2 Homo sapiens 68-72 33684714-3 2021 In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. Isatin 106-112 cyclin dependent kinase 2 Homo sapiens 259-263 33684714-3 2021 In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. [1,3]thiazolo[3,2-a]benzimidazole 140-168 cyclin dependent kinase 2 Homo sapiens 259-263 33684714-3 2021 In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. tbi 170-173 cyclin dependent kinase 2 Homo sapiens 259-263 33684714-3 2021 In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. hydrazide 201-210 cyclin dependent kinase 2 Homo sapiens 259-263 33684714-4 2021 The large tricyclic TBI motif is anticipated to achieve a plethora of hydrophobic interactions within the CDK2 binding site. tbi 20-23 cyclin dependent kinase 2 Homo sapiens 106-110 33684714-9 2021 The docking simulations unveiled, as expected, the ability of the TBI ring to well-accommodate and establish several hydrophobic interactions within a hydrophobic pocket in the CDK2 binding site. tbi 66-69 cyclin dependent kinase 2 Homo sapiens 177-181 33995088-6 2021 TB treatment caused the downregulating of c-myc, cyclin D, CDK2, and CDK4 and upregulating of p21 and p27 in the HOG cell, while TB increased P53, p21, and p27 levels and decreased the levels of cell cycle regulator proteins such as CDK and cyclin A/B in the U251 cells. theabrownin 0-2 cyclin dependent kinase 2 Homo sapiens 59-63 33995088-6 2021 TB treatment caused the downregulating of c-myc, cyclin D, CDK2, and CDK4 and upregulating of p21 and p27 in the HOG cell, while TB increased P53, p21, and p27 levels and decreased the levels of cell cycle regulator proteins such as CDK and cyclin A/B in the U251 cells. theabrownin 0-2 cyclin dependent kinase 2 Homo sapiens 59-62 33986726-12 2021 Potential therapeutic agents are EGFR inhibitors such as gefitinib and lapatinib, the purine analog R-roscovitine by dissociation of CDK2/Cyclin E complex, the HSP90 inhibitor silibinin (novobiocin), to reduce resistance to glucocorticoid-mediated negative feedback, and BRAF inhibitors vemurafenib and dabrafenib in BRAF V600E positive tumors. Roscovitine 100-113 cyclin dependent kinase 2 Homo sapiens 133-137 33995632-9 2021 Treatment with lenvatinib decreased the expression of MMP-2, CEMIP, CDK2, CDK4 and cyclin D1, and increased the expression of cleaved caspase-9, which was mediated by the inactivation of the PI3K/AKT pathway in vitro. lenvatinib 15-25 cyclin dependent kinase 2 Homo sapiens 68-72 33953676-6 2021 The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). astragalin 24-34 cyclin dependent kinase 2 Homo sapiens 305-309 33965780-0 2021 A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene. Urea 94-98 cyclin dependent kinase 2 Homo sapiens 24-28 33965780-0 2021 A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene. 1, 4-diisocyanatobenzene 114-138 cyclin dependent kinase 2 Homo sapiens 24-28 33965780-10 2021 Our study conclude good binding propensity for active-tunnel of ERK/MAP kinase and CDK2 proteins, by 3d (1,1"-(1,4-phenylene) bis(3-(2-chlorobenzyl)urea)), to suggest that the designed and synthesized 3d is to use as selective novel nuclei in anti-cancer chemotherapeutics. Urea 148-152 cyclin dependent kinase 2 Homo sapiens 83-87 33876395-12 2021 UHRF2 bound to CDK2 directly and enhanced UHRF2 phosphorylation at serine 643. Serine 67-73 cyclin dependent kinase 2 Homo sapiens 15-19 33858315-0 2022 Evaluation of Benzamide-chalcone Derivatives as EGFR/CDK2 inhibitor: Synthesis, in-vitro Inhibition, and Molecular Modeling Studies. benzamide 14-23 cyclin dependent kinase 2 Homo sapiens 53-57 33711765-0 2021 Imidazo[1,2-c]pyrimidin-5(6H)-one inhibitors of CDK2: Synthesis, kinase inhibition and co-crystal structure. 3,N(4)-ethenocytosine 0-33 cyclin dependent kinase 2 Homo sapiens 48-52 33711765-2 2021 We recently identified substituted imidazo[1,2-c]pyrimidin-5(6H)-ones as inhibitors of cyclin-dependent kinase 2 (CDK2). imidazo[1,2-c]pyrimidin-5(6h)-ones 35-69 cyclin dependent kinase 2 Homo sapiens 87-112 33711765-2 2021 We recently identified substituted imidazo[1,2-c]pyrimidin-5(6H)-ones as inhibitors of cyclin-dependent kinase 2 (CDK2). imidazo[1,2-c]pyrimidin-5(6h)-ones 35-69 cyclin dependent kinase 2 Homo sapiens 114-118 33711765-6 2021 The co-crystal structure of 3b in complex with fully active CDK2 was solved, revealing the binding mode of 3b in the ATP pocket and a hydrogen bonding interaction with hinge region residue Leu83. Adenosine Triphosphate 117-120 cyclin dependent kinase 2 Homo sapiens 60-64 33711765-6 2021 The co-crystal structure of 3b in complex with fully active CDK2 was solved, revealing the binding mode of 3b in the ATP pocket and a hydrogen bonding interaction with hinge region residue Leu83. Hydrogen 134-142 cyclin dependent kinase 2 Homo sapiens 60-64 33858315-0 2022 Evaluation of Benzamide-chalcone Derivatives as EGFR/CDK2 inhibitor: Synthesis, in-vitro Inhibition, and Molecular Modeling Studies. Chalcone 24-32 cyclin dependent kinase 2 Homo sapiens 53-57 33858315-14 2022 Binding mode analysis for CDK2 inhibition studies indicate that hydrogen bonding interaction with Lys 33 and Leu83 are important for the activity. Hydrogen 64-72 cyclin dependent kinase 2 Homo sapiens 26-30 33858315-14 2022 Binding mode analysis for CDK2 inhibition studies indicate that hydrogen bonding interaction with Lys 33 and Leu83 are important for the activity. Lysine 98-101 cyclin dependent kinase 2 Homo sapiens 26-30 33858315-17 2022 CONCLUSION: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases. benzamide 18-27 cyclin dependent kinase 2 Homo sapiens 157-161 33858315-17 2022 CONCLUSION: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases. Chalcone 40-48 cyclin dependent kinase 2 Homo sapiens 157-161 33883905-8 2021 Calycosin downregulated the cell cycle proteins cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, and cyclin E; upregulated p21 and p27; and arrested cells in the G0/G1 phase. 7,3'-dihydroxy-4'-methoxyisoflavone 0-9 cyclin dependent kinase 2 Homo sapiens 48-73 33912552-3 2021 Polydatin efficiently inhibited cervical cancer cell proliferation by regulating cell cycle-related proteins including p21, p27, CDK2, CDK4, Cyclin D1, and Cyclin E1. polydatin 0-9 cyclin dependent kinase 2 Homo sapiens 129-133 33883905-8 2021 Calycosin downregulated the cell cycle proteins cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, and cyclin E; upregulated p21 and p27; and arrested cells in the G0/G1 phase. 7,3'-dihydroxy-4'-methoxyisoflavone 0-9 cyclin dependent kinase 2 Homo sapiens 75-79 33550184-0 2021 Tetrahydroindazole inhibitors of CDK2/cyclin complexes. Tetrahydroindazole 0-18 cyclin dependent kinase 2 Homo sapiens 33-37 33640611-4 2021 Here, we studied the mechanism of enhancement of CDK2 activity by E1A, using the E1A variant forms which selectively contain CR domains. Chromium 125-127 cyclin dependent kinase 2 Homo sapiens 49-53 33640611-7 2021 Concomitantly, the specific activity of the 13S-associated CDK2 was highest among them. 5-chloro-3-tert-butyl-2'-chloro-4'-nitrosalicylanilide 44-47 cyclin dependent kinase 2 Homo sapiens 59-63 33749525-0 2021 Identification of selective cyclin-dependent kinase 2 inhibitor from the library of pyrrolone-fused benzosuberene compounds: an in silico exploration. 2H-Pyrrol-2-one 84-93 cyclin dependent kinase 2 Homo sapiens 28-53 33749525-0 2021 Identification of selective cyclin-dependent kinase 2 inhibitor from the library of pyrrolone-fused benzosuberene compounds: an in silico exploration. benzosuberene 100-113 cyclin dependent kinase 2 Homo sapiens 28-53 33611192-0 2021 Design, synthesis, and biological evaluation of 4-benzoylamino-1H-pyrazole-3-carboxamide derivatives as potent CDK2 inhibitors. 4-benzoylamino-1h-pyrazole-3-carboxamide 48-88 cyclin dependent kinase 2 Homo sapiens 111-115 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. dc-k2in212 49-59 cyclin dependent kinase 2 Homo sapiens 94-98 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. dc-k2in212 49-59 cyclin dependent kinase 2 Homo sapiens 127-131 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. dc-k2in212 49-59 cyclin dependent kinase 2 Homo sapiens 127-131 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. Carbon 50-51 cyclin dependent kinase 2 Homo sapiens 94-98 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. Carbon 50-51 cyclin dependent kinase 2 Homo sapiens 127-131 33611192-6 2021 The molecular modeling illustrated that compound DC-K2in212 had the similar binding mode with CDK2 as C-73, the most selective CDK2 inhibitor reported so far, which might account for selectivity against CDK2 over CDK1. Carbon 50-51 cyclin dependent kinase 2 Homo sapiens 127-131 33611192-8 2021 Therefore, compound DC-K2in212 could serve as a potential CDK2 inhibitor for further development. dc-k2in212 20-30 cyclin dependent kinase 2 Homo sapiens 58-62 33782497-9 2021 In contrast, gammaH2AX induced by single agent ATRi and CHK1i requires a high threshold activity CDK2. gammah2ax 13-22 cyclin dependent kinase 2 Homo sapiens 97-101 33759321-7 2021 SRA exhibited significant downregulation of cyclins including CDK2, CDK4, and Cyclin D1 responsible for cell-cycle regulation. syringic acid 0-3 cyclin dependent kinase 2 Homo sapiens 62-66 33550184-1 2021 Over 50 tetrahydroindazoles were synthesized after 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1H-indazol-4(3aH)-one (3) was identified as a hit compound in a high throughput screen for inhibition of CDK2 in complex with cyclin A. tetrahydroindazoles 8-27 cyclin dependent kinase 2 Homo sapiens 217-221 33550184-1 2021 Over 50 tetrahydroindazoles were synthesized after 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1H-indazol-4(3aH)-one (3) was identified as a hit compound in a high throughput screen for inhibition of CDK2 in complex with cyclin A. 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1h-indazol-4(3ah)-one 51-133 cyclin dependent kinase 2 Homo sapiens 217-221 33579185-0 2021 Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma. Vanoxerine dihydrochloride 13-39 cyclin dependent kinase 2 Homo sapiens 45-53 33663368-0 2022 Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent, and Evaluation for CDK2 Inhibition Activity. benzimidazole 24-37 cyclin dependent kinase 2 Homo sapiens 90-94 33663368-6 2022 The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. Adenosine Triphosphate 86-89 cyclin dependent kinase 2 Homo sapiens 82-85 33663368-7 2022 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Imatinib Mesylate 82-90 cyclin dependent kinase 2 Homo sapiens 28-32 33484942-0 2021 Eco-friendly sequential one-pot synthesis, molecular docking, and anticancer evaluation of arylidene-hydrazinyl-thiazole derivatives as CDK2 inhibitors. arylidene-hydrazinyl-thiazole 91-120 cyclin dependent kinase 2 Homo sapiens 136-140 33484942-4 2021 Here the discovery and development of arylidene-hydrazinyl-thiazole as a potentially CDK2 inhibitors is described, including details of the design and successful synthesis of the series analogs (27a-r) using one-pot approach under eco-friendly ultrasound and microwave conditions. arylidene-hydrazinyl-thiazole 38-67 cyclin dependent kinase 2 Homo sapiens 85-89 33484942-7 2021 These derivatives displayed an outstanding CDK2 inhibitory potential with varying degree of inhibition in the range of IC50 0.35-1.49 muM when compared with the standard inhibitor roscovitine having an IC50 value 0.71 muM. Roscovitine 180-191 cyclin dependent kinase 2 Homo sapiens 43-47 33669811-0 2021 Fargesin Inhibits EGF-Induced Cell Transformation and Colon Cancer Cell Growth by Suppression of CDK2/Cyclin E Signaling Pathway. fargesin 0-8 cyclin dependent kinase 2 Homo sapiens 97-101 33669811-4 2021 We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. fargesin 22-30 cyclin dependent kinase 2 Homo sapiens 121-146 33669811-4 2021 We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. fargesin 22-30 cyclin dependent kinase 2 Homo sapiens 148-152 33860197-9 2021 MK-8776 and SRA737 exhibited similar off-target effects: higher concentrations demonstrated transient protection from growth inhibition, circumvented DNA damage, and prevented checkpoint abrogation, possibly due to inhibition of CDK2. MK-8776 0-7 cyclin dependent kinase 2 Homo sapiens 229-233 33860197-9 2021 MK-8776 and SRA737 exhibited similar off-target effects: higher concentrations demonstrated transient protection from growth inhibition, circumvented DNA damage, and prevented checkpoint abrogation, possibly due to inhibition of CDK2. SRA737 12-18 cyclin dependent kinase 2 Homo sapiens 229-233 33860197-11 2021 LY2606368-resistant cells still abrogated DNA damage-induced S phase arrest, which requires low CDK2 activity, whereas inappropriately high CDK2 activity is responsible for sensitivity to CHK1i alone. prexasertib 0-9 cyclin dependent kinase 2 Homo sapiens 96-100 33579185-3 2021 RESULTS: We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 muM for QGY7703and 4.04 muM for Huh7 cells). Vanoxerine dihydrochloride 23-49 cyclin dependent kinase 2 Homo sapiens 59-67 33579185-4 2021 In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Vanoxerine dihydrochloride 27-53 cyclin dependent kinase 2 Homo sapiens 132-140 33579185-4 2021 In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Vanoxerine dihydrochloride 27-53 cyclin dependent kinase 2 Homo sapiens 217-225 33579185-9 2021 Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. Vanoxerine dihydrochloride 120-145 cyclin dependent kinase 2 Homo sapiens 109-117 33579185-10 2021 CONCLUSIONS: The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment. Vanoxerine dihydrochloride 94-120 cyclin dependent kinase 2 Homo sapiens 68-76 33538198-9 2021 Furthermore, fenofibrate could significantly increase the expression of cell cycle related protein (CyclinD1, CDK2)and cell proliferation related proteins (PCNA). Fenofibrate 13-24 cyclin dependent kinase 2 Homo sapiens 110-114 33665254-1 2021 This article contains supplemental datasets of the recently published related research article "Synthesis, Inverse Docking-Assisted Identification and in vitro Biological Characterization of Flavonol-based Analogs of Fisetin as c-Kit, CDK2 and mTOR Inhibitors against Melanoma and Non-melanoma Skin Cancers" by Roy et al., [1]. 3-hydroxyflavone 191-199 cyclin dependent kinase 2 Homo sapiens 235-239 33450548-0 2021 Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers. 3-hydroxyflavone 95-103 cyclin dependent kinase 2 Homo sapiens 139-143 33517274-5 2021 Flow cytometry, western blotting, and caspase-3/7 assays revealed that CCL299 induced G1-phase cell-cycle arrest followed by apoptosis that was associated with up-regulation of p-p53 (Ser15) and p21 expression and the down-regulation of p-CDK2 (Thr160) expression. ccl299 71-77 cyclin dependent kinase 2 Homo sapiens 239-243 33450548-0 2021 Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers. fisetin 121-128 cyclin dependent kinase 2 Homo sapiens 139-143 33359023-3 2021 Besides, dioscin could inhibit the proliferation of Ishikawa cells by blocking the G0/G1 cell cycle through up-regulation of p16, p21, and p27 and down-regulation of cycle-cellular protein (Cyclin A/D/E) and cyclin-dependent kinase (CDK2/4/6). dioscin 9-16 cyclin dependent kinase 2 Homo sapiens 233-241 32885355-5 2021 Artesunate induced G1 phase arrest by downregulating cyclin D1/D2, CDK2/6 and c-Myc. Artesunate 0-10 cyclin dependent kinase 2 Homo sapiens 67-73 33421460-6 2021 The results showed that polysaccharides treatment inhibited the expression of Cyclin E, Cyclin A and CDK2 and up regulated the expression of P53. Polysaccharides 24-39 cyclin dependent kinase 2 Homo sapiens 101-105 33603824-5 2021 1,6,8-Trihydroxy-4-benzoyloxy-3-methylanthraquinone (23) revealed the most firm fitting with the active pockets of CDK-2 and MMP-13; meanwhile, variecolorin H alkaloid (14) showed the highest fitting within TOP-2 with G equals to -36.51 kcal/mole. 1,6,8-trihydroxy-4-benzoyloxy-3-methylanthraquinone 0-51 cyclin dependent kinase 2 Homo sapiens 115-120 33555529-10 2021 Moreover, miR-424-5p restoration in combination with Taxol treatment decreased the colony formation by regulating Oct-4 and led to G2 arrest via modulating Cdk-2 expression. Paclitaxel 53-58 cyclin dependent kinase 2 Homo sapiens 156-161 33152171-6 2021 Our data further revealed that DRP1 activation through serine 616 phosphorylation is regulated by ERK/AKT and CDK2 in lung adenocarcinoma cell lines. Serine 55-61 cyclin dependent kinase 2 Homo sapiens 110-114 33416149-7 2021 Following garcinol treatment the expression levels of p53 and p21 were increased, while the expression levels of CDK2, CDK4, cyclin D1 and cyclin B1 were gradually decreased in a dose-dependent manner in both ISH and HEC-1B cells. garcinol 10-18 cyclin dependent kinase 2 Homo sapiens 113-117 33603824-5 2021 1,6,8-Trihydroxy-4-benzoyloxy-3-methylanthraquinone (23) revealed the most firm fitting with the active pockets of CDK-2 and MMP-13; meanwhile, variecolorin H alkaloid (14) showed the highest fitting within TOP-2 with G equals to -36.51 kcal/mole. variecolorin h alkaloid 144-167 cyclin dependent kinase 2 Homo sapiens 115-120 33574763-0 2020 Osthole Alleviates Neointimal Hyperplasia in Balloon-Induced Arterial Wall Injury by Suppressing Vascular Smooth Muscle Cell Proliferation and Downregulating Cyclin D1/CDK4 and Cyclin E1/CDK2 Expression. osthol 0-7 cyclin dependent kinase 2 Homo sapiens 187-191 33516252-0 2021 The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex. Rubidium 40-42 cyclin dependent kinase 2 Homo sapiens 105-109 33503433-3 2021 In the absence of any changes in beta cell mass, maturity, or proliferation, genetic deletion of Cdk2 in adult beta cells enhanced insulin secretion from isolated islets and improved glucose tolerance in vivo. Glucose 183-190 cyclin dependent kinase 2 Homo sapiens 97-101 32451414-7 2021 RNA-sequencing analyses revealed that avasimibe suppressed the expression of CDK2, cyclin E1, CDK4, cyclin D, CDK1, cyclin B1, Aurora A, and PLK1, while induced the expression of p53, p21, p27, and GADD45A, which was validated by Western blot analysis. avasimibe 38-47 cyclin dependent kinase 2 Homo sapiens 77-81 33503433-4 2021 At the single beta cell level, CDK2 restricts insulin secretion by increasing KATP conductance, raising the set point for membrane depolarization in response to activation of the phosphoenolpyruvate (PEP) cycle with mitochondrial fuels. Phosphoenolpyruvate 179-198 cyclin dependent kinase 2 Homo sapiens 31-35 33503433-4 2021 At the single beta cell level, CDK2 restricts insulin secretion by increasing KATP conductance, raising the set point for membrane depolarization in response to activation of the phosphoenolpyruvate (PEP) cycle with mitochondrial fuels. Phosphoenolpyruvate 200-203 cyclin dependent kinase 2 Homo sapiens 31-35 33503433-5 2021 In parallel with reduced beta cell recruitment, CDK2 restricts oxidative glucose metabolism while promoting glucose-dependent amplification of insulin secretion. Glucose 73-80 cyclin dependent kinase 2 Homo sapiens 48-52 33503433-5 2021 In parallel with reduced beta cell recruitment, CDK2 restricts oxidative glucose metabolism while promoting glucose-dependent amplification of insulin secretion. Glucose 108-115 cyclin dependent kinase 2 Homo sapiens 48-52 33259807-12 2021 AMG900 decreased CDK2, CDK4, CDK6, cyclin D1 and cyclin D3 expression, whereas p18, p21 and p27 expression increased. N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine 0-6 cyclin dependent kinase 2 Homo sapiens 17-21 33477856-7 2021 Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. salicylanilide 29-43 cyclin dependent kinase 2 Homo sapiens 163-171 33466812-0 2021 A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights. Isatin 3-hydrazone 26-50 cyclin dependent kinase 2 Homo sapiens 6-10 33466812-2 2021 Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. 3-hydrazonoindolin-2- 93-114 cyclin dependent kinase 2 Homo sapiens 56-60 33466812-3 2021 METHODS: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. hi 5 48-52 cyclin dependent kinase 2 Homo sapiens 188-192 33466812-4 2021 RESULTS: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. hi 5 35-39 cyclin dependent kinase 2 Homo sapiens 60-64 33520087-4 2021 Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression. berbamine 14-23 cyclin dependent kinase 2 Homo sapiens 196-200 33035554-5 2021 At the same time, EPZ015666 regulated cell cycle related protein (P53, P21, P27, CDK2) expression. GSK3235025 18-27 cyclin dependent kinase 2 Homo sapiens 81-85 33248353-5 2021 Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (DeltaG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (DeltaG = -33.83 Kcal/mol). sulochrin 15-24 cyclin dependent kinase 2 Homo sapiens 114-119 33248353-5 2021 Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (DeltaG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (DeltaG = -33.83 Kcal/mol). Monochlorosulocrin 33-52 cyclin dependent kinase 2 Homo sapiens 114-119 33248353-5 2021 Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (DeltaG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (DeltaG = -33.83 Kcal/mol). sulochrin 43-52 cyclin dependent kinase 2 Homo sapiens 114-119 33390512-0 2021 Design and Synthesis of New CDK2 Inhibitors Containing Thiazolone and Thiazolthione Scafold with Apoptotic Activity. thiazolone 55-65 cyclin dependent kinase 2 Homo sapiens 28-32 33390512-0 2021 Design and Synthesis of New CDK2 Inhibitors Containing Thiazolone and Thiazolthione Scafold with Apoptotic Activity. thiazolthione 70-83 cyclin dependent kinase 2 Homo sapiens 28-32 33390512-4 2021 The novel thiazolone and the fused thiazolthione derivatives exhibited potent CDK2/cyclin A2 inhibitory effect of an IC50 values ranging 105.39-742.78 nM. thiazolone 10-20 cyclin dependent kinase 2 Homo sapiens 78-82 33390512-4 2021 The novel thiazolone and the fused thiazolthione derivatives exhibited potent CDK2/cyclin A2 inhibitory effect of an IC50 values ranging 105.39-742.78 nM. thiazolthione 35-48 cyclin dependent kinase 2 Homo sapiens 78-82 33390512-8 2021 Molecular modeling simulation of the designed compounds revealed that they were well fitted into CDK2 active site and their complexes were stabilized through the essential hydrogen bonding. Hydrogen 172-180 cyclin dependent kinase 2 Homo sapiens 97-101 33049687-3 2021 To this end, we evaluated eight synthetic flavones for their CDK2 binding by molecular docking. Flavones 42-50 cyclin dependent kinase 2 Homo sapiens 61-65 33049687-9 2021 Based on these data, the synthesized flavones might have clinical potential as potential inhibitors of CDK2. Flavones 37-45 cyclin dependent kinase 2 Homo sapiens 103-107 33248353-5 2021 Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (DeltaG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (DeltaG = -33.83 Kcal/mol). Diorcinol 0-9 cyclin dependent kinase 2 Homo sapiens 114-119 33248145-5 2021 In addition, western blotting assay revealed the increased expressions of the p53, Bax, caspase 3, and a reduction of Bcl-2 and CDK2, resulting in Se-TE-induced apoptosis. se-te 147-152 cyclin dependent kinase 2 Homo sapiens 128-132 33035554-6 2021 In brief, our study showed that PRMT5 promoted retinoblastoma growth, the PRMT5 inhibitor EPZ015666 inhibited retinoblastoma in vitro by regulating P53-P21/P27-CDK2 signaling pathways and slowed retinoblastoma growth in a xenograft model. GSK3235025 90-99 cyclin dependent kinase 2 Homo sapiens 160-164 33039146-8 2020 Furthermore, the accumulation of Cyclin Y could activate CDK4 through T172 phosphorylation of CDK4, inactivate Rb with increasing Rb phosphorylation, and enable the expression of E2F target genes such as CDK2 and Cyclin A. Rubidium 111-113 cyclin dependent kinase 2 Homo sapiens 204-208 33298132-0 2020 Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway. N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide 0-9 cyclin dependent kinase 2 Homo sapiens 146-150 33322048-5 2020 LCTP also induced the cell cycle arrest in G2/M phase, confirmed by decrease of CDK2 protein and increase of p53 and p21. intybin 0-4 cyclin dependent kinase 2 Homo sapiens 80-84 33298132-0 2020 Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway. Anthracyclines 94-108 cyclin dependent kinase 2 Homo sapiens 146-150 33298132-6 2020 We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. Anthracyclines 88-101 cyclin dependent kinase 2 Homo sapiens 32-36 33298132-9 2020 Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide 0-9 cyclin dependent kinase 2 Homo sapiens 167-171 33298132-9 2020 Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. Anthracyclines 39-52 cyclin dependent kinase 2 Homo sapiens 167-171 33298132-10 2020 CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application. N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide 12-21 cyclin dependent kinase 2 Homo sapiens 94-98 33298132-10 2020 CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application. Anthracyclines 35-48 cyclin dependent kinase 2 Homo sapiens 94-98 33414996-11 2020 High throughput signalling analysis showed that one cluster of stress-associated kinase proteins including p53, ROCK1 and JNK were suppressed, while the mitotic checkpoint protein-serine kinases CDK1 and CDK2 were activated, as a consequence of the DHX36 knockdown. Serine 180-186 cyclin dependent kinase 2 Homo sapiens 204-208 33292156-6 2021 The molecular docking of bilirubin on CDKs (Cyclin-dependent kinases 2, 4, and 6) and pro-apoptotic factors Bad, Bak, Bax, Bid, Bik, and Bim were done by Autodock software version 2. Bilirubin 25-34 cyclin dependent kinase 2 Homo sapiens 38-42 33292156-6 2021 The molecular docking of bilirubin on CDKs (Cyclin-dependent kinases 2, 4, and 6) and pro-apoptotic factors Bad, Bak, Bax, Bid, Bik, and Bim were done by Autodock software version 2. Bilirubin 25-34 cyclin dependent kinase 2 Homo sapiens 44-80 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide 162-171 cyclin dependent kinase 2 Homo sapiens 137-141 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide 162-171 cyclin dependent kinase 2 Homo sapiens 89-92 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. Cytarabine 172-177 cyclin dependent kinase 2 Homo sapiens 89-92 33344441-10 2020 Meanwhile, dasatinib also suppressed the expression of markers relating cell cycle, cyclin D1, D3, and CDK2, and increased the levels of markers involved in cell apoptosis, cleaved caspase-3 and caspase-7 by downregulating phosphorylated LIMK1 (p-LIMK1) and cofilin (p-cofilin). Dasatinib 11-20 cyclin dependent kinase 2 Homo sapiens 103-107 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide 14-23 cyclin dependent kinase 2 Homo sapiens 137-141 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide 14-23 cyclin dependent kinase 2 Homo sapiens 89-92 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. Cytarabine 28-33 cyclin dependent kinase 2 Homo sapiens 137-141 33276759-14 2020 Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. Cytarabine 28-33 cyclin dependent kinase 2 Homo sapiens 89-92 33287214-6 2020 In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. Arecoline 17-26 cyclin dependent kinase 2 Homo sapiens 144-148 33287214-8 2020 In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. Arecoline 16-25 cyclin dependent kinase 2 Homo sapiens 36-40 32986180-5 2020 Microarray assay, real-time PCR and western blot results revealed that AOS was able to effectively suppress H2O2-induced apoptosis via regulated integrin-alpha/FAK/PI3K pathway by influencing the expression of integrin-alpha, FAK, PI3K, PTEN, P21, and CDK2. Hydrogen Peroxide 108-112 cyclin dependent kinase 2 Homo sapiens 252-256 32693671-5 2020 Reverse transcription polymerase chain reaction analysis showed significant inhibition of Cyclin-dependent kinases (CDK)4/6-cyclin D and CDK2-cyclin-E expression upon treatment with a low concentration PIP-TMZ, suggesting an S to G1 arrest. pip-tmz 202-209 cyclin dependent kinase 2 Homo sapiens 137-141 33048473-11 2020 Pharmacological analysis showed that the administration of two cell cycle inhibitors for inactivating CDC25A phosphatase (NSC95397) and the cyclin E2/cyclin-dependent kinase 2 (CDK2) complex (purvalanol A) increased the dome number independently of MTA. purvalanol B 192-202 cyclin dependent kinase 2 Homo sapiens 177-181 31760818-1 2020 Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. seryl-seryl-seryl-arginine 50-53 cyclin dependent kinase 2 Homo sapiens 0-25 33225729-8 2020 Conclusion: Tropane/pyran scaffold can be considered as a promising core for anticancer agents acting as CDK2 inhibitors. Tropanes 12-19 cyclin dependent kinase 2 Homo sapiens 105-109 33225729-8 2020 Conclusion: Tropane/pyran scaffold can be considered as a promising core for anticancer agents acting as CDK2 inhibitors. Pyrans 20-25 cyclin dependent kinase 2 Homo sapiens 105-109 32522063-0 2020 Novel [(N-alkyl-3-indolylmethylene)hydrazono]oxindoles arrest cell cycle and induce cell apoptosis by inhibiting CDK2 and Bcl-2: synthesis, biological evaluation and in silico studies. [(n-alkyl-3-indolylmethylene)hydrazono]oxindoles 6-54 cyclin dependent kinase 2 Homo sapiens 113-117 31760818-1 2020 Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. seryl-seryl-seryl-arginine 50-53 cyclin dependent kinase 2 Homo sapiens 27-31 31760818-1 2020 Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. peptide T amide 54-57 cyclin dependent kinase 2 Homo sapiens 0-25 31760818-1 2020 Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. peptide T amide 54-57 cyclin dependent kinase 2 Homo sapiens 27-31 33098638-0 2020 Cross-talk between the ER pathway and the lncRNA MAFG-AS1/miR-339-5p/ CDK2 axis promotes progression of ER+ breast cancer and confers tamoxifen resistance. Tamoxifen 134-143 cyclin dependent kinase 2 Homo sapiens 70-74 33027592-7 2020 In addition, aaptamine arrested cell cycle at G1 phase via selectively abating cell cycle regulation drivers (CDK2/4 and Cyclin D1/E). aaptamine 13-22 cyclin dependent kinase 2 Homo sapiens 110-116 32980991-13 2020 Interfering lncPCAT19/overexpression of miR-142-5p decreased glioma cell proliferation, colony formation and invasion, and promoted cell apoptosis by down-regulating expression of Cyclin B1, CDK2, N-cadherin, Bcl-2, and by up-regulating expression of Bax and E-cadherin. mir-142-5p 40-50 cyclin dependent kinase 2 Homo sapiens 191-195 32854577-11 2020 Three key targets (CDK2, ESR1 and CDK1) involving 1766 proteins become the multi-targets mechanism of HCQ in the treatment of SLE. Hydroxychloroquine 102-105 cyclin dependent kinase 2 Homo sapiens 19-23 33100862-10 2020 Molecular dynamic simulation studies have further confirmed the finding of docking analysis, suggesting that CDK2 and TS can act as an attractive molecular target for BAN and CBT, respectively. cyclobarbital 175-178 cyclin dependent kinase 2 Homo sapiens 109-113 32781872-0 2020 Discovery of 3,6-disubstituted pyridazines as a novel class of anticancer agents targeting cyclin-dependent kinase 2: synthesis, biological evaluation and in silico insights. 3,6-disubstituted 13-30 cyclin dependent kinase 2 Homo sapiens 91-116 32781872-0 2020 Discovery of 3,6-disubstituted pyridazines as a novel class of anticancer agents targeting cyclin-dependent kinase 2: synthesis, biological evaluation and in silico insights. Pyridazines 31-42 cyclin dependent kinase 2 Homo sapiens 91-116 32781872-8 2020 Furthermore, an in silico study proposed CDK2 as a probable enzymatic target for pyridazines 11, and explored their binding interactions within the vicinity of CDK2 binding site. Pyridazines 81-92 cyclin dependent kinase 2 Homo sapiens 41-45 32781872-8 2020 Furthermore, an in silico study proposed CDK2 as a probable enzymatic target for pyridazines 11, and explored their binding interactions within the vicinity of CDK2 binding site. Pyridazines 81-92 cyclin dependent kinase 2 Homo sapiens 160-164 32781872-9 2020 Subsequently, pyridazines 11e, 11h, 11l, and 11m were selected to be evaluated for their ability to inhibit CDK2, where they exerted good inhibitory activity (IC50 = 151, 43.8, 55.6 and 20.1 nM, respectively). Pyridazines 14-25 cyclin dependent kinase 2 Homo sapiens 108-112 32781872-11 2020 Overall the obtained results from this study quite sustained our strategy and gave us a robust opportunity for further development and optimisation of 3,6-disubstituted pyridazine scaffold to enrich therapeutic arsenal with efficient and safe anticancer CDK inhibitors. 3,6-disubstituted 151-168 cyclin dependent kinase 2 Homo sapiens 254-257 32781872-11 2020 Overall the obtained results from this study quite sustained our strategy and gave us a robust opportunity for further development and optimisation of 3,6-disubstituted pyridazine scaffold to enrich therapeutic arsenal with efficient and safe anticancer CDK inhibitors. pyridazine 169-179 cyclin dependent kinase 2 Homo sapiens 254-257 32911016-2 2020 This study was undertaken to verify whether E2 action in human osteoblasts involves changes in the transcriptional profile of the TNF-alpha, IFN-gamma, NF-kappaB, TRAIL, TGF-beta, MMP2, MMP9, RECK, TIMP1, TIMP2, CDK2, CDK4, SRC, RUNX2, and SHH genes. Estradiol 44-46 cyclin dependent kinase 2 Homo sapiens 212-216 33059240-7 2020 Furthermore, miR-506-3p could also suppress the expression of CDK2/Cyclin E1 compound which could be affected by YAP1 gene. mir-506-3p 13-23 cyclin dependent kinase 2 Homo sapiens 62-66 33059240-8 2020 Therefore miR-506-3p might have proliferation-suppressive function in PTC by inhibiting YAP1 expression and regulating YAP1-CDK2/Cy clin E1 cell cycle pathway. mir-506-3p 10-20 cyclin dependent kinase 2 Homo sapiens 124-128 33016930-2 2020 Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CYC065 27-38 cyclin dependent kinase 2 Homo sapiens 74-78 33073770-4 2020 In addition, MHY2256 induced G0/G1 phase arrest of the cell cycle progression, which was accompanied by the reduction of cyclin D1 and cyclin E and the decrease of cyclin-dependent kinase 2, cyclin-dependent kinase 4, cyclin-dependent kinase 6, phosphorylated retinoblastoma protein, and E2F transcription factor 1. mhy2256 13-20 cyclin dependent kinase 2 Homo sapiens 164-189 32854577-7 2020 RESULTS: The results suggest that the efficacy of HCQ against SLE is mainly associated with the targets of cyclin-dependent kinase 2 (CDK2), estrogen receptor alpha (ESR1) and CDK1, which regulate PI3K/Akt/GSK3beta as well as interferon (IFN) signaling pathway. Hydroxychloroquine 50-53 cyclin dependent kinase 2 Homo sapiens 107-132 32854577-7 2020 RESULTS: The results suggest that the efficacy of HCQ against SLE is mainly associated with the targets of cyclin-dependent kinase 2 (CDK2), estrogen receptor alpha (ESR1) and CDK1, which regulate PI3K/Akt/GSK3beta as well as interferon (IFN) signaling pathway. Hydroxychloroquine 50-53 cyclin dependent kinase 2 Homo sapiens 134-138 33116269-0 2020 Dinaciclib, a cyclin-dependent kinase inhibitor, suppresses cholangiocarcinoma growth by targeting CDK2/5/9. dinaciclib 0-10 cyclin dependent kinase 2 Homo sapiens 99-107 33098638-8 2020 Subsequently, MAFG-AS1 and CDK2 were found to be up-regulated in tamoxifen-resistant MCF-7 cells. Tamoxifen 65-74 cyclin dependent kinase 2 Homo sapiens 27-31 33098638-9 2020 Cross-talk between the ER signaling pathway and cell cycle conducted by MAFG-AS1 and CDK2 could promote tamoxifen resistance. Tamoxifen 104-113 cyclin dependent kinase 2 Homo sapiens 85-89 33086722-8 2020 Western blot analysis showed that treatment with a low concentration of AXT upregulated cyclin-dependent kinase (Cdk) 2 and p-Cdk2/3 levels and downregulated the expression of tumor protein p53. astaxanthine 72-75 cyclin dependent kinase 2 Homo sapiens 88-119 33086722-8 2020 Western blot analysis showed that treatment with a low concentration of AXT upregulated cyclin-dependent kinase (Cdk) 2 and p-Cdk2/3 levels and downregulated the expression of tumor protein p53. astaxanthine 72-75 cyclin dependent kinase 2 Homo sapiens 126-132 32820789-2 2020 Thus, in a model study, we investigated the meso-methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. meso-methyl-bodipy 44-62 cyclin dependent kinase 2 Homo sapiens 69-73 32820789-2 2020 Thus, in a model study, we investigated the meso-methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. AZD5438 84-91 cyclin dependent kinase 2 Homo sapiens 69-73 32820789-2 2020 Thus, in a model study, we investigated the meso-methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 56-62 cyclin dependent kinase 2 Homo sapiens 69-73 33101585-8 2020 Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. phillyrin 0-9 cyclin dependent kinase 2 Homo sapiens 61-86 33101585-8 2020 Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. phillyrin 0-9 cyclin dependent kinase 2 Homo sapiens 88-92 32992673-0 2020 A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor. Adenosine Triphosphate 111-114 cyclin dependent kinase 2 Homo sapiens 58-62 32945504-7 2020 We also found that combined treatment of Rg3 and 5-FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. Fluorouracil 49-53 cyclin dependent kinase 2 Homo sapiens 270-274 32992673-0 2020 A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor. isatin-hydrazones 12-29 cyclin dependent kinase 2 Homo sapiens 58-62 33050377-5 2020 Our results of network and pathway analysis of the 12 samples highlighted the importance of VEGFR and CDKs in promoting luminal-A breast cancer. Phenobarbital 120-127 cyclin dependent kinase 2 Homo sapiens 102-106 33050377-10 2020 Interestingly, HAA2020 and dinaciclib showed a synergistic apoptotic and G1 cell cycle effect in MCF7 cells, which was supported by their synergistic CDK2, cyclin D1, and PCNA inhibition activities. dinaciclib 27-37 cyclin dependent kinase 2 Homo sapiens 150-154 30887847-5 2020 Results were further supported by in-silico molecular docking of pulchranin A to CDK1, CDK2, and CDK4 crystal structures, where it demonstrated good interactions by H-bonding, hydrophobic and Pi-Pi interactions with different amino acid residues of these enzymes. pulchranin a 65-77 cyclin dependent kinase 2 Homo sapiens 87-91 32945504-7 2020 We also found that combined treatment of Rg3 and 5-FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. ginsenoside Rg3 41-44 cyclin dependent kinase 2 Homo sapiens 270-274 33824124-8 2020 Furthermore, CDK2 levels were markedly increased in hypoxic cells (P<0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P<0.05). 3,4-dihydroxyacetophenone 82-86 cyclin dependent kinase 2 Homo sapiens 115-119 32930901-16 2020 The compounds designed were more active than the template and showed better inhibition of the CDK2 enzyme compared to the standard drugs sorafenib and kenpaullone. Sorafenib 137-146 cyclin dependent kinase 2 Homo sapiens 94-98 32930901-16 2020 The compounds designed were more active than the template and showed better inhibition of the CDK2 enzyme compared to the standard drugs sorafenib and kenpaullone. kenpaullone 151-162 cyclin dependent kinase 2 Homo sapiens 94-98 32364649-3 2020 Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3. Dictyodendrin 5-18 cyclin dependent kinase 2 Homo sapiens 68-72 31784978-10 2020 In support, data from q-RT PCR showed that SCFA treatments influenced the expression of the neurogenesis, proliferation, and apoptosis-related genes ATR, BCL2, BID, CASP8, CDK2, E2F1, FAS, NDN, and VEGFA. Fatty Acids, Volatile 43-47 cyclin dependent kinase 2 Homo sapiens 172-176 32899250-6 2020 CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Rubidium 14-16 cyclin dependent kinase 2 Homo sapiens 0-4 32899250-6 2020 CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. abemaciclib 107-118 cyclin dependent kinase 2 Homo sapiens 0-4 32872665-5 2020 In addition, CD treatment led to cell cycle arrest at the G0/G1 phase and inhibited expression of cyclin D1 and cyclin-dependent kinases 2 and 4 and led to increased levels of p21, p27Kip1 and p53. Cadmium 13-15 cyclin dependent kinase 2 Homo sapiens 112-144 32419149-9 2020 14,15beta-dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p-CDK2, cyclin B1, p21, E2F-1 and PCNA. 14,15beta-dihydroxyklaineanone 0-30 cyclin dependent kinase 2 Homo sapiens 114-118 31498033-0 2020 Molecular dynamics simulations reveal the determinants of cyclin-dependent kinase 2 inhibition by 5-nitrosopyrimidine derivatives. 5-Nitrosopyrimidine 98-117 cyclin dependent kinase 2 Homo sapiens 58-83 32744246-1 2020 CVT-313 is a potent CDK2 inhibitor that was identified by screening a purine-analogue library and is currently in preclinical studies. purine 70-76 cyclin dependent kinase 2 Homo sapiens 20-24 32744246-6 2020 The crystal structure of CDK2 bound to CVT-313 was determined to a resolution of 1.74 A and clearly demonstrated that CVT-313 binds in the ATP-binding pocket, interacting with Leu83, Asp86 and Asp145 directly, and the binding was further stabilized by a water-mediated interaction with Asn132. Adenosine Triphosphate 139-142 cyclin dependent kinase 2 Homo sapiens 25-29 32744246-6 2020 The crystal structure of CDK2 bound to CVT-313 was determined to a resolution of 1.74 A and clearly demonstrated that CVT-313 binds in the ATP-binding pocket, interacting with Leu83, Asp86 and Asp145 directly, and the binding was further stabilized by a water-mediated interaction with Asn132. Water 254-259 cyclin dependent kinase 2 Homo sapiens 25-29 32915362-11 2020 The increase in berberine concentration led to an increase in miRNA-582-5p and miRNA-188-5p expression and a decrease in the expression of mRNA for the corresponding target genes encoding CDK1, CDK2, and cyclins D1 and A. Berberine 16-25 cyclin dependent kinase 2 Homo sapiens 194-198 32415712-2 2020 Development of CDK2 inhibitors has been extremely challenging as its ATP-binding site shares high similarity with CDK1, a related kinase whose inhibition causes toxic effects. Adenosine Triphosphate 69-72 cyclin dependent kinase 2 Homo sapiens 15-19 31498033-10 2020 The biophysical insight obtained through state-of-the-art simulations enabled a deeper understanding of the structure-activity relationships of nitrosopyrimidine CDK2 inhibitors and gave new hints for the design of new molecules belonging to this class. 2-Nitrosopyrimidine 144-161 cyclin dependent kinase 2 Homo sapiens 162-166 32691623-0 2021 Inhibition of CDK2/CyclinE1 by xanthones from the mangosteen (Garcinia mangostana): a structure-activity relationship study. Xanthones 31-40 cyclin dependent kinase 2 Homo sapiens 14-18 32212222-0 2020 Optimization of norbornyl-based carbocyclic nucleoside analogs as cyclin-dependent kinase 2 inhibitors. norbornyl 16-25 cyclin dependent kinase 2 Homo sapiens 66-91 32212222-0 2020 Optimization of norbornyl-based carbocyclic nucleoside analogs as cyclin-dependent kinase 2 inhibitors. carbocyclic nucleoside 32-54 cyclin dependent kinase 2 Homo sapiens 66-91 32212222-1 2020 We report on the discovery of norbornyl moiety as a novel structural motif for cyclin-dependent kinase 2 (CDK2) inhibitors which was identified by screening a carbocyclic nucleoside analogue library. norbornyl 30-39 cyclin dependent kinase 2 Homo sapiens 79-104 32212222-1 2020 We report on the discovery of norbornyl moiety as a novel structural motif for cyclin-dependent kinase 2 (CDK2) inhibitors which was identified by screening a carbocyclic nucleoside analogue library. norbornyl 30-39 cyclin dependent kinase 2 Homo sapiens 106-110 32212222-1 2020 We report on the discovery of norbornyl moiety as a novel structural motif for cyclin-dependent kinase 2 (CDK2) inhibitors which was identified by screening a carbocyclic nucleoside analogue library. carbocyclic nucleoside 159-181 cyclin dependent kinase 2 Homo sapiens 79-104 32212222-1 2020 We report on the discovery of norbornyl moiety as a novel structural motif for cyclin-dependent kinase 2 (CDK2) inhibitors which was identified by screening a carbocyclic nucleoside analogue library. carbocyclic nucleoside 159-181 cyclin dependent kinase 2 Homo sapiens 106-110 32212222-6 2020 In conclusion, the discovered 9-hydroxymethylnorbornyl moiety was shown by joint experimental-theoretical efforts to be able to serve as a novel substituent for CDK2 inhibitors. 9-hydroxymethylnorbornyl 30-54 cyclin dependent kinase 2 Homo sapiens 161-165 32712628-5 2020 Here, we report that RRM1 is phosphorylated at Ser 559 by CDK2/cyclin A during S/G2 phase. Serine 47-50 cyclin dependent kinase 2 Homo sapiens 58-62 32691623-2 2021 Herein we present data reporting that xanthones, a class of compounds isolated from the purple mangosteen (Garcinia mangostana) fruit, can inhibit CDK2/CyclinE1. Xanthones 38-47 cyclin dependent kinase 2 Homo sapiens 147-151 32691623-8 2021 Taken together, the evidence suggests that xanthones can directly target CDK2 providing a possible explanation for their therapeutic potential. Xanthones 43-52 cyclin dependent kinase 2 Homo sapiens 73-77 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. dinaciclib 87-97 cyclin dependent kinase 2 Homo sapiens 71-75 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. dinaciclib 87-97 cyclin dependent kinase 2 Homo sapiens 157-161 32433863-0 2020 Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2. 8-anilino-1-naphthalenesulfonic acid 70-107 cyclin dependent kinase 2 Homo sapiens 117-142 32433863-0 2020 Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2. 8-anilino-1-naphthalenesulfonic acid 109-112 cyclin dependent kinase 2 Homo sapiens 117-142 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. Roscovitine 102-113 cyclin dependent kinase 2 Homo sapiens 71-75 32433863-2 2020 We have previously discovered that 8-anilino-1-naphthalene sulfonic acid (ANS) binds an allosteric pocket in cyclin-dependent kinase 2 (Cdk2). 8-anilino-1-naphthalenesulfonic acid 35-72 cyclin dependent kinase 2 Homo sapiens 109-134 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. Roscovitine 102-113 cyclin dependent kinase 2 Homo sapiens 157-161 32433863-2 2020 We have previously discovered that 8-anilino-1-naphthalene sulfonic acid (ANS) binds an allosteric pocket in cyclin-dependent kinase 2 (Cdk2). 8-anilino-1-naphthalenesulfonic acid 35-72 cyclin dependent kinase 2 Homo sapiens 136-140 32433863-2 2020 We have previously discovered that 8-anilino-1-naphthalene sulfonic acid (ANS) binds an allosteric pocket in cyclin-dependent kinase 2 (Cdk2). 8-anilino-1-naphthalenesulfonic acid 74-77 cyclin dependent kinase 2 Homo sapiens 109-134 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. 8-anilino-1-naphthalenesulfonic acid 146-149 cyclin dependent kinase 2 Homo sapiens 71-75 32433863-2 2020 We have previously discovered that 8-anilino-1-naphthalene sulfonic acid (ANS) binds an allosteric pocket in cyclin-dependent kinase 2 (Cdk2). 8-anilino-1-naphthalenesulfonic acid 74-77 cyclin dependent kinase 2 Homo sapiens 136-140 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. 8-anilino-1-naphthalenesulfonic acid 146-149 cyclin dependent kinase 2 Homo sapiens 157-161 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. 8-anilino-1-naphthalenesulfonic acid 51-54 cyclin dependent kinase 2 Homo sapiens 157-161 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. Adenosine Triphosphate 226-229 cyclin dependent kinase 2 Homo sapiens 71-75 32433863-3 2020 Here, we detail the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increase the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. Adenosine Triphosphate 226-229 cyclin dependent kinase 2 Homo sapiens 157-161 32506967-5 2022 BaP significantly increased the proportions of cells in S and G2/M phases, with concomitant reductions in the proportions of cells in G0/G1 phase, following 5 and 25 microM exposure, which was accompanied by the upregulation of the regulatory proteins cyclin A, cyclin B, cyclin-dependent kinase (CDK)1, and CDK2. Benzo(a)pyrene 0-3 cyclin dependent kinase 2 Homo sapiens 308-312 32032659-0 2020 Roscovitine enhances All-trans retinoic acid (ATRA)-induced leukemia cell differentiation: Novel effects on signaling molecules for a putative Cdk2 inhibitor. roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 143-147 32032659-0 2020 Roscovitine enhances All-trans retinoic acid (ATRA)-induced leukemia cell differentiation: Novel effects on signaling molecules for a putative Cdk2 inhibitor. Tretinoin 46-50 cyclin dependent kinase 2 Homo sapiens 143-147 32423798-11 2020 Mutation of two critical catalyzing amino acid residues (p.H88A and p.D89A) abrogated the capability of PLA2G10 to catalyze the production of arachidonic acid (AA), and also canceled the regulatory effects on cyclin E1 and CDK2 expression, as well as G1/S transition. Arachidonic Acid 142-158 cyclin dependent kinase 2 Homo sapiens 223-227 32606957-12 2020 Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. gemcitabine 10-21 cyclin dependent kinase 2 Homo sapiens 83-87 32606957-12 2020 Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. pitavastatin 22-34 cyclin dependent kinase 2 Homo sapiens 83-87 32304943-6 2020 In addition, TDCPP induced cell apoptosis and arrested cell cycle in the G0/G1 phase at 16 and 160 mug/mL by enhancing Bax and Caspase-3 expression besides inhibiting cyclin D1, CDK2, CDK6 and Bcl-2 expression. tris(1,3-dichloro-2-propyl)phosphate 13-18 cyclin dependent kinase 2 Homo sapiens 178-182 32645016-0 2020 Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer. CYC065 0-11 cyclin dependent kinase 2 Homo sapiens 30-33 32645016-12 2020 Fadraciclib preclinical pharmacology data support its therapeutic potential in CDK9- or CDK2-dependent cancers and as a rational combination with BCL2 inhibitors in hematological malignancies. CYC065 0-11 cyclin dependent kinase 2 Homo sapiens 88-92 32555680-5 2020 Furthermore, Western blot analysis revealed that PD173074 decreased the levels of P-FRS2alpha, P-ERK, CDK2, cyclin E and NF-kappaB (p65) in the nucleus while it increased the levels of ubiquitin and CUL3, an E3 ubiquitin ligase which involves in cyclin E degradation. PD 173074 49-57 cyclin dependent kinase 2 Homo sapiens 102-106 32236634-3 2020 HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. hs-146 0-6 cyclin dependent kinase 2 Homo sapiens 177-207 32307447-3 2020 Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression of EGFR, MAPK, CDK4, CDK2, CDK7, CCNE1 and CCNE2. palbociclib 14-25 cyclin dependent kinase 2 Homo sapiens 125-129 31112603-4 2020 We demonstrate that the selective cytotoxicity of the combination, called CucWi-N, to cancer cells is mediated by induction of cellular senescence that was characterized by decrease in Lamin A/C, CDK2, CDK4, Cyclin D, Cyclin E, phosphorylated RB, mortalin and increase in p53 and CARF proteins. cucwi-n 74-81 cyclin dependent kinase 2 Homo sapiens 196-200 32494624-2 2020 We used an "in situ" approach to identify CDK2 substrates within nuclei isolated from cells expressing CDK2 engineered to use adenosine 5"-triphosphate analogs. Adenosine 126-135 cyclin dependent kinase 2 Homo sapiens 42-46 32041019-7 2020 CDK1 and cyclin B, two G2/M cycle-related proteins, and CDK2, a G0/G1 cycle-related protein, were reduced in 1-NP-exposed trophoblasts. 1-nitropyrene 109-113 cyclin dependent kinase 2 Homo sapiens 56-60 32041019-8 2020 Phosphorylated Rb, a downstream molecule of CDK2, was inhibited in 1-NP-exposed trophoblasts. Rubidium 15-17 cyclin dependent kinase 2 Homo sapiens 44-48 32041019-8 2020 Phosphorylated Rb, a downstream molecule of CDK2, was inhibited in 1-NP-exposed trophoblasts. 1-nitropyrene 67-71 cyclin dependent kinase 2 Homo sapiens 44-48 32062191-3 2020 Here we found that rapamycin inhibited human soluble BAFF (hsBAFF)-stimulated cell proliferation by inducing G1-cell cycle arrest, which was through downregulating the protein levels of CDK2, CDK4, CDK6, cyclin A, cyclin D1, and cyclin E. Rapamycin reduced hsBAFF-stimulated cell survival by downregulating the levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xL and survivin) and meanwhile upregulating the levels of pro-apoptotic proteins (BAK and BAX). Sirolimus 19-28 cyclin dependent kinase 2 Homo sapiens 186-190 32323807-6 2020 In addition, alpha-solanine arrested the cell cycle at the G0/G1 phase and suppressed the expression levels of cyclin D1 and cyclin-dependent kinase 2 in RKO cells. alpha-solanine 13-27 cyclin dependent kinase 2 Homo sapiens 125-150 32494624-2 2020 We used an "in situ" approach to identify CDK2 substrates within nuclei isolated from cells expressing CDK2 engineered to use adenosine 5"-triphosphate analogs. Adenosine 126-135 cyclin dependent kinase 2 Homo sapiens 103-107 32252280-11 2020 The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. bis-indoles 87-98 cyclin dependent kinase 2 Homo sapiens 110-114 32036474-4 2020 Western blot analysis with an antibody to gammaH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which correlated with decreased levels in Cyclin A, Cyclin B, Cyclin D1 and cyclin dependent kinase 2 and an increase in levels of the cyclin dependent kinase inhibitor p21. ds00329 64-71 cyclin dependent kinase 2 Homo sapiens 258-283 32368395-1 2020 The cyclin-dependent kinase 2 (CDK2) inhibitor dinaciclib, a potential anti-cancer drug, has been tested in clinical trials and reported to suppress tumor initiating cells. dinaciclib 47-57 cyclin dependent kinase 2 Homo sapiens 4-29 32368395-1 2020 The cyclin-dependent kinase 2 (CDK2) inhibitor dinaciclib, a potential anti-cancer drug, has been tested in clinical trials and reported to suppress tumor initiating cells. dinaciclib 47-57 cyclin dependent kinase 2 Homo sapiens 31-35 32368395-2 2020 Our recent study demonstrated that pharmacological inhibition of CDK2 or enhancer of zeste homolog 2 (EZH2) allows re-expression of ERalpha and converts triple-negative breast cancers (TNBC) to luminal ERalpha-positive, rendering TNBC cells targetable by tamoxifen. Tamoxifen 255-264 cyclin dependent kinase 2 Homo sapiens 65-69 31911242-7 2020 The identified sites are shown to recapitulate the location of known drug-like molecules in both allosteric and orthosteric binding sites on seven proteins including the androgen receptor, the CDK2 and Erk5 kinases, PTP1B phosphatase and three GPCRs; the beta2-adrenergic, GPR40 fatty-acid binding and M2-muscarinic receptors. Fatty Acids 279-289 cyclin dependent kinase 2 Homo sapiens 193-197 31954769-5 2020 Moreover, MVC inhibited the cell cycle by down regulating the proteins of the complexes of cyclin dependent kinase (CDK) 4/6 - Cyclin D and CDK2 - Cyclin E, as well as by increasing the protein levels of CDK inhibitors p18, p21 and p27. maraviroc 10-13 cyclin dependent kinase 2 Homo sapiens 140-144 32104190-8 2020 Among them, alpha-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. alpha-viniferin 12-27 cyclin dependent kinase 2 Homo sapiens 88-92 31529315-4 2020 Protein expression of phosphorylated CDK2 (p-CDK2) in paraffin-embedded tissue specimens of ACC from 17 patients was investigated by immunohistochemistry (IHC). Paraffin 54-62 cyclin dependent kinase 2 Homo sapiens 37-41 31529315-4 2020 Protein expression of phosphorylated CDK2 (p-CDK2) in paraffin-embedded tissue specimens of ACC from 17 patients was investigated by immunohistochemistry (IHC). Paraffin 54-62 cyclin dependent kinase 2 Homo sapiens 45-49 31529315-9 2020 Moreover, it sensitized cells to the chemotherapeutic agents such as cisplatin, pemetrexed, and etoposide (VP-16), and this effect by dinaciclib may induce cell cycle arrest via abrogating CDK2 activity. Etoposide 96-105 cyclin dependent kinase 2 Homo sapiens 189-193 31529315-9 2020 Moreover, it sensitized cells to the chemotherapeutic agents such as cisplatin, pemetrexed, and etoposide (VP-16), and this effect by dinaciclib may induce cell cycle arrest via abrogating CDK2 activity. dinaciclib 134-144 cyclin dependent kinase 2 Homo sapiens 189-193 31816347-6 2020 The Fe-complex treatment caused cell cycle arrest via the activation of ATM-ATR kinase mediated DNA damage response pathway with the compromised expression of CDK1, CDK2 and CyclinB1 protein in Trigonella seedlings. Iron 4-6 cyclin dependent kinase 2 Homo sapiens 165-169 31972394-6 2020 Pyrazolopyrimidines 9d, 9e and 10b displayed weak CDK2 inhibitory activity (IC50 = 6.4, 8.0 and 11.6 muM, respectively), along with abolished CDK9 inhibitory activity. pyrazolopyrimidines 0-19 cyclin dependent kinase 2 Homo sapiens 50-54 31972394-7 2020 This trend suggested that pyrazolopyrimidine derivatives merit further optimization to furnish more effective CDK2 inhibitor lead. 1H-pyrazolo[4,3-d]pyrimidine 26-44 cyclin dependent kinase 2 Homo sapiens 110-114 32210718-10 2020 Western blot analysis showed that adenine reduced expression of cyclin A/D1 and cyclin-dependent kinase (CDK)2 and upregulated p53, p21, Bax, PUMA, and NOXA in HepG2 cell. Adenine 34-41 cyclin dependent kinase 2 Homo sapiens 80-110 32075913-0 2020 Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. Doxorubicin 0-11 cyclin dependent kinase 2 Homo sapiens 64-89 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Anthracyclines 31-44 cyclin dependent kinase 2 Homo sapiens 121-146 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Anthracyclines 31-44 cyclin dependent kinase 2 Homo sapiens 148-152 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Doxorubicin 46-57 cyclin dependent kinase 2 Homo sapiens 121-146 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Doxorubicin 46-57 cyclin dependent kinase 2 Homo sapiens 148-152 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Doxorubicin 59-62 cyclin dependent kinase 2 Homo sapiens 121-146 32075913-3 2020 We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). Doxorubicin 59-62 cyclin dependent kinase 2 Homo sapiens 148-152 32075913-5 2020 Here we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its proapoptotic target gene, Bcl-2-interacting mediator of cell death (Bim). Doxorubicin 25-28 cyclin dependent kinase 2 Homo sapiens 46-50 32075913-5 2020 Here we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its proapoptotic target gene, Bcl-2-interacting mediator of cell death (Bim). Serine 132-135 cyclin dependent kinase 2 Homo sapiens 46-50 32075913-9 2020 In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Doxorubicin 15-18 cyclin dependent kinase 2 Homo sapiens 36-40 32395375-0 2020 Protein Phosphatase 1H, Cyclin-Dependent Kinase Inhibitor p27, and Cyclin-Dependent Kinase 2 in Paclitaxel Resistance for Triple Negative Breast Cancers. Paclitaxel 96-106 cyclin dependent kinase 2 Homo sapiens 67-92 32395375-12 2020 The use of dinaciclib, a selective CDK inhibitor, significantly inhibited tumor growth in the PDX model. dinaciclib 11-21 cyclin dependent kinase 2 Homo sapiens 35-38 31435642-10 2020 Further investigations confirmed a role of IGF-I in preserving G1/S progression of CoCl2-treated GCs via activating the cyclin E/CDK2 complex through the PI3K/AKT/FOXO1/Cdkn1b axis. cobaltous chloride 83-88 cyclin dependent kinase 2 Homo sapiens 129-133 32104190-9 2020 In vitro, experimental data showed a nonnecrotic growth limitation of K562 cells caused by alpha-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. alpha-viniferin 91-106 cyclin dependent kinase 2 Homo sapiens 167-171 32104190-10 2020 mug mL-1 at 24 h. Finally, we validated the chemotherapeutic effect of alpha-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. alpha-viniferin 71-86 cyclin dependent kinase 2 Homo sapiens 147-151 32104190-12 2020 This work also predicts and validates targets in the mitochondrial signaling pathway, providing a novel strategy for CML treatment.alpha-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. alpha-viniferin 131-146 cyclin dependent kinase 2 Homo sapiens 207-211 31958895-3 2020 In addition, PBSA inhibited mitogen-induced cell proliferation by suppression of cyclin-dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. ensulizole 13-17 cyclin dependent kinase 2 Homo sapiens 107-111 31958895-4 2020 These anti-cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen-activated protein kinase kinase 3/6-p38 mitogen-activated protein kinase (MKK3/6-p38MAPK ) activity and subsequent down-regulation of MMP-2, MMP-9, Cdk4, Cdk2 and integrin beta1, as evidenced by treatment with p38MAPK inhibitor SB203580. ensulizole 32-36 cyclin dependent kinase 2 Homo sapiens 284-288 31883767-0 2020 Icariside II inhibits tumorigenesis via inhibiting AKT/Cyclin E/ CDK 2 pathway and activating mitochondria-dependent pathway. baohuoside I 0-12 cyclin dependent kinase 2 Homo sapiens 65-70 32476373-6 2020 After the treatment of 20 mumol/L of Rg5 for 24 h, Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex production and increasing the P21CIPI. rg5 37-40 cyclin dependent kinase 2 Homo sapiens 153-157 32476373-6 2020 After the treatment of 20 mumol/L of Rg5 for 24 h, Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex production and increasing the P21CIPI. rg5 37-40 cyclin dependent kinase 2 Homo sapiens 117-151 31883767-5 2020 As for cell growth, Icariside II arrested cell cycle at G0/G1 phase through AKT/Cyclin E/CDK 2 from transcriptional and translational levels. baohuoside I 20-32 cyclin dependent kinase 2 Homo sapiens 89-94 32476373-6 2020 After the treatment of 20 mumol/L of Rg5 for 24 h, Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex production and increasing the P21CIPI. rg5 51-54 cyclin dependent kinase 2 Homo sapiens 117-151 32476373-6 2020 After the treatment of 20 mumol/L of Rg5 for 24 h, Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex production and increasing the P21CIPI. rg5 51-54 cyclin dependent kinase 2 Homo sapiens 153-157 31936152-6 2020 CDK2 was downregulated by OTA exposure, and its overexpression partially blocked the OTA-induced G1 but not G2 cell-cycle arrest. ochratoxin A 26-29 cyclin dependent kinase 2 Homo sapiens 0-4 32123579-4 2020 We demonstrate here that cyclin-dependent kinase (CDK) 2 interacts with NF90 and phosphorylated it at serine382. serine382 102-111 cyclin dependent kinase 2 Homo sapiens 25-56 31809756-9 2020 Treatment with sesamin caused cell cycle arrest at G1 phase and inhibited cyclin D1 and CDK2 expression. sesamin 15-22 cyclin dependent kinase 2 Homo sapiens 88-92 31936152-7 2020 We, therefore, propose CDK2 as one of the key regulators of the G1 cell-cycle arrest induced by low nanomolar concentrations of OTA. ochratoxin A 128-131 cyclin dependent kinase 2 Homo sapiens 23-27 31936152-6 2020 CDK2 was downregulated by OTA exposure, and its overexpression partially blocked the OTA-induced G1 but not G2 cell-cycle arrest. ochratoxin A 85-88 cyclin dependent kinase 2 Homo sapiens 0-4 31822694-6 2019 Here we show that not only Cdk2 but Cdk1 phosphorylates p27 at the Thr-187. Threonine 67-70 cyclin dependent kinase 2 Homo sapiens 27-31 31696811-10 2020 Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding. Chalcone 30-38 cyclin dependent kinase 2 Homo sapiens 55-59 31696811-10 2020 Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding. Chalcone 128-136 cyclin dependent kinase 2 Homo sapiens 55-59 31696811-10 2020 Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding. Colchicine 154-164 cyclin dependent kinase 2 Homo sapiens 55-59 31696811-10 2020 Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding. Ustiloxin 165-174 cyclin dependent kinase 2 Homo sapiens 55-59 31241436-6 2020 METHODS: CDK1 and CDK2 have 89.19% similar residues and 74.32% identical residues, their structures especially the ATP-binding sites are of great similarity. Adenosine Triphosphate 115-118 cyclin dependent kinase 2 Homo sapiens 18-22 33132266-3 2020 Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3. Dictyodendrin 5-18 cyclin dependent kinase 2 Homo sapiens 68-72 31847444-9 2019 We found that binding of 6-N,6-N-dimethyl-9-(2-phenylethyl)purine-2,6-diamine stabilizes the structure of CDK2 and causes minimal conformational change. 6-n,6-n-dimethyl-9-(2-phenylethyl)purine-2,6-diamine 25-77 cyclin dependent kinase 2 Homo sapiens 106-110 31250757-0 2020 A definitive pharmacophore modelling study on CDK2 ATP pocket binders: tracing the path of new virtual high-throughput screenings. Adenosine Triphosphate 51-54 cyclin dependent kinase 2 Homo sapiens 46-50 31250757-5 2020 In this work, one-hundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket were submitted to short MD simulations (10ns) and free energy calculation. Adenosine Triphosphate 83-86 cyclin dependent kinase 2 Homo sapiens 78-82 31814282-6 2020 We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria-dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Mifepristone 14-26 cyclin dependent kinase 2 Homo sapiens 80-84 31740384-5 2020 We have determined that both the CDK2 depletion and pharmacological inhibitor of CDK2 significantly sensitize three subtypes of AML cells (including two non-APL cells) to ATRA-induced cell differentiation. Tretinoin 171-175 cyclin dependent kinase 2 Homo sapiens 33-37 31740384-5 2020 We have determined that both the CDK2 depletion and pharmacological inhibitor of CDK2 significantly sensitize three subtypes of AML cells (including two non-APL cells) to ATRA-induced cell differentiation. Tretinoin 171-175 cyclin dependent kinase 2 Homo sapiens 81-85 31740384-8 2020 Thus, our work not only provides relevant experimental evidence for further validating CDK2 as a target for differentiation therapy, but also uncovers the future clinical application of CDK2 inhibitors in ATRA-based differentiation therapeutics for AML. Tretinoin 205-209 cyclin dependent kinase 2 Homo sapiens 87-91 31740384-8 2020 Thus, our work not only provides relevant experimental evidence for further validating CDK2 as a target for differentiation therapy, but also uncovers the future clinical application of CDK2 inhibitors in ATRA-based differentiation therapeutics for AML. Tretinoin 205-209 cyclin dependent kinase 2 Homo sapiens 186-190 31513938-0 2019 Design, synthesis and molecular docking of novel pyrazolo[1,5-a][1,3,5]triazine derivatives as CDK2 inhibitors. pyrazolo(1,5-a)(1,3,5)triazine 49-79 cyclin dependent kinase 2 Homo sapiens 95-99 31439587-6 2019 Importantly, olaparib (OLA) or talazoparib (TALA) suppressed these activities, and the combination of OLA and dinaciclib (DINA), an inhibitor of CDK2 and CDK5, which also inhibits Rb1 phosphorylation, suppressed NED, and significantly improved therapeutic efficiency in neuroendocrine prostate cancer (NEPC) cells in vitro and in NEPC tumors in vivo. dinaciclib 110-120 cyclin dependent kinase 2 Homo sapiens 145-149 31513938-2 2019 In this respect, a series of novel pyrazolo[1,5-a][1,3,5]triazine derivatives were designed, synthesized and evaluated for CDK2 enzyme inhibitory and anticancer activity. pyrazolo(1,5-a)(1,3,5)triazine 35-65 cyclin dependent kinase 2 Homo sapiens 123-127 31513938-5 2019 Molecular docking revealed the binding mode of these new compounds into the roscovitine binding site of CDK2 enzyme (PDB code: 3ddq). Roscovitine 76-87 cyclin dependent kinase 2 Homo sapiens 104-108 31431461-8 2019 At the beginning of S phase, Cdk2 phosphorylated c-Myc at Serine 62, promoting its association with the miR-571 promoter region. Serine 58-64 cyclin dependent kinase 2 Homo sapiens 29-33 31588915-5 2019 However, isorhamnetin increased expression of p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, and increased p21 complexed with Cdk2 and Cdc2. 3-methylquercetin 9-21 cyclin dependent kinase 2 Homo sapiens 136-140 31635244-9 2019 beta- Caryophyllene induced G1 cell cycle arrest by downregulating cyclin D1, cyclin E, cyclin-dependent protein kinase (CDK) -2, -4, and -6, and RB phosphorylation, and by upregulating p21CIP1/WAF1 and p27KIP1. caryophyllene 6-19 cyclin dependent kinase 2 Homo sapiens 88-140 31603865-12 2019 Further, upregulation of LIPCAR increased CDK2, p21, PCNA, MMP2, MMP9, VEGF-A, Ang-2, and TF expression and decreased p21 expression. lipcar 25-31 cyclin dependent kinase 2 Homo sapiens 42-46 31451657-4 2019 Intriguingly, in terminally differentiated neutrophils, miR-199 alters the cell cycle-related pathways and directly suppresses cyclin-dependent kinase 2 (Cdk2), whose known activity is restricted to cell cycle progression and cell differentiation. mir-199 56-63 cyclin dependent kinase 2 Homo sapiens 154-158 31254921-1 2019 To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. pyrimidine-based benzothiazole 73-103 cyclin dependent kinase 2 Homo sapiens 17-21 31254921-6 2019 These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents. pyrimidine-benzothiazole 32-56 cyclin dependent kinase 2 Homo sapiens 90-94 31467029-2 2019 Here, we report the discovery of an aminopyrazole, 2-([1,1"-biphenyl]-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide (analog 24), which selectively inhibited cyclin-dependent kinase (CDK) 5 over CDK2 in cancer cell lines. 3-aminopyrazole 36-49 cyclin dependent kinase 2 Homo sapiens 196-200 31467029-2 2019 Here, we report the discovery of an aminopyrazole, 2-([1,1"-biphenyl]-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide (analog 24), which selectively inhibited cyclin-dependent kinase (CDK) 5 over CDK2 in cancer cell lines. 2-([1,1"-biphenyl]-4-yl)-n-(5-cyclobutyl-1h-pyrazol-3-yl)acetamide 51-117 cyclin dependent kinase 2 Homo sapiens 196-200 31524277-10 2019 Exposure to PFOA also induced the expression of vimentin, SGK1, cyclin E2, CDK2, AKT, PI3K and Bcl-2, but suppressed the expression of Bax in the RD cells. perfluorooctanoic acid 12-16 cyclin dependent kinase 2 Homo sapiens 75-79 31619992-6 2019 Further investigation revealed that the key proteins (including cyclinD1, cyclinE1, cyclinB1, CDK2, and CDK4) were involved in the cell regulation by NAT-F. neoantimycin 150-155 cyclin dependent kinase 2 Homo sapiens 94-98 31572198-4 2019 In vitro studies showed that TFP induced G0/G1 cell cycle arrest to dramatically inhibit CRC cell proliferation through downregulating cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, and cyclin E and upregulating p27. Trifluoperazine 29-32 cyclin dependent kinase 2 Homo sapiens 135-166 31350280-4 2019 Our data indicate that CDK2-mediated phosphorylation of NRF1 can occur at two distinct serine residues and negatively regulates NRF1 DNA binding activity in vitro. Serine 87-93 cyclin dependent kinase 2 Homo sapiens 23-27 31462218-7 2019 In this study, to elucidate the effect of CDKs inhibition in hESCs we used Roscovitine (ROSC), a purine analogue that selectively inhibits the activities of these kinases. Roscovitine 75-86 cyclin dependent kinase 2 Homo sapiens 42-46 31155753-7 2019 In conclusion, our results indicate that resveratrol acts as a potential inducer to enhance the chemosensitivity of breast cancer and also suggest that miR-122-5p is involved in the pathway of cell-cycle arrest by targeting Bcl-2 and CDKs. Resveratrol 41-52 cyclin dependent kinase 2 Homo sapiens 234-238 31462218-7 2019 In this study, to elucidate the effect of CDKs inhibition in hESCs we used Roscovitine (ROSC), a purine analogue that selectively inhibits the activities of these kinases. Roscovitine 88-92 cyclin dependent kinase 2 Homo sapiens 42-46 31387245-4 2019 Our data showed that LCA inhibited the expression of cyclin A, cyclin B1, and Wee1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdc2 and Cdk2. licochalcone A 21-24 cyclin dependent kinase 2 Homo sapiens 210-214 31438633-3 2019 Genistein down-regulated the levels of cyclin A and cyclin B1, but up-regulated the levels of p21WAF1/CIP1, cyclin-dependent kinase (Cdk) inhibitor, that was complexed with Cdc2 and Cdk2. Genistein 0-9 cyclin dependent kinase 2 Homo sapiens 182-186 31272794-0 2019 Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2. 9h-purin 19-27 cyclin dependent kinase 2 Homo sapiens 72-76 31272794-2 2019 In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one molecule to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. purine 139-144 cyclin dependent kinase 2 Homo sapiens 68-72 31455378-6 2019 Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines. Metformin 108-117 cyclin dependent kinase 2 Homo sapiens 92-100 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Tretinoin 164-166 cyclin dependent kinase 2 Homo sapiens 98-123 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Tretinoin 164-166 cyclin dependent kinase 2 Homo sapiens 125-129 31077767-7 2019 Midostaurin induced G2/M arrest and inhibited CDK2, preventing the phosphorylation of SAMHD1 associated to inhibition of its dNTPase activity. midostaurin 0-11 cyclin dependent kinase 2 Homo sapiens 46-50 31257544-11 2019 Cell cycle arrest in the G0/G1 phase was induced by siGCF2, which was accompanied by changes in the levels of cyclin E, CDK2 and p21. sigcf2 52-58 cyclin dependent kinase 2 Homo sapiens 120-124 30911957-6 2019 Berberine decreased the expression of protein levels of cyclin D1, cyclin E, CDK2, CDK4, and CDK6 to cause G1 phase arrest. Berberine 0-9 cyclin dependent kinase 2 Homo sapiens 77-81 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. U 0126 211-216 cyclin dependent kinase 2 Homo sapiens 98-123 30859584-4 2019 Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin-dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. U 0126 211-216 cyclin dependent kinase 2 Homo sapiens 125-129 31045274-9 2019 Finally, our in vivo xenograft data showed that the combination of flavopiridol, a cyclin E1/CDK2 inhibitor, overcomes the TMZ resistant by inducing higher apoptosis. alvocidib 67-79 cyclin dependent kinase 2 Homo sapiens 93-97 31045274-9 2019 Finally, our in vivo xenograft data showed that the combination of flavopiridol, a cyclin E1/CDK2 inhibitor, overcomes the TMZ resistant by inducing higher apoptosis. Temozolomide 123-126 cyclin dependent kinase 2 Homo sapiens 93-97 31059711-3 2019 Coimmunoprecipitation studies demonstrated that TPL causes S phase cell cycle arrest by suppressing the formation of cyclin A-phosphor (p)-cyclin-dependent kinas 2 (CDK2) (Thr 39) complexes. Threonine 172-175 cyclin dependent kinase 2 Homo sapiens 165-169 31358785-5 2019 Ormeloxifene efficiently attenuated tumorigenic and metastatic properties of cervical cancer cells via arresting cell cycle at G1-S transition, inducing apoptosis, decreasing PI3K and Akt phosphorylation, mitochondrial membrane potential, and modulating G1-S transition related proteins (p21, cyclin E and Cdk2). ormeloxifene 0-12 cyclin dependent kinase 2 Homo sapiens 306-310 31406477-7 2019 Moreover, the expression levels of Bcl-2, survivin, CDK2 and MMP-2 significantly decreased in SCLC cells treated with paclitaxel targeting nanobubbles, whereas the expression of caspase-3 and Rb were increased. Paclitaxel 118-128 cyclin dependent kinase 2 Homo sapiens 52-56 31059711-4 2019 Ectopic expression of constitutively active protein kinase B1 (Akt1) blocks the induction of S phase arrest and the suppression of cyclin A expression and CDK2 Thr 39 phosphorylation by TPL. Threonine 160-163 cyclin dependent kinase 2 Homo sapiens 155-159 31059711-5 2019 Expression of the phosphomimetic mutant CDK2 (T39E) rescues the cells from TPL-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TPL-triggered S phase arrest. triptolide 75-78 cyclin dependent kinase 2 Homo sapiens 40-44 30971469-8 2019 Our findings reveal a role for CDK2 in differential modulation of HIV-1 gene expression in myeloid cells and in T cells and provide a novel strategy to reactivate monocytic reservoirs with BETi during cART.IMPORTANCE Bromodomain inhibitors have been reported to activate HIV-1 transcription in vitro, but their effect on activation of HIV-1 reservoirs during cART in vivo is unclear. beti 189-193 cyclin dependent kinase 2 Homo sapiens 31-35 31078043-4 2019 In addition, we found that overexpression of miR-128-3p arrested breast cancer cells in G0/G1 phase by affecting expression of CDK4/CDK6/Cyclin D1 and CDK2/Cyclin E1. mir-128-3p 45-55 cyclin dependent kinase 2 Homo sapiens 151-155 31354907-6 2019 The results showed that DpdtbA exhibited an excellent antiproliferative effect for ESC cell lines (IC50 <= 4.5 +- 0.4 muM for Kyse 450, 3.2 +- 0.6 muM for Kyse 510 cell, and 10.0 +- 0.6 muM for Kyse 150) and led to cell cycle arrest at the S phase which correlated to CDK2 downregulation. dpdtba 24-30 cyclin dependent kinase 2 Homo sapiens 271-275 31261874-5 2019 Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Telmisartan 0-11 cyclin dependent kinase 2 Homo sapiens 150-175 31164422-2 2019 Here, we reveal that cyclin-dependent kinase A;1 (CDKA;1), the homolog of human Cdk1 and Cdk2, is a major regulator of meiotic recombination in Arabidopsis Arabidopsis plants with reduced CDKA;1 activity experienced a decrease of class I COs, especially lowering recombination rates in centromere-proximal regions. carbonyl sulfide 238-241 cyclin dependent kinase 2 Homo sapiens 89-93 31184118-4 2019 The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. ros 4-7 cyclin dependent kinase 2 Homo sapiens 166-170 31184118-4 2019 The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. juglone 57-64 cyclin dependent kinase 2 Homo sapiens 166-170 31216756-6 2019 The concept is illustrated by a docking study into the ATP-binding site of CDK2, using the S4MPLE program to generate thousands of poses for each ligand. Adenosine Triphosphate 55-58 cyclin dependent kinase 2 Homo sapiens 75-79 31239643-12 2019 Furthermore, notopterol induced the G0/G1 cell-cycle arrest as determined using flow cytometry, which may be related to the regulation of cell-cycle-related proteins p53, CDK2, CDK4, Cyclin D1, Cyclin E, and survivin. notopterol 13-23 cyclin dependent kinase 2 Homo sapiens 171-175 30971469-11 2019 Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in HIV-1-infected CD4 T cells, via CDK2-dependent mechanisms. GSK1210151A 13-21 cyclin dependent kinase 2 Homo sapiens 129-133 31073278-15 2019 Consistently, protein expression of p57, CDK2, cyclin E2, and pRb was significantly impacted by apatinib in PC9GR cells. apatinib 96-104 cyclin dependent kinase 2 Homo sapiens 41-45 30947332-6 2019 The in vitro studies revealed that DCZ0801 could inhibit cell proliferation and induce apoptosis by regulating both caspase-dependent and mitogen-activated protein kinase signaling pathways, inducing S-phase arrest of the cell cycle related to downregulation of CDK2, cyclin-A2, and CDC25A protein expression. dcz0801 35-42 cyclin dependent kinase 2 Homo sapiens 262-266 31218209-8 2019 In addition, we found that pristimerin decreased the protein expression of CDK2, CDK4, cyclin E, and BCL-2 and increased the expression of CDKN1B. pristimerin 27-38 cyclin dependent kinase 2 Homo sapiens 75-79 30772267-0 2019 Palbociclib triggers apoptosis in bladder cancer cells by Cdk2-induced Rad9-mediated reorganization of the Bak.Bcl-xl complex. palbociclib 0-11 cyclin dependent kinase 2 Homo sapiens 58-62 30772267-6 2019 Cdk2 activation was important to palbociclib-induced apoptotic triggering activity, since depletion of Cdk2 significantly inhibited caspase-3 activation and cell apoptosis. palbociclib 33-44 cyclin dependent kinase 2 Homo sapiens 0-4 30772267-6 2019 Cdk2 activation was important to palbociclib-induced apoptotic triggering activity, since depletion of Cdk2 significantly inhibited caspase-3 activation and cell apoptosis. palbociclib 33-44 cyclin dependent kinase 2 Homo sapiens 103-107 30685646-9 2019 Molecular docking study for the most potent cytotoxic compounds (7c and 8a-c) rationalized their superior CDK2 inhibitory activity through their hydrogen bonding and hydrophobic interactions with the key amino acids in the CDK2 binding site. Hydrogen 145-153 cyclin dependent kinase 2 Homo sapiens 106-110 30976006-2 2019 Cell division progresses when stably Cdk2/cyclin A-bound p27 is phosphorylated on one or two structurally occluded tyrosine residues and a distal threonine residue (T187), triggering degradation of p27. Threonine 146-155 cyclin dependent kinase 2 Homo sapiens 37-41 30976006-2 2019 Cell division progresses when stably Cdk2/cyclin A-bound p27 is phosphorylated on one or two structurally occluded tyrosine residues and a distal threonine residue (T187), triggering degradation of p27. Tyrosine 115-123 cyclin dependent kinase 2 Homo sapiens 37-41 30682722-0 2019 Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity. pyrazole 80-88 cyclin dependent kinase 2 Homo sapiens 55-59 30682722-0 2019 Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity. pyrazolo(1,5-a)pyrimidine 93-119 cyclin dependent kinase 2 Homo sapiens 55-59 30682722-1 2019 Different series of novel pyrazole and pyrazolo[1,5-a] pyrimidine derivatives (2a-g), (3a-c), (7a-d) and (10a-e) were designed, synthesized and evaluated for their ability to inhibit CDK2/cyclin A2 enzyme in vitro. pyrazole 26-34 cyclin dependent kinase 2 Homo sapiens 183-187 30682722-1 2019 Different series of novel pyrazole and pyrazolo[1,5-a] pyrimidine derivatives (2a-g), (3a-c), (7a-d) and (10a-e) were designed, synthesized and evaluated for their ability to inhibit CDK2/cyclin A2 enzyme in vitro. pyrazolo(1,5-a)pyrimidine 39-65 cyclin dependent kinase 2 Homo sapiens 183-187 30685646-0 2019 New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies. thiazol-hydrazono-coumarin 4-30 cyclin dependent kinase 2 Homo sapiens 89-93 31018506-11 2019 Activation of the key regulators p53 and p21 inhibited the cyclin-dependent kinases Cdk2 and Cdk4, suggesting that p53 and p21 activation in GO-PtNP-treated cells caused genotoxic stress and apoptosis. (4-toluoyl-3-nitro)piperazine 144-148 cyclin dependent kinase 2 Homo sapiens 84-88 32259055-6 2019 S phase arrest was induced with the topoisomerase I inhibitor SN38; the addition of CHK1i rapidly activated CDK2, inducing S phase progression that was inhibited by the CDK2 inhibitor CVT-313. Irinotecan 62-66 cyclin dependent kinase 2 Homo sapiens 169-173 32259055-6 2019 S phase arrest was induced with the topoisomerase I inhibitor SN38; the addition of CHK1i rapidly activated CDK2, inducing S phase progression that was inhibited by the CDK2 inhibitor CVT-313. CVT 313 184-191 cyclin dependent kinase 2 Homo sapiens 108-112 32259055-6 2019 S phase arrest was induced with the topoisomerase I inhibitor SN38; the addition of CHK1i rapidly activated CDK2, inducing S phase progression that was inhibited by the CDK2 inhibitor CVT-313. CVT 313 184-191 cyclin dependent kinase 2 Homo sapiens 169-173 30712329-9 2019 Using ChIP assay, we demonstrated that Nanog could directly bind to promoters of Cdk2, Cdk6, FGF4, c-Myc and alpha-Mangostin inhibited Nanog binding to these promoters. mangostin 109-124 cyclin dependent kinase 2 Homo sapiens 81-85 30700607-7 2019 Moreover, we demonstrated that cyclin A- and E-associated CDK2 complexes phosphorylated BDLF4 in vitro, and we identified several serine/threonine phosphorylation sites in BDLF4. Serine 130-136 cyclin dependent kinase 2 Homo sapiens 58-62 30700607-7 2019 Moreover, we demonstrated that cyclin A- and E-associated CDK2 complexes phosphorylated BDLF4 in vitro, and we identified several serine/threonine phosphorylation sites in BDLF4. Threonine 137-146 cyclin dependent kinase 2 Homo sapiens 58-62 30589568-3 2019 NF-YA harbors 2 serines-Ser320 and Ser326-shown to be phosphorylated by cyclin-dependent kinase 2. Serine 16-23 cyclin dependent kinase 2 Homo sapiens 72-97 30879017-7 2019 RESULTS Murrayanine treatment resulted in significant dose-dependent inhibition of the growth of A549 cells (p<0.05), with an IC50 of 9 microM, and arrested the cells at the G2/M phase of the cell cycle, reduced the expression of cyclin D and E, CDK2, 4, and 6, and increased the expression of p21 and p27. murrayanine 8-19 cyclin dependent kinase 2 Homo sapiens 249-253 30902084-8 2019 TSA reduced PCNA, cyclin D1, cyclin E1, CDK2, p16 and p21 expressions and stimulated CDK6 levels. trichostatin A 0-3 cyclin dependent kinase 2 Homo sapiens 40-44 30824767-6 2019 Fenofibrate caused S and G2/M cell cycle arrest by inducing cyclin A/Cdk2 and reducing cyclin D1 and E protein levels in Hep3B cells. Fenofibrate 0-11 cyclin dependent kinase 2 Homo sapiens 69-73 30229997-5 2019 Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. oridonin 40-48 cyclin dependent kinase 2 Homo sapiens 168-172 30825242-9 2019 Furthermore, pristimerin resulted in the G0/G1 cell-cycle arrest, reducing the expression of cell cycle-related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy-related proteins (LC3) in QBC cell line. pristimerin 13-24 cyclin dependent kinase 2 Homo sapiens 132-136 31384770-9 2019 The QPLD analysis of docking studies revealed that PAC exhibited better binding affinity of - 5.23, - 5.17 and - 4.43, - 4.47 kcal/mol against BCL-XL, CDK2 and were compared with 5-FU respectively, which significantly reveals the anticancerous activity of Proanthocyanidin compound. proanthocyanidin 51-54 cyclin dependent kinase 2 Homo sapiens 151-155 30949393-4 2019 Flow cytometry analysis revealed that hydrangenol suppressed the VEGF-induced inhibition of G1-cell cycle phase and also decreased cyclin D1, cyclin E, CDK2, and CDK4 levels. hydrangenol 38-49 cyclin dependent kinase 2 Homo sapiens 152-156 30573684-0 2019 Inhibition of checkpoint kinase 1 following gemcitabine-mediated S phase arrest results in CDC7- and CDK2-dependent replication catastrophe. gemcitabine 44-55 cyclin dependent kinase 2 Homo sapiens 101-105 31984903-3 2019 The new fluorinated modified rhodanines 2-16 were evaluated as enzymatic probes for cellobiase activity produced by fungi and as CDK2 inhibitors of tumor cells. Rhodanine 29-39 cyclin dependent kinase 2 Homo sapiens 129-133 30729133-7 2019 Prolonged exposure to high glucose and insulin enhanced cyclin D, cyclin-dependent kinase 4 (Cdk4), and Cdk2 expression and suppressed cyclin-dependent kinase inhibitors p21 and p15/16 in HBlEpC cotreated with pioglitazone and metformin. Glucose 27-34 cyclin dependent kinase 2 Homo sapiens 104-108 30182857-11 2019 CONCLUSION: Our study suggests that cordycepin is effective against cervical cancer cells, and regulating cell cycle via cell cycle proteins, especially downregulating Cdk-2, and inducing apoptosis by generating ROS are among the mechanisms of anticancer activities of cordycepin. cordycepin 36-46 cyclin dependent kinase 2 Homo sapiens 168-173 30472117-4 2019 We have used biophysical measurements and X-ray crystallography to investigate the ATP-competitive inhibitor binding properties of cyclin-free and cyclin-bound CDK1 and CDK2. Adenosine Triphosphate 83-86 cyclin dependent kinase 2 Homo sapiens 169-173 30389635-5 2019 Celastrol resulted in a G2/M cell cycle arrest, accompanied with the down-regulation of Cyclin D1, CDK2, and CDK4. celastrol 0-9 cyclin dependent kinase 2 Homo sapiens 99-103 31038080-0 2019 Novel Pyrazolo[3,4-d]pyrimidines as Potential Cytotoxic Agents: Design, Synthesis, Molecular Docking and CDK2 Inhibition. pyrazolo(3,4-d)pyrimidine 6-32 cyclin dependent kinase 2 Homo sapiens 105-109 31038080-1 2019 BACKGROUND: Pyrazolo[3,4-d]pyrimidine scaffold was reported to possess potent cytotoxic and CDK2 inhibitory activity as analogue of roscovitine. pyrazolo(3,4-d)pyrimidine 12-37 cyclin dependent kinase 2 Homo sapiens 92-96 31038080-1 2019 BACKGROUND: Pyrazolo[3,4-d]pyrimidine scaffold was reported to possess potent cytotoxic and CDK2 inhibitory activity as analogue of roscovitine. Roscovitine 132-143 cyclin dependent kinase 2 Homo sapiens 92-96 31038080-2 2019 OBJECTIVE: To design and synthesize novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine derivatives as bioisosters of roscovitine with potential cytotoxic and CDK2 inhibitory activity. 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine 42-85 cyclin dependent kinase 2 Homo sapiens 157-161 31038080-2 2019 OBJECTIVE: To design and synthesize novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine derivatives as bioisosters of roscovitine with potential cytotoxic and CDK2 inhibitory activity. Roscovitine 116-127 cyclin dependent kinase 2 Homo sapiens 157-161 31038080-14 2019 The Molecular docking results revealed that compound 4 interacted with the same key amino acids as roscovitine in the active site of CDK2 enzyme with a marked docking score (-14.1031 kcal/mol). Roscovitine 99-110 cyclin dependent kinase 2 Homo sapiens 133-137 31984903-4 2019 MATERIALS AND METHODS: Novel fluorine substituted N-alkyl, S-alkyl and amino-rhodanines were obtained via Hydroxy methylation, Mannich reactions, chlorination and amination of 5-(4"-fluorophenylene)-2-thioxothiazolidin- 4-one, and the enzymatic effects of cellobiase produced by fungi and /or CDK2 inhibition of tumor cells were evaluated. Fluorine 29-37 cyclin dependent kinase 2 Homo sapiens 293-297 31984903-4 2019 MATERIALS AND METHODS: Novel fluorine substituted N-alkyl, S-alkyl and amino-rhodanines were obtained via Hydroxy methylation, Mannich reactions, chlorination and amination of 5-(4"-fluorophenylene)-2-thioxothiazolidin- 4-one, and the enzymatic effects of cellobiase produced by fungi and /or CDK2 inhibition of tumor cells were evaluated. Alkanesulfonates 50-57 cyclin dependent kinase 2 Homo sapiens 293-297 31984903-4 2019 MATERIALS AND METHODS: Novel fluorine substituted N-alkyl, S-alkyl and amino-rhodanines were obtained via Hydroxy methylation, Mannich reactions, chlorination and amination of 5-(4"-fluorophenylene)-2-thioxothiazolidin- 4-one, and the enzymatic effects of cellobiase produced by fungi and /or CDK2 inhibition of tumor cells were evaluated. Alkanesulfonates 59-66 cyclin dependent kinase 2 Homo sapiens 293-297 31984903-4 2019 MATERIALS AND METHODS: Novel fluorine substituted N-alkyl, S-alkyl and amino-rhodanines were obtained via Hydroxy methylation, Mannich reactions, chlorination and amination of 5-(4"-fluorophenylene)-2-thioxothiazolidin- 4-one, and the enzymatic effects of cellobiase produced by fungi and /or CDK2 inhibition of tumor cells were evaluated. Rhodanine 71-87 cyclin dependent kinase 2 Homo sapiens 293-297 31984903-8 2019 CONCLUSION: Various N, S and O-alkyl derivatives of fluorine-substituted rhodanines were prepared via a simple method and used as enzymatic probes for cellobiase activity produced by fungi and CDK2 inhibitors for tumor cells. Nitrogen 2-3 cyclin dependent kinase 2 Homo sapiens 193-197 31984903-8 2019 CONCLUSION: Various N, S and O-alkyl derivatives of fluorine-substituted rhodanines were prepared via a simple method and used as enzymatic probes for cellobiase activity produced by fungi and CDK2 inhibitors for tumor cells. Alkanesulfonates 29-36 cyclin dependent kinase 2 Homo sapiens 193-197 31984903-8 2019 CONCLUSION: Various N, S and O-alkyl derivatives of fluorine-substituted rhodanines were prepared via a simple method and used as enzymatic probes for cellobiase activity produced by fungi and CDK2 inhibitors for tumor cells. Fluorine 52-60 cyclin dependent kinase 2 Homo sapiens 193-197 31984903-8 2019 CONCLUSION: Various N, S and O-alkyl derivatives of fluorine-substituted rhodanines were prepared via a simple method and used as enzymatic probes for cellobiase activity produced by fungi and CDK2 inhibitors for tumor cells. Rhodanine 73-83 cyclin dependent kinase 2 Homo sapiens 193-197 31452106-8 2019 To illustrate the process, we describe the molecular docking of the competitive inhibitor roscovitine against the structure of human cyclin-dependent kinase 2. Roscovitine 90-101 cyclin dependent kinase 2 Homo sapiens 133-158 30384040-9 2019 Mechanistic studies revealed that ClQ-Pt and BrQ-Pt caused T-24 cell cycle arrest at the S phase, as shown by the down-regulation of cyclin A and CDK2 expression levels. clq-pt 34-40 cyclin dependent kinase 2 Homo sapiens 146-150 30384040-9 2019 Mechanistic studies revealed that ClQ-Pt and BrQ-Pt caused T-24 cell cycle arrest at the S phase, as shown by the down-regulation of cyclin A and CDK2 expression levels. brq-pt 45-51 cyclin dependent kinase 2 Homo sapiens 146-150 28374118-1 2018 In the proposed work, we have explicated the mechanism of dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) modulated cell proliferation by assessing the plausible binding with CASPASES, BAX, Bcl-2, MDM2, p53, p21, p16, CylinD1-CDK4 complex, CylinE1-CDK2 complex, H-Ras, K-Ras, BRCA1, and BRCA2 through exploiting the inherent potential of AutoDock Tools 4.0. Benzo(a)pyrene 87-101 cyclin dependent kinase 2 Homo sapiens 249-253 30599108-0 2019 Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening. thiazole-tetrazole 49-67 cyclin dependent kinase 2 Homo sapiens 108-113 30599108-0 2019 Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening. Triazoles 71-79 cyclin dependent kinase 2 Homo sapiens 108-113 30599108-0 2019 Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening. Glycosides 87-97 cyclin dependent kinase 2 Homo sapiens 108-113 30218747-0 2018 Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2 mediated signaling pathway in human non-small cell lung carcinoma A549 cells. pyrazole 23-34 cyclin dependent kinase 2 Homo sapiens 73-78 30218747-4 2018 In the present study the anti-cancer mechanism of pyrazole, was examined by the expression level of proteins Epidermal growth factor receptor (EGFR), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cyclin-dependent kinase-2 (CDK-2) which are commonly associated with the cell signaling pathways that control cell survival and apoptosis, that could facilitate to develop a novel target and effective treatment approach for patients with NSCLC. pyrazole 50-58 cyclin dependent kinase 2 Homo sapiens 214-239 30218747-4 2018 In the present study the anti-cancer mechanism of pyrazole, was examined by the expression level of proteins Epidermal growth factor receptor (EGFR), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cyclin-dependent kinase-2 (CDK-2) which are commonly associated with the cell signaling pathways that control cell survival and apoptosis, that could facilitate to develop a novel target and effective treatment approach for patients with NSCLC. pyrazole 50-58 cyclin dependent kinase 2 Homo sapiens 241-246 30218747-7 2018 Furthermore, Pyrazole suppresses the expression of CDK-2 resulting in cell cycle arrest at G1 phase and in the G1-S phase transition. pyrazole 13-21 cyclin dependent kinase 2 Homo sapiens 51-56 30181387-8 2018 Such drug-mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy.Conclusions: Cyclin E is a potential biomarker of response (i) for AZD1775 as monotherapy in cyclin E-high TNBC tumors and (ii) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E-low TNBC tumors. adavosertib 208-215 cyclin dependent kinase 2 Homo sapiens 309-313 30181387-8 2018 Such drug-mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy.Conclusions: Cyclin E is a potential biomarker of response (i) for AZD1775 as monotherapy in cyclin E-high TNBC tumors and (ii) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E-low TNBC tumors. adavosertib 208-215 cyclin dependent kinase 2 Homo sapiens 309-313 30864522-0 2019 Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides. pyrimidine 87-97 cyclin dependent kinase 2 Homo sapiens 32-37 30864522-0 2019 Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides. Glycosides 125-135 cyclin dependent kinase 2 Homo sapiens 32-37 30508677-6 2019 Subsequently, CDK2-cyclin E catalyzes the hyperphosphorylation of Rb that promotes the release and activation of the E2F transcription factor, which in turn lead to the biosynthesis of dozens of proteins required for cell cycle progression. Rubidium 66-68 cyclin dependent kinase 2 Homo sapiens 14-18 30515903-5 2018 The authors validated our workflow using CDK2 kinase, which has an especially-closed ATP-binding pocket in the apo-form, and several inhibitors. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 41-45 28374118-1 2018 In the proposed work, we have explicated the mechanism of dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) modulated cell proliferation by assessing the plausible binding with CASPASES, BAX, Bcl-2, MDM2, p53, p21, p16, CylinD1-CDK4 complex, CylinE1-CDK2 complex, H-Ras, K-Ras, BRCA1, and BRCA2 through exploiting the inherent potential of AutoDock Tools 4.0. dibenzo(a,l)pyrene 58-76 cyclin dependent kinase 2 Homo sapiens 249-253 28374118-1 2018 In the proposed work, we have explicated the mechanism of dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) modulated cell proliferation by assessing the plausible binding with CASPASES, BAX, Bcl-2, MDM2, p53, p21, p16, CylinD1-CDK4 complex, CylinE1-CDK2 complex, H-Ras, K-Ras, BRCA1, and BRCA2 through exploiting the inherent potential of AutoDock Tools 4.0. Benzo(a)pyrene 79-81 cyclin dependent kinase 2 Homo sapiens 249-253 30197029-0 2018 Synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as potent CDK2 inhibitors. 5,6-dihydropyrimido[4,5-f]quinazoline 45-82 cyclin dependent kinase 2 Homo sapiens 105-109 30247801-4 2018 Mechanism analysis found that tigecycline led to cell cycle arrest at G0/G1 with down-regulation of p21, CDK2 and cyclin D1, rather than induced apoptosis, in MM cells. Tigecycline 30-41 cyclin dependent kinase 2 Homo sapiens 105-109 30145203-0 2018 Integrated proteomic and phosphoproteomic analyses of cisplatin-sensitive and resistant bladder cancer cells reveal CDK2 network as a key therapeutic target. Cisplatin 54-63 cyclin dependent kinase 2 Homo sapiens 116-120 30145203-9 2018 Additional network analysis of significantly altered proteins revealed CDK2, CHEK1, and ERBB2 as central regulators mediating cisplatin resistance. Cisplatin 126-135 cyclin dependent kinase 2 Homo sapiens 71-75 30145203-10 2018 In addition to this, we identified the CDK2 network, which consists of CDK2 and its 5 substrates, as being significantly associated with poor survival after cisplatin chemotherapy. Cisplatin 157-166 cyclin dependent kinase 2 Homo sapiens 39-43 30145203-10 2018 In addition to this, we identified the CDK2 network, which consists of CDK2 and its 5 substrates, as being significantly associated with poor survival after cisplatin chemotherapy. Cisplatin 157-166 cyclin dependent kinase 2 Homo sapiens 71-75 30423939-0 2018 Molecular Modeling and Design Studies of Purine Derivatives as Novel CDK2 Inhibitors. purine 41-47 cyclin dependent kinase 2 Homo sapiens 69-73 30423939-2 2018 Purine heterocycles have attracted particular attention as the scaffolds for the development of CDK2 inhibitors. purine 0-6 cyclin dependent kinase 2 Homo sapiens 96-100 30423939-3 2018 To explore the interaction mechanism and the structure-activity relationship (SAR) and to design novel candidate compounds as potential CDK2 inhibitors, a systematic molecular modeling study was conducted on 35 purine derivatives as CDK2 inhibitors by combining three-dimensional quantitative SAR (3D-QSAR), virtual screening, molecular docking, and molecular dynamics (MD) simulations. purine 211-217 cyclin dependent kinase 2 Homo sapiens 233-237 30396923-5 2018 The mechanism of cytotoxic action indicated that 7h caused significant (p<0.05) MDA-MB-231 cells arrest in the S phase as well as moderate cells arrest in the G2/M phase; confirmed by up-regulation of cyclins A/B1, p21 and CDKs 4/6, and down-regulation of cyclin E2 and CDK2 regulatory proteins. 7,8-diacetoxy-3-(4-nitrophenyl)coumarin 49-51 cyclin dependent kinase 2 Homo sapiens 273-277 30197029-2 2018 Here we reported the structure-based synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as CDK2 inhibitors, which exhibited potent CDK2 inhibitory activities, as well as anticancer activities in low concentration against two human cancer cell lines (MCF-7 and HCT116). 5,6-dihydropyrimido[4,5-f]quinazoline 82-119 cyclin dependent kinase 2 Homo sapiens 135-139 30197029-2 2018 Here we reported the structure-based synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as CDK2 inhibitors, which exhibited potent CDK2 inhibitory activities, as well as anticancer activities in low concentration against two human cancer cell lines (MCF-7 and HCT116). 5,6-dihydropyrimido[4,5-f]quinazoline 82-119 cyclin dependent kinase 2 Homo sapiens 175-179 29753773-0 2018 Synthesis, anticancer evaluation, and molecular docking studies of some novel 4,6-disubstituted pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 (CDK2) inhibitors. 4,6-disubstituted pyrazolo[3,4-d]pyrimidines 78-122 cyclin dependent kinase 2 Homo sapiens 126-151 29966874-0 2018 Design, synthesis and molecular modeling study of certain 4-Methylbenzenesulfonamides with CDK2 inhibitory activity as anticancer and radio-sensitizing agents. 4-toluenesulfonamide 58-85 cyclin dependent kinase 2 Homo sapiens 91-95 30106443-0 2018 Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. higenamine 0-10 cyclin dependent kinase 2 Homo sapiens 118-122 30106443-0 2018 Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. cucurbitacin B 45-59 cyclin dependent kinase 2 Homo sapiens 118-122 30106443-9 2018 The associated pathways were summarized by Kyoto Encyclopedia of Genes and Genomes pathway analysis, and it was hypothesized that higenamine may enhance the antitumor effects of Cu B in breast cancer through inhibition of the interaction of AKT and CDK2. higenamine 130-140 cyclin dependent kinase 2 Homo sapiens 249-253 29718700-4 2018 We found that the infiltration of IMAT was correlated with myostatin and phosphorylated CDK2 at tyrosine 15 [P-CDK2(Tyr15)]. Tyrosine 96-104 cyclin dependent kinase 2 Homo sapiens 88-92 29753773-3 2018 The structure-activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. thiophenethyl 79-92 cyclin dependent kinase 2 Homo sapiens 161-165 29753773-3 2018 The structure-activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. mono-substituted anilines 111-136 cyclin dependent kinase 2 Homo sapiens 161-165 29753773-3 2018 The structure-activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. 1-Pentanethiol 211-222 cyclin dependent kinase 2 Homo sapiens 161-165 29753773-3 2018 The structure-activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. di-substituted anilines 235-258 cyclin dependent kinase 2 Homo sapiens 161-165 29753773-4 2018 In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. 2-chloro 32-40 cyclin dependent kinase 2 Homo sapiens 149-153 30510740-2 2018 This study investigated the effect of the ethyl acetate fraction from O. japonicus extract (OJE) on the growth inhibition of OVCAR-3 human ovarian cancer cells demonstrated to inhibit cell growth and arrest the cell cycle in OVCAR-3 cells by blocking the sub-G1 phase and decreasing cyclin E1/CDK2 expression. ethyl acetate 42-55 cyclin dependent kinase 2 Homo sapiens 293-297 30349650-6 2018 Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. selinexor 20-29 cyclin dependent kinase 2 Homo sapiens 86-90 30015921-8 2018 Expression of p21 and p27 was upregulated, while cyclin E and CDK2 were downregulated in UPA-treated primary-cultured leiomyoma cells. ulipristal acetate 89-92 cyclin dependent kinase 2 Homo sapiens 62-66 30214601-8 2018 Western blot and reverse transcription-quantitative polymerase chain reaction analyses suggested that chaetominine treatment facilitated the expression of p53, p21, checkpoint kinase 2 (Chk2) and phosphorylated ataxia telangiectasia mutated (p-ATM) and caused a reduction in the mRNA levels of cyclin E and cyclin-dependent kinases (CDKs) 2 and 4. chaetominine 102-114 cyclin dependent kinase 2 Homo sapiens 333-337 29753773-4 2018 In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. Roxarsone 42-49 cyclin dependent kinase 2 Homo sapiens 149-153 29753773-0 2018 Synthesis, anticancer evaluation, and molecular docking studies of some novel 4,6-disubstituted pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 (CDK2) inhibitors. 4,6-disubstituted pyrazolo[3,4-d]pyrimidines 78-122 cyclin dependent kinase 2 Homo sapiens 153-157 29753773-4 2018 In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. 4-methylthio aniline 54-74 cyclin dependent kinase 2 Homo sapiens 149-153 29701267-6 2018 Costunolide inhibited proliferation by inducing cell cycle arrest in the G2 /M phase by decreasing cyclin B1 and cyclin-dependent kinase 2 expression and increasing p21 expression. costunolide 0-11 cyclin dependent kinase 2 Homo sapiens 113-138 29687635-0 2018 Imidazo[1,2-c]pyrimidin-5(6H)-one as a novel core of cyclin-dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring. 3,N(4)-ethanocytosine 0-33 cyclin dependent kinase 2 Homo sapiens 53-78 29654697-3 2018 Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Melatonin 13-22 cyclin dependent kinase 2 Homo sapiens 49-53 29767460-0 2018 Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation. pyrimidine-based pyrazoles 0-26 cyclin dependent kinase 2 Homo sapiens 30-55 29767460-1 2018 A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. pyrimidine-pyrazole 16-35 cyclin dependent kinase 2 Homo sapiens 84-109 29752478-4 2018 Western blot and real-time qPCR analysis revealed that bafilomycin C1 caused partial G0/G1 phase cell-cycle arrest, downregulated the expression of cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and upregulated the expression of p21. bafilomycin C1 55-69 cyclin dependent kinase 2 Homo sapiens 170-174 29687635-1 2018 We report on the synthesis, activity testing, docking, and quantum mechanical scoring of novel imidazo[1,2-c]pyrimidin-5(6H)-one scaffold for cyclin-dependent kinase 2 (CDK2) inhibition. 3,N(4)-ethanocytosine 95-128 cyclin dependent kinase 2 Homo sapiens 142-167 29687635-1 2018 We report on the synthesis, activity testing, docking, and quantum mechanical scoring of novel imidazo[1,2-c]pyrimidin-5(6H)-one scaffold for cyclin-dependent kinase 2 (CDK2) inhibition. 3,N(4)-ethanocytosine 95-128 cyclin dependent kinase 2 Homo sapiens 169-173 29687635-4 2018 The binding modes of the compounds obtained using Glide docking have exhibited up to 2 hinge-region hydrogen bonds to CDK2 and differed in the orientation of the inhibitor core and the placement of the 8-substituents. Hydrogen 100-108 cyclin dependent kinase 2 Homo sapiens 118-122 30250647-5 2018 Because flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor, we found significantly higher CDK1 and CDK2 mRNA expression in three independent cohorts human ACC (p<0.01) and CDK1 protein by immunohistochemistry (p<0.01) in human ACC samples. alvocidib 8-20 cyclin dependent kinase 2 Homo sapiens 113-117 29767250-2 2018 In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC-3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0-G1 phases of the cell cycle). diosmetin 192-201 cyclin dependent kinase 2 Homo sapiens 246-250 29101605-5 2018 At the same time, insulin and BaP also stimulated the expression of cell cycle proteins viz., Cyclin E and Cdk2, and thus induced more incorporation of Bromodeoxyuridine (BrdU) in cultured cells indicating increased DNA synthesis. benzylaminopurine 30-33 cyclin dependent kinase 2 Homo sapiens 107-111 29907572-9 2018 p17 interacts with cyclins by its cyclin-binding motif, 125RXL127 Sequence and mutagenic analyses of p17 indicated that a 140WXFD143 motif and residues Asp-113 and Lys-122 in p17 are critical for CDK2 and CDK6 binding, leading to their sequestration in the cytoplasm. Aspartic Acid 152-155 cyclin dependent kinase 2 Homo sapiens 196-200 29907572-9 2018 p17 interacts with cyclins by its cyclin-binding motif, 125RXL127 Sequence and mutagenic analyses of p17 indicated that a 140WXFD143 motif and residues Asp-113 and Lys-122 in p17 are critical for CDK2 and CDK6 binding, leading to their sequestration in the cytoplasm. Lysine 164-167 cyclin dependent kinase 2 Homo sapiens 196-200 29533214-8 2018 In addition, treatment of breast cancer cells with J1 revealed that, in contrast to the expression of cyclin B1, this curcumin analogue vigorously decreased the expression of cyclin A, CDK2 and cyclin E and subsequently sensitized tumor cells to cell cycle arrest. Curcumin 118-126 cyclin dependent kinase 2 Homo sapiens 185-189 29663555-7 2018 Dehydroleucodine arrested the cell cycle at the G0 /G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). dehydroleucodine 0-16 cyclin dependent kinase 2 Homo sapiens 137-141 30035169-0 2018 Targeting p27 tyrosine phosphorylation as a modality to inhibit CDK4 and CDK2 and cause cell cycle arrest in breast cancer cells. Tyrosine 14-22 cyclin dependent kinase 2 Homo sapiens 73-77 29709426-7 2018 While knock-outing STIM1 by CRISPR-CAS9 in 16HBE or inhibiting STIM1 mediated SOCE activation ameliorated cell death caused by acute PQ treatment, which also leaded to alleviating the cell accumulation in S phase through the modulation the expression of cyclinD1, p21, cyclinA2 and CDK2. Paraquat 133-135 cyclin dependent kinase 2 Homo sapiens 282-286 29655853-17 2018 Further study showed that TSAC significantly down-regulated the expressions of cyclin A, cyclin E and CDK2 in HepG2 cells. tsac 26-30 cyclin dependent kinase 2 Homo sapiens 102-106 29778287-6 2018 PGG affected cell-cycle- or apoptosis-related proteins such as cyclin E, CDK2, and Bcl-2, cleaved caspase-3. beta-penta-O-galloyl-glucose 0-3 cyclin dependent kinase 2 Homo sapiens 73-77 29853338-0 2018 Design, synthesis and biological evaluation of pyrimidine derivatives as novel CDK2 inhibitors that induce apoptosis and cell cycle arrest in breast cancer cells. pyrimidine 47-57 cyclin dependent kinase 2 Homo sapiens 79-83 29853338-4 2018 In this article, 24 benzamide derivatives were designed, synthesized and investigated for the inhibition activity against CDK2. benzamide 20-29 cyclin dependent kinase 2 Homo sapiens 122-126 30011295-3 2018 Arecoline arrested preadipocyte growth in the G2/M phase of the cell cycle; decreased the total levels of cyclin-dependent kinase 1 (CDK1), p21, and p27 proteins; increased p53 and cyclin B1 protein levels; and had no effect on CDK2 protein levels. Arecoline 0-9 cyclin dependent kinase 2 Homo sapiens 228-232 29665367-7 2018 Taken together, our results indicate that TSWU-CD4 induces S phase arrest by inhibiting Akt-mediated HDAC3 expression and CDK2 Thr 39 phosphorylation to suppress the formation of cyclin A-p-CDK2 (Thr 39) complexes. Threonine 196-199 cyclin dependent kinase 2 Homo sapiens 190-194 29665367-0 2018 Suppression of Akt-mediated HDAC3 expression and CDK2 T39 phosphorylation by a bichalcone analog contributes to S phase retardation of cancer cells. rhuschalcone-1 79-89 cyclin dependent kinase 2 Homo sapiens 49-53 29665367-3 2018 Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest. Threonine 71-74 cyclin dependent kinase 2 Homo sapiens 22-26 29665367-3 2018 Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest. Threonine 71-74 cyclin dependent kinase 2 Homo sapiens 89-93 29665367-3 2018 Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest. Threonine 71-74 cyclin dependent kinase 2 Homo sapiens 89-93 29665367-2 2018 We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. rhuschalcone-1 24-34 cyclin dependent kinase 2 Homo sapiens 175-179 29665367-4 2018 Decreased histone deacetylase 3 (HDAC3) expression after TSWU-CD4 treatment was demonstrated, and TSWU-CD4 induced S phase arrest and inhibitory effects on cyclin A expression and CDK2 Thr 39 phosphorylation, while cyclin A-p-CDK2 (Thr 39) complex formation was suppressed by ectopic wild-type HDAC3 expression. Threonine 185-188 cyclin dependent kinase 2 Homo sapiens 180-184 29665367-2 2018 We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Threonine 181-190 cyclin dependent kinase 2 Homo sapiens 175-179 29890691-8 2018 Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Curcumin 112-120 cyclin dependent kinase 2 Homo sapiens 0-25 29665367-2 2018 We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Threonine 192-195 cyclin dependent kinase 2 Homo sapiens 175-179 29665367-5 2018 The co-transfection of CDK2 (T39E) along with HDAC3 completely restored cyclin A expression, Thr 39-phosphorylated CDK2, cyclin A-p-CDK2 (Thr 39) complex formation, and the S phase population to normal levels. Threonine 93-96 cyclin dependent kinase 2 Homo sapiens 23-27 29665367-5 2018 The co-transfection of CDK2 (T39E) along with HDAC3 completely restored cyclin A expression, Thr 39-phosphorylated CDK2, cyclin A-p-CDK2 (Thr 39) complex formation, and the S phase population to normal levels. Threonine 138-141 cyclin dependent kinase 2 Homo sapiens 23-27 29665367-7 2018 Taken together, our results indicate that TSWU-CD4 induces S phase arrest by inhibiting Akt-mediated HDAC3 expression and CDK2 Thr 39 phosphorylation to suppress the formation of cyclin A-p-CDK2 (Thr 39) complexes. Threonine 127-130 cyclin dependent kinase 2 Homo sapiens 122-126 29890691-8 2018 Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Curcumin 112-120 cyclin dependent kinase 2 Homo sapiens 27-31 29890691-9 2018 Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Curcumin 13-21 cyclin dependent kinase 2 Homo sapiens 74-78 29890691-10 2018 Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. Curcumin 100-108 cyclin dependent kinase 2 Homo sapiens 92-96 29708285-0 2018 Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors. 3h-imidazole[4,5-c]pyridine 50-77 cyclin dependent kinase 2 Homo sapiens 93-97 29708285-1 2018 A novel series of imidazo[4,5-c]pyridine-based CDK2 inhibitors were designed from the structure of CYC202 via scaffold hopping strategy. 3H-Imidazo[4,5-c]pyridine 18-40 cyclin dependent kinase 2 Homo sapiens 47-51 29708285-6 2018 Therefore, the pyridin-3-ylmethyl moiety would serve as an excellent pharmacophore for the development of novel CDK2 inhibitors for targeted anti-cancer therapy. pyridin-3-ylmethyl 15-33 cyclin dependent kinase 2 Homo sapiens 112-116 29751524-8 2018 Additionally, beta-asarone modulated the cell cycle-related proteins p21, p27, Cdc25A, cyclin D, cyclin E, and CDK2. asarone 14-26 cyclin dependent kinase 2 Homo sapiens 111-115 30003065-9 2018 DHTS induced cell cycle arrest in the G0/G1 phase, which was mediated by downregulation of cyclin D1, cyclin A, cyclin E, CDK4, CDK2, c-Myc and p-Rb expression and with increased expression of the CDK inhibitor p21. dhts 0-4 cyclin dependent kinase 2 Homo sapiens 128-132 29928364-9 2018 Decreased chemosensitivity to cisplatin may be associated with increased expression of phosphorylated-protein kinase B and cyclin dependent kinase 2 and with decreased expression of p21 and the B cell lymphoma (Bcl)-2 associated X/Bcl-2 ratio. Cisplatin 30-39 cyclin dependent kinase 2 Homo sapiens 123-148 29792216-1 2018 BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Serine 103-106 cyclin dependent kinase 2 Homo sapiens 84-88 29792216-1 2018 BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Serine 136-139 cyclin dependent kinase 2 Homo sapiens 84-88 29792216-4 2018 In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Serine 57-60 cyclin dependent kinase 2 Homo sapiens 10-14 29792216-4 2018 In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Serine 76-79 cyclin dependent kinase 2 Homo sapiens 10-14 29792216-6 2018 Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Serine 23-26 cyclin dependent kinase 2 Homo sapiens 101-105 28833099-0 2018 Simvastatin induces G1 arrest by up-regulating GSK3beta and down-regulating CDK4/cyclin D1 and CDK2/cyclin E1 in human primary colorectal cancer cells. Simvastatin 0-11 cyclin dependent kinase 2 Homo sapiens 95-99 28833099-7 2018 SIM suppressed cell growth and induced cell cycle G1 -arrest by suppressing the expression of CDK4/cyclin D1 and CDK2/cyclin E1, but elevating the expression of glycogen synthase kinase 3beta in CPs. Simvastatin 0-3 cyclin dependent kinase 2 Homo sapiens 113-117 29762502-4 2018 Flow cytometric assay displayed that polyphyllin VI promoted the generation of reactive oxygen species (ROS), depolarized the mitochondrial membrane potential (MMP), and induced S phase cell cycle arrest by decreasing the expression of cyclin A2 and CDK2, while significantly increasing the expression of p21 protein. Polyphyllin VI 37-51 cyclin dependent kinase 2 Homo sapiens 250-254 29550093-0 2018 Discovery of novel CDK inhibitors via scaffold hopping from CAN508. CAN 508 60-66 cyclin dependent kinase 2 Homo sapiens 19-22 29550093-2 2018 Scaffold hopping strategy was applied on CAN508, a known selective CDK9 inhibitor, and a series of pyrazolo[3,4-b]pyridine compounds were synthesized and evaluated in vitro as CDK2 and CDK9 inhibitors. pyrazolo(3,4-b)pyridine 99-122 cyclin dependent kinase 2 Homo sapiens 176-180 29377076-3 2018 Here we show that the CDK2 inhibitor, purvalanol A, induces a rapid decrease in myeloid cell leukaemia factor-1 (Mcl-1) levels in human neutrophils and peripheral blood mononuclear cells (PBMCs), but only induces apoptosis in neutrophils which are dependent upon expression on this protein for survival. 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine 38-50 cyclin dependent kinase 2 Homo sapiens 22-26 29421751-6 2018 Treatment with 17 TB increased the expression of cell cycle regulatory proteins, cyclin D2/CDK-4 and cyclin E/CDK-2, whereas the expression of p27 was down-regulated. Terbium 18-20 cyclin dependent kinase 2 Homo sapiens 110-115 29629444-2 2018 HSD992, containing a novel scaffold based on the tetrahydro-3H-pyrazolo[4,3-a]phenanthridine core, inhibits CDK2/3 but not other CDKs and also potently inhibits several cancer cell lines. tetrahydro-3h-pyrazolo[4,3-a]phenanthridine 49-92 cyclin dependent kinase 2 Homo sapiens 108-112 29377076-4 2018 This rapid decrease in cellular Mcl-1 protein levels was due to a purvalanol A-induced decrease in stability, with the half-life of the protein decreasing from approximately 2 h in control cells to just over 1 h after addition of the CDK2 inhibitor: it also blocked the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent stabilization of Mcl-1. 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine 66-78 cyclin dependent kinase 2 Homo sapiens 234-238 29032312-0 2018 Advanced oxidation protein products induce S-phase arrest of hepatocytes via the ROS-dependent, beta-catenin-CDK2-mediated pathway. Reactive Oxygen Species 81-84 cyclin dependent kinase 2 Homo sapiens 109-113 29725405-6 2018 Consistently, there was a significant decrease in the expression of cell proliferation-associated proteins, including cyclin D1, cyclin-dependent kinase (Cdk)2 and Cdk4 in A431 cells treated with rosiglitazone. Rosiglitazone 196-209 cyclin dependent kinase 2 Homo sapiens 129-159 29682280-0 2018 SAR study on N2,N4-disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents. n2,n4-disubstituted pyrimidine-2,4-diamines 13-56 cyclin dependent kinase 2 Homo sapiens 70-74 29682280-2 2018 A series of N2,N4-diphenylpyrimidine-2,4-diamines were previously identified as potent CDK2/CDK9 inhibitors. n2,n4-diphenylpyrimidine-2,4-diamines 12-49 cyclin dependent kinase 2 Homo sapiens 87-91 29393481-9 2018 After treatment with PGD, the expression of TIMP-1, CDK2, cyclin A and cyclin E was reduced at the protein level. pgd 21-24 cyclin dependent kinase 2 Homo sapiens 52-56 29032312-11 2018 This study provides preliminary evidence that AOPP can induce S-phase arrest in hepatocytes via the ROS-dependent, beta-catenin-CDK2-mediated pathway. Reactive Oxygen Species 100-103 cyclin dependent kinase 2 Homo sapiens 128-132 29507054-6 2018 The CDK2 inhibitor, dinaciclib, attenuated resistance to both classes of inhibitors and combinations thereof. dinaciclib 20-30 cyclin dependent kinase 2 Homo sapiens 4-8 29744291-6 2018 Cyclin-dependent kinase 2 (CDK2) was positively regulated by PCBP2 via a direct 3" UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. Biotin 175-181 cyclin dependent kinase 2 Homo sapiens 0-25 29744291-6 2018 Cyclin-dependent kinase 2 (CDK2) was positively regulated by PCBP2 via a direct 3" UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. Biotin 175-181 cyclin dependent kinase 2 Homo sapiens 27-31 29157894-0 2018 Selective inhibition reveals cyclin-dependent kinase 2 as another kinase that phosphorylates the androgen receptor at serine 81. Serine 118-124 cyclin dependent kinase 2 Homo sapiens 29-54 29629344-10 2018 The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. esculetin 137-146 cyclin dependent kinase 2 Homo sapiens 77-81 29363886-3 2018 Treatment of two OSCC cell lines with honokiol resulted in reducing the cell proliferation and arresting the cell cycle at G1 stage which was correlated with the down-regulation of Cdk2 and Cdk4 and the up-regulation of cell cycle suppressors, p21 and p27. honokiol 38-46 cyclin dependent kinase 2 Homo sapiens 181-185 29063678-5 2018 X-ray crystallography studies reveal that hydrogen bonding with the DFG motif of CDK2 is the likely mechanism of greater enzymatic potency. Hydrogen 42-50 cyclin dependent kinase 2 Homo sapiens 81-85 29063678-5 2018 X-ray crystallography studies reveal that hydrogen bonding with the DFG motif of CDK2 is the likely mechanism of greater enzymatic potency. 1,3-Diphenylguanidine 68-71 cyclin dependent kinase 2 Homo sapiens 81-85 29330290-10 2018 The use of ALT demonstrates that both CDK4 and CDK2 need to be inhibited if long-term efficacy is to be achieved and represents a novel modality to inhibit breast cancer cells.Implications: Modulating tyrosine phosphorylation of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in breast cancer and suggests that phospho-p27 status may serve as a biomarker for patients that are responsive to CDK4/6 inhibition. Tyrosine 201-209 cyclin dependent kinase 2 Homo sapiens 47-51 29330290-10 2018 The use of ALT demonstrates that both CDK4 and CDK2 need to be inhibited if long-term efficacy is to be achieved and represents a novel modality to inhibit breast cancer cells.Implications: Modulating tyrosine phosphorylation of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in breast cancer and suggests that phospho-p27 status may serve as a biomarker for patients that are responsive to CDK4/6 inhibition. Tyrosine 201-209 cyclin dependent kinase 2 Homo sapiens 283-287 29507054-7 2018 Notably, we found that MITF expression correlates with CDK2 upregulation in patients; thus, dinaciclib would warrant consideration for treatment of patients unresponsive to BRAF-MEK and/or Hsp90 inhibitors and/or harboring MITF amplification/overexpression. dinaciclib 92-102 cyclin dependent kinase 2 Homo sapiens 55-59 29063678-3 2018 We describe herein the molecular and cellular effects of CCT068127, a novel inhibitor of CDK2 and CDK9. CCT68127 57-66 cyclin dependent kinase 2 Homo sapiens 89-93 29330290-0 2018 Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells. Tyrosine 51-59 cyclin dependent kinase 2 Homo sapiens 28-32 29330290-4 2018 In addition, a novel strategy is described to inhibit tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2 and CDK4. Tyrosine 54-62 cyclin dependent kinase 2 Homo sapiens 131-135 29253178-2 2018 Here, we focus our analysis on PCBP-controlled cassette exon-splicing within the cell cycle control regulator cyclin-dependent kinase-2 (CDK2) transcript. pcbp 31-35 cyclin dependent kinase 2 Homo sapiens 110-135 29253178-2 2018 Here, we focus our analysis on PCBP-controlled cassette exon-splicing within the cell cycle control regulator cyclin-dependent kinase-2 (CDK2) transcript. pcbp 31-35 cyclin dependent kinase 2 Homo sapiens 137-141 29253178-3 2018 We demonstrate that PCBP binding to a C-rich polypyrimidine tract (PPT) preceding exon 5 of the CDK2 transcript enhances cassette exon inclusion. pcbp 20-24 cyclin dependent kinase 2 Homo sapiens 96-100 29253178-5 2018 Remarkably, PCBPs" control of CDK2 ex5 splicing has evolved subsequent to mammalian divergence via conversion of constitutive exon 5 inclusion in the mouse CDK2 transcript to PCBP-responsive exon 5 alternative splicing in humans. pcbps 12-17 cyclin dependent kinase 2 Homo sapiens 30-34 29253178-5 2018 Remarkably, PCBPs" control of CDK2 ex5 splicing has evolved subsequent to mammalian divergence via conversion of constitutive exon 5 inclusion in the mouse CDK2 transcript to PCBP-responsive exon 5 alternative splicing in humans. pcbp 12-16 cyclin dependent kinase 2 Homo sapiens 30-34 29483845-12 2018 A rescue in the expression of both MLL genes was observed in KCL22S, a CML cell line sensitive to IM, after treatment with dasatinib or nilotinib which was associated with a higher rate of apoptosis, an enhanced expression of p21 (CDKN1A) and a concomitant decrease in the expression of CDK2, CDK4 and Cyclin B1 (CCNB1) in comparison to untreated KCL22S control or IM resistant KCL22R cell line, which suggests involvement of p53 regulated pathway. Dasatinib 123-132 cyclin dependent kinase 2 Homo sapiens 287-291 29483845-12 2018 A rescue in the expression of both MLL genes was observed in KCL22S, a CML cell line sensitive to IM, after treatment with dasatinib or nilotinib which was associated with a higher rate of apoptosis, an enhanced expression of p21 (CDKN1A) and a concomitant decrease in the expression of CDK2, CDK4 and Cyclin B1 (CCNB1) in comparison to untreated KCL22S control or IM resistant KCL22R cell line, which suggests involvement of p53 regulated pathway. nilotinib 136-145 cyclin dependent kinase 2 Homo sapiens 287-291 29483845-12 2018 A rescue in the expression of both MLL genes was observed in KCL22S, a CML cell line sensitive to IM, after treatment with dasatinib or nilotinib which was associated with a higher rate of apoptosis, an enhanced expression of p21 (CDKN1A) and a concomitant decrease in the expression of CDK2, CDK4 and Cyclin B1 (CCNB1) in comparison to untreated KCL22S control or IM resistant KCL22R cell line, which suggests involvement of p53 regulated pathway. kcl22s 61-67 cyclin dependent kinase 2 Homo sapiens 287-291 29793319-6 2018 The results indicated that oroxyloside significantly suppressed the proliferation of human glioma cells through inducing cell cycle arrest at G0/G1 phase through reducing Cyclin D1 and cyclin-dependent kinase 2 (CDK2) while enhancing p53 and p21 expressions. oroxylin A-7-O-glucuronide 27-38 cyclin dependent kinase 2 Homo sapiens 185-210 29434878-10 2018 Moreover, PG treatment induced a shift of Herceptin-dependent cell cycle arrest in G1 phase towards S and G2 phases with concomitant upregulation of cyclin-dependent kinase 2 (CDK2) and downregulation of CDK inhibitor p27Kip1. Progesterone 10-12 cyclin dependent kinase 2 Homo sapiens 149-174 29434878-10 2018 Moreover, PG treatment induced a shift of Herceptin-dependent cell cycle arrest in G1 phase towards S and G2 phases with concomitant upregulation of cyclin-dependent kinase 2 (CDK2) and downregulation of CDK inhibitor p27Kip1. Progesterone 10-12 cyclin dependent kinase 2 Homo sapiens 176-180 29215867-7 2018 The AS-v-Cdks are functional and utilize different ATP derivatives with a specificity closely matching their cellular ortholog, AS-Cdk2. Adenosine Triphosphate 51-54 cyclin dependent kinase 2 Homo sapiens 9-13 29391779-10 2018 A molecular docking study of compound 5 showed that xanthone formed binding interactions with some receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation (COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor. xanthone 52-60 cyclin dependent kinase 2 Homo sapiens 203-228 29391779-10 2018 A molecular docking study of compound 5 showed that xanthone formed binding interactions with some receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation (COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor. xanthone 52-60 cyclin dependent kinase 2 Homo sapiens 230-234 28684297-13 2018 RT-qPCR and Western blot data showed that curcumol enhanced the expression of GSK3beta, P27, p21 and P16, and decreased the levels of PI3K, phosphorylated Akt (p-Akt), cyclin D1, CDK4, cyclin E and CDK2. curcumol 42-50 cyclin dependent kinase 2 Homo sapiens 198-202 29793319-6 2018 The results indicated that oroxyloside significantly suppressed the proliferation of human glioma cells through inducing cell cycle arrest at G0/G1 phase through reducing Cyclin D1 and cyclin-dependent kinase 2 (CDK2) while enhancing p53 and p21 expressions. oroxylin A-7-O-glucuronide 27-38 cyclin dependent kinase 2 Homo sapiens 212-216 29793319-9 2018 In vivo, oroxyloside administration significantly inhibited the glioma cell xenograft tumorigenesis through various signaling pathways, including suppression of Cyclin D1/CDK2 and ECM pathways, as well as potentiation of p53/p21 and Caspases pathways. oroxylin A-7-O-glucuronide 9-20 cyclin dependent kinase 2 Homo sapiens 171-175 29235893-7 2018 Simulation docking study was undertaken to gain insight into the possible binding mode of 13a in the CDK2 enzyme. 13a 90-93 cyclin dependent kinase 2 Homo sapiens 101-105 30039733-2 2018 The S-phase kinase CDK2-cyclinA phosphorylates SAMHD1 at Thr-592. Threonine 57-60 cyclin dependent kinase 2 Homo sapiens 19-23 30101722-8 2018 After treatment with paclitaxel, cyclin D1 and CDK4 protein levels were similar to control values; meanwhile, cylinE1 and CDK2 protein amounts were reduced, with increased cyclin B1 levels, compared with control values (p<0.05). Paclitaxel 21-31 cyclin dependent kinase 2 Homo sapiens 122-126 28585698-4 2018 Results showed that lycopene pretreatment attenuated UVB-induced cell hyper-proliferation and promoted apoptosis, accompanied by decreased cyclin-dependent kinase 2 (CDK2) and CDK4 complex in both human keratinocytes and SKH-1 hairless mice. Lycopene 20-28 cyclin dependent kinase 2 Homo sapiens 139-164 28585698-4 2018 Results showed that lycopene pretreatment attenuated UVB-induced cell hyper-proliferation and promoted apoptosis, accompanied by decreased cyclin-dependent kinase 2 (CDK2) and CDK4 complex in both human keratinocytes and SKH-1 hairless mice. Lycopene 20-28 cyclin dependent kinase 2 Homo sapiens 166-170 28585698-6 2018 Gene ablation of FOXO3a attenuated lycopene-induced decrease in cell hyper-proliferation, CDK2, and CDK4 complex, indicating a critical role of FOXO3a in the lycopene-induced anti-proliferative effect of keratinocytes during UVB irradiation. Lycopene 35-43 cyclin dependent kinase 2 Homo sapiens 90-94 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. alvocidib 133-145 cyclin dependent kinase 2 Homo sapiens 29-33 29312515-5 2017 The combination increased the acetylation levels of histone H3 and decreased HDAC activity in MDS cells.A low concentration (25 and 50 nM) of chidamide combined with low-dose cytarabine (50 nM) inhibited cell proliferation and arrested the cell cycle in the G0/G1 phasevia down-regulating CDK2 and up-regulating p21. N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide 142-151 cyclin dependent kinase 2 Homo sapiens 289-293 29312515-5 2017 The combination increased the acetylation levels of histone H3 and decreased HDAC activity in MDS cells.A low concentration (25 and 50 nM) of chidamide combined with low-dose cytarabine (50 nM) inhibited cell proliferation and arrested the cell cycle in the G0/G1 phasevia down-regulating CDK2 and up-regulating p21. Cytarabine 175-185 cyclin dependent kinase 2 Homo sapiens 289-293 29175378-0 2018 Increased activity of both CDK1 and CDK2 is necessary for the combinatorial activity of WEE1 inhibition and cytarabine. Cytarabine 108-118 cyclin dependent kinase 2 Homo sapiens 36-40 29175378-6 2018 Furthermore, pharmacologic inhibition of CDK1 alone or CDK1 and CDK2 together reduced the combinatorial activity of AZD1775 and cytarabine. adavosertib 116-123 cyclin dependent kinase 2 Homo sapiens 64-68 29175378-6 2018 Furthermore, pharmacologic inhibition of CDK1 alone or CDK1 and CDK2 together reduced the combinatorial activity of AZD1775 and cytarabine. Cytarabine 128-138 cyclin dependent kinase 2 Homo sapiens 64-68 29175378-7 2018 Thus, increased activity of both CDK1 and CDK2 in response to WEE1 inhibition is necessary for the combinatorial activity of AZD1775 and cytarabine. adavosertib 125-132 cyclin dependent kinase 2 Homo sapiens 42-46 29175378-7 2018 Thus, increased activity of both CDK1 and CDK2 in response to WEE1 inhibition is necessary for the combinatorial activity of AZD1775 and cytarabine. Cytarabine 137-147 cyclin dependent kinase 2 Homo sapiens 42-46 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. alvocidib 133-145 cyclin dependent kinase 2 Homo sapiens 45-49 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. alvocidib 133-145 cyclin dependent kinase 2 Homo sapiens 249-253 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. indirubicin 147-158 cyclin dependent kinase 2 Homo sapiens 29-33 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. indirubicin 147-158 cyclin dependent kinase 2 Homo sapiens 45-49 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. indirubicin 147-158 cyclin dependent kinase 2 Homo sapiens 249-253 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. Roscovitine 160-171 cyclin dependent kinase 2 Homo sapiens 29-33 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. Roscovitine 160-171 cyclin dependent kinase 2 Homo sapiens 45-49 28911822-2 2017 The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. Roscovitine 160-171 cyclin dependent kinase 2 Homo sapiens 249-253 28911822-4 2017 Computer-aided drug design (CADD) tools added a benefit to the design and development of new CDK inhibitors by studying the binding pattern of the inhibitors to the ATP binding domain of CDKs. Adenosine Triphosphate 165-168 cyclin dependent kinase 2 Homo sapiens 187-191 28911822-5 2017 Herein, we have attempted a comparative analysis of structural differences between several CDKs ATP binding sites and their inhibitor specificity by depicting the important ligand-receptor interactions for a particular CDK to be targeted. Adenosine Triphosphate 96-99 cyclin dependent kinase 2 Homo sapiens 91-95 29031202-5 2017 We showed that niclosamide could inhibit OSCC cells proliferation through causing cell cycle arrest in G1 phase and promoting apoptosis, while the cell cycle-related proteins MCM2, MCM7, CDK2 and CDK4 were downregulated and the apoptosis-related proteins p53 and cleaved caspase-3 were upregulated. Niclosamide 15-26 cyclin dependent kinase 2 Homo sapiens 187-191 28911860-7 2017 Conversely, VRK1 self-represses its activity to phosphorylate PXR through cyclin-dependent kinase 2 (CDK2) in high glucose conditions, resulting in the repression of the PCK1 gene. Glucose 115-122 cyclin dependent kinase 2 Homo sapiens 74-99 28911860-7 2017 Conversely, VRK1 self-represses its activity to phosphorylate PXR through cyclin-dependent kinase 2 (CDK2) in high glucose conditions, resulting in the repression of the PCK1 gene. Glucose 115-122 cyclin dependent kinase 2 Homo sapiens 101-105 28911860-9 2017 Thus, the VRK1-CDK2-PXR-PP2Calpha-SGK2 pathway can be a novel physiological cell signaling that regulates gluconeogenesis in response to glucose. Glucose 137-144 cyclin dependent kinase 2 Homo sapiens 15-19 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. lmw-e 0-5 cyclin dependent kinase 2 Homo sapiens 60-64 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. dinaciclib 112-122 cyclin dependent kinase 2 Homo sapiens 104-108 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. dinaciclib 112-122 cyclin dependent kinase 2 Homo sapiens 104-108 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. lmw-e 132-137 cyclin dependent kinase 2 Homo sapiens 104-108 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. lmw-e 132-137 cyclin dependent kinase 2 Homo sapiens 104-108 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. lmw-e 132-137 cyclin dependent kinase 2 Homo sapiens 104-108 28947566-7 2017 LMW-E expression overcame cell-cycle inhibition by AIs in a CDK2/Rb-dependent manner, and inhibition of CDK2 by dinaciclib reversed LMW-E-mediated resistance, whereas treatment with palbociclib, a CDK4/6 inhibitor, did not.Conclusions: Collectively, these findings suggest that cell-cycle deregulation by LMW-E mediates resistance to AIs and a combination of CDK2 inhibitors and AIs may be an effective treatment in patients with HR-positive tumors that express LMW-E. Clin Cancer Res; 23(23); 7288-300. lmw-e 132-137 cyclin dependent kinase 2 Homo sapiens 104-108 29372687-0 2017 Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737. SU 9516 36-42 cyclin dependent kinase 2 Homo sapiens 0-25 29372687-2 2017 The aim of presented study was to determine the effect of ABT-737 inhibitor of anti-apoptotic proteins Bcl-2, Bcl-XL and Bcl-w as well as cyclin-dependent kinase 2 (CDK2) inhibitor SU9516 alone and in combination with ABT-737 on survival of colorectal cell lines HT29 and Caco-2. SU 9516 181-187 cyclin dependent kinase 2 Homo sapiens 138-163 29254203-0 2017 Inhibition of STAT3/VEGF/CDK2 axis signaling is critically involved in the antiangiogenic and apoptotic effects of arsenic herbal mixture PROS in non-small lung cancer cells. Arsenic 115-122 cyclin dependent kinase 2 Homo sapiens 25-29 28946186-4 2017 Mechanistic study revealed that Cryptotanshinone suppressed the expression of p-STAT3, Bcl-2, CDK2, Snail and MMP2, and induced the expression of E-cadherin, P53, P21 and beta-catenin. cryptotanshinone 32-48 cyclin dependent kinase 2 Homo sapiens 94-98 29254203-3 2017 PROS exerted significant cytotoxicity, induced sub-G1 phase and S phase arrest, increased apoptotic bodies, and attenuated the expression of pro-PARP, Bcl-2, Cyclin E, Cyclin A, CDK2, E2F1, p-Src, p-STAT3, p-ERK, p-AKT, COX-2 and SOCS-1 in A549 and H460 cells along with disrupted binding of STAT3 with CDK2 or VEGF. Proline 0-4 cyclin dependent kinase 2 Homo sapiens 178-182 29254203-3 2017 PROS exerted significant cytotoxicity, induced sub-G1 phase and S phase arrest, increased apoptotic bodies, and attenuated the expression of pro-PARP, Bcl-2, Cyclin E, Cyclin A, CDK2, E2F1, p-Src, p-STAT3, p-ERK, p-AKT, COX-2 and SOCS-1 in A549 and H460 cells along with disrupted binding of STAT3 with CDK2 or VEGF. Proline 0-4 cyclin dependent kinase 2 Homo sapiens 303-307 28849118-6 2017 Western blotting demonstrated K-Ras-p110alpha interaction was required for the effects of aspirin-induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). Aspirin 90-97 cyclin dependent kinase 2 Homo sapiens 209-234 28291626-7 2017 Mus81 knockdown also induced S phase arrest and elevated apoptosis in CDDP treated HCT116 cells through activating CHK1/CDC25A/CDK2 and CHK1/p53/Bax pathways, while these effects could be counteracted by CHK1 inhibition. Cisplatin 70-74 cyclin dependent kinase 2 Homo sapiens 127-131 28300289-3 2017 Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK1) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells. Lactones 14-21 cyclin dependent kinase 2 Homo sapiens 82-107 28300289-3 2017 Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK1) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells. Lactones 14-21 cyclin dependent kinase 2 Homo sapiens 109-113 28835467-8 2017 Rad18-/- and Polkappa-/- cells were highly sensitive to the WEE1 inhibitor MK-1775 (which simultaneously activates CDK2 and abrogates the G2/M checkpoint). adavosertib 75-82 cyclin dependent kinase 2 Homo sapiens 115-119 28757460-6 2017 Olaquindox could induce S-phase arrest in HepG2 cells involved with the increase of Cyclin A, Cyclin E and CDK 2. olaquindox 0-10 cyclin dependent kinase 2 Homo sapiens 107-112 28849118-6 2017 Western blotting demonstrated K-Ras-p110alpha interaction was required for the effects of aspirin-induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). Aspirin 90-97 cyclin dependent kinase 2 Homo sapiens 236-240 28677808-6 2017 Additionally, IMBP potentiated the therapeutic efficacy of doxorubicin-based breast cancer chemotherapy via the activation of cell cycle arrest and cell apoptosis pathway genes including p53, p21, CDK2, cyclin A, caspase 9, Bcl-2 and Bax. Doxorubicin 59-70 cyclin dependent kinase 2 Homo sapiens 197-201 28934491-4 2017 Here we report that poleta is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. Serine 134-140 cyclin dependent kinase 2 Homo sapiens 53-57 28827110-2 2017 A series of novel 6-aminopurine compounds was prepared for structure-activity relationship (SAR) studies of CDK2 and CDK5 inhibitors. Adenine 18-31 cyclin dependent kinase 2 Homo sapiens 108-112 28827110-4 2017 Here, we report the synthesis and evaluation of novel 6-aminopurine derivatives and present molecular docking models of compound 81 with CDK2 and CDK5. Adenine 54-67 cyclin dependent kinase 2 Homo sapiens 137-141 28790461-5 2017 CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. cape-pno2 0-9 cyclin dependent kinase 2 Homo sapiens 171-175 28790461-5 2017 CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. cape-pno2 104-113 cyclin dependent kinase 2 Homo sapiens 171-175 28726723-8 2017 Indeed, a reduction of the cellular level of cyclin-dependent kinases CDK2 and CDK4 was observed in mertensene-treated cells. Mertensene 100-110 cyclin dependent kinase 2 Homo sapiens 70-74 28501424-3 2017 RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). ro0504985 0-9 cyclin dependent kinase 2 Homo sapiens 54-79 28501424-3 2017 RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). ro0504985 0-9 cyclin dependent kinase 2 Homo sapiens 81-85 28501424-4 2017 However, using kinase selectivity assays it was found that RO0504985 was an inhibitor of several CMGC group kinase proteins, including CDK2. ro0504985 59-68 cyclin dependent kinase 2 Homo sapiens 135-139 28823273-6 2017 In addition, DATS treatment could significantly induce the G1/S arrest and suppress the expression of cyclin D1, cyclin E, CDK2 and CDK4. allicin 13-17 cyclin dependent kinase 2 Homo sapiens 123-127 28823273-7 2017 CONCLUSION: DATS can inhibit the proliferation and colony-forming of SP cells in multiple myeloma, and induce the G1/S arrest that may be carried out via suppressing the expression of cyclin D1, cyclin E, CDK2 and CDK4. allicin 12-16 cyclin dependent kinase 2 Homo sapiens 205-209 28726150-0 2017 Inhibition mechanism of CDK-2 and GSK-3beta by a sulfamoylphenyl derivative of indoline-a molecular dynamics study. indoline-a 79-89 cyclin dependent kinase 2 Homo sapiens 24-29 28318508-6 2017 TBMEHP induced a marked G0/G1 cell cycle arrest and robust cell apoptosis at 1mug/mL by inducing expression of p53, GADD45alpha and cyclin dependent kinase (CDK) inhibitors (p21and p27) while suppressing the expression of cyclin D1, CDK2, CDK6, and Bcl-2. tbmehp 0-6 cyclin dependent kinase 2 Homo sapiens 157-160 28251795-4 2017 Quercetin-induced G0 /G1 -phase arrest occurred when expressions of cyclin-dependent kinase (CDK)2/4 were inhibited and the CDK inhibitors, p16 and p21, were induced. Quercetin 0-9 cyclin dependent kinase 2 Homo sapiens 93-98 28720813-4 2017 Mechanistically, daphnegiravone D induced G0/G1 arrest and apoptosis, reduced the expression of cyclin E1, CDK2 and CDK4, and promoted the cleavage of caspase 3 and PARP in Hep3B and HepG2 cells. daphnegiravone 17-31 cyclin dependent kinase 2 Homo sapiens 107-111 28318508-6 2017 TBMEHP induced a marked G0/G1 cell cycle arrest and robust cell apoptosis at 1mug/mL by inducing expression of p53, GADD45alpha and cyclin dependent kinase (CDK) inhibitors (p21and p27) while suppressing the expression of cyclin D1, CDK2, CDK6, and Bcl-2. tbmehp 0-6 cyclin dependent kinase 2 Homo sapiens 233-237 28318508-7 2017 Unlike TBMEHP, TBPH caused early apoptosis after G2/M phase arrest only at 10mug/mL via up-regulation of p21 and down-regulation of CDK2 and CDK4. bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate 15-19 cyclin dependent kinase 2 Homo sapiens 132-136 28506552-7 2017 In addition, alpha-terthienylmethanol induced a change in S phase-related proteins cyclin A, cyclin-dependent kinase 2, and cyclin D2. alpha-terthienylmethanol 13-37 cyclin dependent kinase 2 Homo sapiens 93-118 28693160-1 2017 The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). isoliquiritigenin 183-200 cyclin dependent kinase 2 Homo sapiens 71-96 28693160-1 2017 The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). isoliquiritigenin 183-200 cyclin dependent kinase 2 Homo sapiens 98-102 28693160-1 2017 The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). isoliquiritigenin 202-205 cyclin dependent kinase 2 Homo sapiens 71-96 28693160-1 2017 The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). isoliquiritigenin 202-205 cyclin dependent kinase 2 Homo sapiens 98-102 28693160-12 2017 MK-8776 (an inhibitor of CDK2) antagonized the apoptosis induced by ISL, and, compared with treatment with ISL alone, pretreatment with MK-8776 inhibited the decrease in DeltaPsim, downregulated the mRNA expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, and upregulated Bcl-2 mRNA expression. MK-8776 0-7 cyclin dependent kinase 2 Homo sapiens 25-29 28693160-12 2017 MK-8776 (an inhibitor of CDK2) antagonized the apoptosis induced by ISL, and, compared with treatment with ISL alone, pretreatment with MK-8776 inhibited the decrease in DeltaPsim, downregulated the mRNA expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, and upregulated Bcl-2 mRNA expression. MK-8776 136-143 cyclin dependent kinase 2 Homo sapiens 25-29 28249908-8 2017 Treatment with GSK2334470 or the CDK2 inhibitor dinaciclib was sufficient to reverse these events and to restore the sensitivity of ribociclib-resistant cells to CDK4/6 inhibitors. dinaciclib 48-58 cyclin dependent kinase 2 Homo sapiens 33-37 27515506-9 2017 HSFs treated with GA at non-cytotoxic concentrations (50 to 75muM) significant increased both the S- and G2/M-phase HSFs population, and this event was accompanied with down-regulation of cyclin A, cyclin B, CDK1 and CDK2. Gallic Acid 18-20 cyclin dependent kinase 2 Homo sapiens 217-221 27863047-6 2017 It was observed that although GSK3beta and CDK2 share the conserved ATP-binding pockets, some different residues have significant contributions to protein selectivity. Adenosine Triphosphate 68-71 cyclin dependent kinase 2 Homo sapiens 43-47 28465245-7 2017 Furthermore, 1,25(OH)2D3 stimulated p21 expression and suppressed cyclin-dependent kinase 2 (CDK2) expression in TMK1 in a VDR-dependent manner. Calcitriol 13-24 cyclin dependent kinase 2 Homo sapiens 66-91 28465245-7 2017 Furthermore, 1,25(OH)2D3 stimulated p21 expression and suppressed cyclin-dependent kinase 2 (CDK2) expression in TMK1 in a VDR-dependent manner. Calcitriol 13-24 cyclin dependent kinase 2 Homo sapiens 93-97 28465245-11 2017 SIGNIFICANCE: Our results suggest that 1,25(OH)2D3 inhibits gastric cancer cell growth through VDR and mutp53 interaction followed by the modulation of p21/CDK2. Calcitriol 39-50 cyclin dependent kinase 2 Homo sapiens 156-160 28537766-6 2017 RESULTS: Under proliferative conditions, pirfenidone inhibited Tenon"s fibroblasts proliferation and arrested the cell cycle at the G1 phase; decreased the phosphorylation of AKT, GSK3beta, ERK1/2/MAPK, and JNK/MAPK; increased the phosphorylation of p38 MAPK; and inhibited CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E in a dose-dependent manner. pirfenidone 41-52 cyclin dependent kinase 2 Homo sapiens 274-278 28537766-9 2017 The expression of CDK2, CDK6, cyclin D1, and cyclin D3 were inhibited by LY294002, U0126, and SP600125. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 73-81 cyclin dependent kinase 2 Homo sapiens 18-22 28537766-9 2017 The expression of CDK2, CDK6, cyclin D1, and cyclin D3 were inhibited by LY294002, U0126, and SP600125. U 0126 83-88 cyclin dependent kinase 2 Homo sapiens 18-22 28537766-9 2017 The expression of CDK2, CDK6, cyclin D1, and cyclin D3 were inhibited by LY294002, U0126, and SP600125. pyrazolanthrone 94-102 cyclin dependent kinase 2 Homo sapiens 18-22 28537766-10 2017 SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3beta and MAPK signaling pathways. 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole 0-8 cyclin dependent kinase 2 Homo sapiens 57-61 28537766-10 2017 SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3beta and MAPK signaling pathways. 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole 0-8 cyclin dependent kinase 2 Homo sapiens 199-203 28537766-10 2017 SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3beta and MAPK signaling pathways. pirfenidone 24-35 cyclin dependent kinase 2 Homo sapiens 57-61 28537766-10 2017 SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3beta and MAPK signaling pathways. pirfenidone 24-35 cyclin dependent kinase 2 Homo sapiens 199-203 28537766-10 2017 SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3beta and MAPK signaling pathways. pirfenidone 118-129 cyclin dependent kinase 2 Homo sapiens 199-203 28323486-7 2017 The results suggest that EL inhibits the growth of NSCLC cell lines by downregulating G1-phase cyclins and CDKs, and upregulating p21WAF1/CIP1, which leads to G1-phase cell cycle arrest. 2,3-bis(3'-hydroxybenzyl)butyrolactone 25-27 cyclin dependent kinase 2 Homo sapiens 107-111 28368432-2 2017 Our result shows that the computed binding free energies for five CDK2-ligand complexes using the IE method have a significantly linear correlation with the experimentally measured values with a correlation coefficient of 0.98 in consideration of the bridging water under the PPC force field. Water 260-265 cyclin dependent kinase 2 Homo sapiens 66-70 28412739-7 2017 The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Retinoids 4-13 cyclin dependent kinase 2 Homo sapiens 120-128 28412739-7 2017 The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. tamibarotene 15-19 cyclin dependent kinase 2 Homo sapiens 120-128 28412739-7 2017 The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. tamibarotene 21-33 cyclin dependent kinase 2 Homo sapiens 120-128 28412739-7 2017 The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Tretinoin 49-62 cyclin dependent kinase 2 Homo sapiens 120-128 28368432-0 2017 Effect of electrostatic polarization and bridging water on CDK2-ligand binding affinities calculated using a highly efficient interaction entropy method. Water 50-55 cyclin dependent kinase 2 Homo sapiens 59-63 28368432-1 2017 A new highly efficient interaction entropy (IE) method combined with the polarized protein-specific charge (PPC) force field is employed to investigate the interaction mechanism of CDK2-ligand binding and the effect of the bridging water. Water 232-237 cyclin dependent kinase 2 Homo sapiens 181-185 28024230-2 2017 In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation. pyrazole 116-124 cyclin dependent kinase 2 Homo sapiens 185-210 28128514-0 2017 Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles. Roscovitine 70-81 cyclin dependent kinase 2 Homo sapiens 39-64 28128514-1 2017 The structural basis for the interaction of roscovitine and analogues containing 13 different bioisosteric central heterocycles with the enzyme cyclin-dependent kinase 2 (CDK2) is elucidated. Roscovitine 44-55 cyclin dependent kinase 2 Homo sapiens 144-169 28128514-1 2017 The structural basis for the interaction of roscovitine and analogues containing 13 different bioisosteric central heterocycles with the enzyme cyclin-dependent kinase 2 (CDK2) is elucidated. Roscovitine 44-55 cyclin dependent kinase 2 Homo sapiens 171-175 28128514-4 2017 The interactions of the inhibitors with CDK2 are computationally described by using a hybrid quantum mechanics/semi-empirical quantum mechanics method (QM/SQM), which combines the DFT-D method for the QM part and the PM6-D3H4X method for the SQM part. pm6-d3h4x 217-226 cyclin dependent kinase 2 Homo sapiens 40-44 28024230-0 2017 In silico study of porphyrin-anthraquinone hybrids as CDK2 inhibitor. Porphyrins 19-28 cyclin dependent kinase 2 Homo sapiens 54-58 28024230-0 2017 In silico study of porphyrin-anthraquinone hybrids as CDK2 inhibitor. Anthraquinones 29-42 cyclin dependent kinase 2 Homo sapiens 54-58 28024230-3 2017 The molecular docking simulation revealed that all six porphyrin hybrids were able to bind to ATP-binding site of CDK2 and interacted with key residues constituted the active cavity of CDK2, while molecular dynamics simulation indicated that all porphyrins bound to CDK2 were stable for 6ns. Adenosine Triphosphate 94-97 cyclin dependent kinase 2 Homo sapiens 114-118 28024230-2 2017 In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation. Porphyrins 33-42 cyclin dependent kinase 2 Homo sapiens 185-210 28024230-2 2017 In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation. Porphyrins 33-42 cyclin dependent kinase 2 Homo sapiens 212-216 28024230-2 2017 In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation. Anthraquinones 43-56 cyclin dependent kinase 2 Homo sapiens 185-210 28024230-2 2017 In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation. Anthraquinones 43-56 cyclin dependent kinase 2 Homo sapiens 212-216 28024230-3 2017 The molecular docking simulation revealed that all six porphyrin hybrids were able to bind to ATP-binding site of CDK2 and interacted with key residues constituted the active cavity of CDK2, while molecular dynamics simulation indicated that all porphyrins bound to CDK2 were stable for 6ns. Adenosine Triphosphate 94-97 cyclin dependent kinase 2 Homo sapiens 185-189 28024230-3 2017 The molecular docking simulation revealed that all six porphyrin hybrids were able to bind to ATP-binding site of CDK2 and interacted with key residues constituted the active cavity of CDK2, while molecular dynamics simulation indicated that all porphyrins bound to CDK2 were stable for 6ns. Adenosine Triphosphate 94-97 cyclin dependent kinase 2 Homo sapiens 185-189 28024230-4 2017 The binding free energies predicted by MM-PBSA method showed that most compounds exhibited higher affinity than that of native ligand (4-anilinoquinazoline, DTQ) and the affinity of mono-H2PyP-AQ was about three times better than that of DTQ, indicating its potential to be advanced as a new CDK2 inhibitor. poly(tetramethylene succinate-co-tetramethylene adipate) 42-46 cyclin dependent kinase 2 Homo sapiens 292-296 28024230-4 2017 The binding free energies predicted by MM-PBSA method showed that most compounds exhibited higher affinity than that of native ligand (4-anilinoquinazoline, DTQ) and the affinity of mono-H2PyP-AQ was about three times better than that of DTQ, indicating its potential to be advanced as a new CDK2 inhibitor. anilinoquinazoline 135-155 cyclin dependent kinase 2 Homo sapiens 292-296 28024230-4 2017 The binding free energies predicted by MM-PBSA method showed that most compounds exhibited higher affinity than that of native ligand (4-anilinoquinazoline, DTQ) and the affinity of mono-H2PyP-AQ was about three times better than that of DTQ, indicating its potential to be advanced as a new CDK2 inhibitor. whi-p180 157-160 cyclin dependent kinase 2 Homo sapiens 292-296 28024230-4 2017 The binding free energies predicted by MM-PBSA method showed that most compounds exhibited higher affinity than that of native ligand (4-anilinoquinazoline, DTQ) and the affinity of mono-H2PyP-AQ was about three times better than that of DTQ, indicating its potential to be advanced as a new CDK2 inhibitor. mono-h2pyp-aq 182-195 cyclin dependent kinase 2 Homo sapiens 292-296 28024230-4 2017 The binding free energies predicted by MM-PBSA method showed that most compounds exhibited higher affinity than that of native ligand (4-anilinoquinazoline, DTQ) and the affinity of mono-H2PyP-AQ was about three times better than that of DTQ, indicating its potential to be advanced as a new CDK2 inhibitor. whi-p180 238-241 cyclin dependent kinase 2 Homo sapiens 292-296 28005359-0 2017 Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. 6-substituted 2-arylaminopurines 118-150 cyclin dependent kinase 2 Homo sapiens 97-102 27463516-7 2017 Western blot analysis indicated that PCB77 increased the expression of cyclin E, CDK2, p21, and caspase-9, while PCB40 decreased the expression of these proteins (except CDK2 and p21). 3,4,3',4'-tetrachlorobiphenyl 37-42 cyclin dependent kinase 2 Homo sapiens 81-85 27833088-5 2017 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. 6-alkoxypurines 0-15 cyclin dependent kinase 2 Homo sapiens 74-78 27833088-5 2017 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Adenosine Triphosphate 35-38 cyclin dependent kinase 2 Homo sapiens 74-78 27833088-8 2017 Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 muM; Nek2 IC50 = 0.62 muM) with >10-fold selectivity. 3-((6-(cyclohexylmethoxy)-9h-purin-2-yl)amino)-n,n-dimethylbenzamide 98-166 cyclin dependent kinase 2 Homo sapiens 52-56 27833088-8 2017 Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 muM; Nek2 IC50 = 0.62 muM) with >10-fold selectivity. 3-((6-(cyclohexylmethoxy)-9h-purin-2-yl)amino)-n,n-dimethylbenzamide 98-166 cyclin dependent kinase 2 Homo sapiens 168-172 27833088-10 2017 Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 muM; Nek2 IC50 = 0.27 muM). (e)-dialkylaminovinyl 29-50 cyclin dependent kinase 2 Homo sapiens 165-169 27833088-10 2017 Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 muM; Nek2 IC50 = 0.27 muM). (e)-6-(2-(azepan-1-yl)vinyl)-n-phenyl-9h-purin-2-amine 109-163 cyclin dependent kinase 2 Homo sapiens 165-169 28005359-1 2017 Purines and related heterocycles substituted at C-2 with 4"-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. Purines 0-7 cyclin dependent kinase 2 Homo sapiens 187-191 28005359-2 2017 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Adenosine Triphosphate 56-59 cyclin dependent kinase 2 Homo sapiens 76-80 28005359-2 2017 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Adenosine Triphosphate 56-59 cyclin dependent kinase 2 Homo sapiens 154-158 28005359-3 2017 Most impressive was 4-((6-([1,1"-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 muM) but was ~2000-fold less active toward CDK1 (IC50 86 muM). 4-((6-([1,1"-biphenyl]-3-yl)-9h-purin-2-yl)amino) benzenesulfonamide 20-88 cyclin dependent kinase 2 Homo sapiens 129-133 28005359-5 2017 Crystal structures of inhibitor-kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. Glycine 88-95 cyclin dependent kinase 2 Homo sapiens 186-190 28005359-5 2017 Crystal structures of inhibitor-kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. CID 5045307 135-145 cyclin dependent kinase 2 Homo sapiens 186-190 28107181-4 2017 Because IBC cell lines were highly sensitive to the CDK2 inhibitors dinaciclib and meriolin 5, we developed a high-throughput survival assay (HTSA) to design novel sequential combination strategies based on the presence of cyclin E and CDK2. dinaciclib 68-78 cyclin dependent kinase 2 Homo sapiens 52-56 28181424-1 2017 The first examples of biologically active monocyclic 1,2-azaborines have been synthesized and demonstrated to exhibit not only improved in vitro aqueous solubility in comparison with their corresponding carbonaceous analogues, but in the context of a CDK2 inhibitor, also improved biological activity and better in vivo oral bioavailability. 1,2-azaborine 53-67 cyclin dependent kinase 2 Homo sapiens 251-255 28351316-9 2017 In addition, cyclopentaquinoline derivatives induced expression of cyclin-dependent kinase 2 inhibitor, p21; however, tetrahydroacridine derivatives had no significant effect on p21. Cyclopentaquinoline 13-32 cyclin dependent kinase 2 Homo sapiens 67-92 28107181-4 2017 Because IBC cell lines were highly sensitive to the CDK2 inhibitors dinaciclib and meriolin 5, we developed a high-throughput survival assay (HTSA) to design novel sequential combination strategies based on the presence of cyclin E and CDK2. MERIOLIN 5 83-93 cyclin dependent kinase 2 Homo sapiens 236-240 28980868-2 2017 In this paper, we summarize our recent finding that a novel pathway by which FBW7 loss promotes Centromere Protein A (CENP-A) phosphorylation on Serine 18 through Cyclin E1/CDK2, therefore promoting CIN and tumorigenesis. Serine 145-151 cyclin dependent kinase 2 Homo sapiens 173-177 28101580-12 2017 MeOH fraction arrested HepG2 cells at the G0/G1 phase in a concentration-dependent manner, and resulted in decreased expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, CDK6, p21, and p27. Methanol 0-4 cyclin dependent kinase 2 Homo sapiens 177-182 28101580-14 2017 MeOH fraction treatment also arrested HepG2 cells in the S phase, with decreased expression of cyclin A, CDK2, and CDC25A. Methanol 0-4 cyclin dependent kinase 2 Homo sapiens 105-109 28098804-5 2017 The results showed that olaquindox could induce reactive oxygen species (ROS)-mediated DNA damage and S-phase arrest, where increases of GADD45a, cyclin A, Cdk 2, p21 and p53 protein expression, decrease of cyclin D1 and the activation of phosphorylation-c-Jun N-terminal kinases (p-JNK), phosphorylation-p38 (p-p38) and phosphorylation-extracellular signal-regulated kinases (p-ERK) were involved. olaquindox 24-34 cyclin dependent kinase 2 Homo sapiens 156-161 27888798-5 2017 miR-103 reduced the expression of cyclin dependent kinase (CDK2) and its cyclin E1 target, thereby leading to inhibition of cellular proliferation. mir-103 0-7 cyclin dependent kinase 2 Homo sapiens 59-63 27299463-9 2017 FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. amp-na 66-72 cyclin dependent kinase 2 Homo sapiens 165-169 27299463-10 2017 CONCLUSIONS: Amp-Na exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. amp-na 13-19 cyclin dependent kinase 2 Homo sapiens 143-147 28039837-0 2017 Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines. pyrazolo(1,5-a)pyrimidine 121-147 cyclin dependent kinase 2 Homo sapiens 109-113 28039837-2 2017 To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. pyrazolo(1,5-a)pyrimidine 88-113 cyclin dependent kinase 2 Homo sapiens 46-71 28039837-2 2017 To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. pyrazolo(1,5-a)pyrimidine 88-113 cyclin dependent kinase 2 Homo sapiens 73-77 28039837-3 2017 The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. pyrazolo(1,5-a)pyrimidine 146-171 cyclin dependent kinase 2 Homo sapiens 64-68 28039837-3 2017 The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. Water 240-245 cyclin dependent kinase 2 Homo sapiens 64-68 26478521-7 2017 RESULTS: DHTI treatment inhibited the proliferation of 143B cells in a dose- and time-dependent manner through arresting cells in G1 phase by reducing the expression of cyclin D1, cyclin E1, CDK2, CDK4, CDK6, p-Rb, E2F1, SKP2 and increasing the expression of P53, P21cip1, P27kip1. dhts 9-13 cyclin dependent kinase 2 Homo sapiens 191-195 28785594-8 2017 Moreover, pterostilbene treatment markedly induced S-phase cell cycle arrest, which was accompanied by downregulation of cdc25A, cyclin A2, and CDK2. pterostilbene 10-23 cyclin dependent kinase 2 Homo sapiens 144-148 29055954-9 2017 Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of beta-catenin, cyclin A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however, artesunate had no impact on CDK2 expression in MG-63 cells. Artesunate 58-68 cyclin dependent kinase 2 Homo sapiens 232-236 27774879-9 2017 In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR). nardostachysin 68-82 cyclin dependent kinase 2 Homo sapiens 240-265 29131001-7 2017 We demonstrated that atorvastatin calcium induced cell cycle arrest in the G0/G1 phase in response to PDGF-betabeta stimulation and decreased the expression of G0/G1-specific regulatory proteins, including proliferating cell nuclear antigen (PCNA), CDK2, cyclin D1, cyclin E and CDK4 in PDGF-betabeta-treated VSMCs. Atorvastatin 21-41 cyclin dependent kinase 2 Homo sapiens 249-253 27774879-9 2017 In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR). nardostachysin 68-82 cyclin dependent kinase 2 Homo sapiens 267-271 27774879-9 2017 In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR). nardosinone 102-113 cyclin dependent kinase 2 Homo sapiens 240-265 26678675-5 2017 PEITC may induce G0/G1 cell-cycle arrest through affecting the proteins such as cdk2, cyclin E, and p21 in GBM 8401 cells. phenethyl isothiocyanate 0-5 cyclin dependent kinase 2 Homo sapiens 80-84 27774879-9 2017 In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR). nardosinone 102-113 cyclin dependent kinase 2 Homo sapiens 267-271 27657825-10 2016 Curcumin induced G0/G1 arrest in DU-145 cells, and G0/G1 phase related regulatory factors Cyclin D1 and CDK2 expressions were inhibited. Curcumin 0-8 cyclin dependent kinase 2 Homo sapiens 104-108 27960113-4 2017 Our results demonstrate that tebufenozide could trigger arrest in G1/S phase related to a downregulation of cyclin E and cyclin-dependent kinase (CDK) 2 protein. tebufenozide 29-41 cyclin dependent kinase 2 Homo sapiens 121-152 27977759-3 2016 Viscolin reduced the PDGF-BB-induced HASMC proliferation and migration in vitro; it also arrested HASMCs in the G0/G1 phase by decreasing the protein expression of Cyclin D1, CDK2, Cyclin E, CDK4, and p21Cip1 as detected by Western blot analysis. viscolin 0-8 cyclin dependent kinase 2 Homo sapiens 175-179 28024406-2 2016 Conformational flexibility of the ATP-binding site in the CDK2 and ERK2 kinases was identified using molecular dynamics simulations. Adenosine Triphosphate 34-37 cyclin dependent kinase 2 Homo sapiens 58-62 27815502-3 2016 We and others have reported that human SAMHD1 interacts with the cell cycle regulatory proteins cyclin A, CDK1, and CDK2, which mediates phosphorylation of SAMHD1 at threonine 592, a post-translational modification that has been implicated in abrogating SAMHD1 restriction function and ability to form stable tetramers. Threonine 166-175 cyclin dependent kinase 2 Homo sapiens 116-120 27922047-6 2016 In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. benzo(h)quinoline 45-63 cyclin dependent kinase 2 Homo sapiens 157-161 27898692-0 2016 Targeting CDKs with Roscovitine Increases Sensitivity to DNA Damaging Drugs of Human Osteosarcoma Cells. Roscovitine 20-31 cyclin dependent kinase 2 Homo sapiens 10-14 27748837-6 2016 This study demonstrated that EMMQ induced DNA damage by activating p53 and gamma-H2AX and cell arrest by suppressing cyclin D1 and CDK2. 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline 29-33 cyclin dependent kinase 2 Homo sapiens 131-135 27779703-6 2016 In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl-2 protein expression. Resveratrol 13-24 cyclin dependent kinase 2 Homo sapiens 204-208 27898692-3 2016 We also assessed the in vitro efficacy of the CDKs inhibitor roscovitine in a panel of drug-sensitive and drug-resistant human OS cell lines. Roscovitine 61-72 cyclin dependent kinase 2 Homo sapiens 46-50 27898692-6 2016 These findings indicated CDK2 as a promising candidate therapeutic marker for OS and therefore we assessed the efficacy of the CDKs-inhibitor roscovitine in both drug-sensitive and -resistant OS cell lines. Roscovitine 142-153 cyclin dependent kinase 2 Homo sapiens 127-131 27904776-5 2016 Then cell viability, cell cycle and the expressions of CyclinB1, CyclinD1 and Cyclin-Dependent Kinase 2 (CDK2) were respectively detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, qPCR and Western blot. monooxyethylene trimethylolpropane tristearate 205-208 cyclin dependent kinase 2 Homo sapiens 78-103 27412172-7 2016 MG treatment also downregulated factors that are upstream of RB-E2F1 signaling such as Cdk2, Cyclin E, Cdk4, and Cyclin D1 where Cyclin D3 level was unaffected. methyl gallate 0-2 cyclin dependent kinase 2 Homo sapiens 87-91 27904776-5 2016 Then cell viability, cell cycle and the expressions of CyclinB1, CyclinD1 and Cyclin-Dependent Kinase 2 (CDK2) were respectively detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, qPCR and Western blot. monooxyethylene trimethylolpropane tristearate 205-208 cyclin dependent kinase 2 Homo sapiens 105-109 28009971-11 2016 Cdk1 and Cdk2 protein levels declined after dacomitinib treatment; epithelial-mesenchymal transition (EMT) was inhibited, which was confirmed by observing E-cadherin, N-cadherin, and slug inhibition. dacomitinib 44-55 cyclin dependent kinase 2 Homo sapiens 9-13 27726305-6 2016 Solanine regulates the protein levels of cell cycle proteins, including Cyclin D1, Cyclin E1, CDK2, CDK4, CDK6, and P21 in vivo and in vitro. Solanine 0-8 cyclin dependent kinase 2 Homo sapiens 94-98 27550941-8 2016 Overexpression of CP110, which is a mediator of CDK2 inhibitor-induced anaphase catastrophe (and a CDK1 and 2 phosphorylation substrate), antagonized anaphase catastrophe and apoptosis following dinaciclib treatment. dinaciclib 195-205 cyclin dependent kinase 2 Homo sapiens 48-52 27849335-5 2016 VC-A strongly inhibited the proliferation and induced cell cycle arrest in G2/M phase associated with the inhibition of cell cycle regulatory proteins cyclin D, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4, cdk6 and cdk inhibitors WAF1/21 and KIP1/27. muconomycin A 0-4 cyclin dependent kinase 2 Homo sapiens 197-201 27849335-5 2016 VC-A strongly inhibited the proliferation and induced cell cycle arrest in G2/M phase associated with the inhibition of cell cycle regulatory proteins cyclin D, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4, cdk6 and cdk inhibitors WAF1/21 and KIP1/27. muconomycin A 0-4 cyclin dependent kinase 2 Homo sapiens 203-207 27477352-9 2016 In addition, radotinib induced G0/G1 phase arrest by inducing CDKIs p21 and p27 and by inhibiting CDK2, CDK4, and CDK6. 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide 13-22 cyclin dependent kinase 2 Homo sapiens 98-102 29137354-3 2017 Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression. dinaciclib 314-324 cyclin dependent kinase 2 Homo sapiens 219-223 29137354-3 2017 Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression. palbociclib 357-368 cyclin dependent kinase 2 Homo sapiens 219-223 29137354-4 2017 We then expressed the ER-activating mutations ERmut(Y537S) and ERmut(D538G) in MCF7 cells, and demonstrated their ability to induce ligand-independent and tamoxifen-resistant growth, associated with constitutive and CDK2-dependent pS294 expression. Tamoxifen 155-164 cyclin dependent kinase 2 Homo sapiens 216-220 27424288-4 2016 Our results suggested that NJXA induced G0/G1 cell cycle arrest in HeLa and SiHa cells by down-regulating cyclins B1, E1, and A and cyclin-dependent kinases 2, 4 and 6, while selectively restoring p27. nujiangexathone A 27-31 cyclin dependent kinase 2 Homo sapiens 106-167 27698449-8 2016 We found p53 could inhibit pro-survival genes B-cell lymphoma-2 (Bcl-2), myeloid leukemia-1 (Mcl-1) and S phase related cell cycle proteins cyclin-dependent kinase 2 (CDK2), Cyclin E to induce premature senescence, and the functional role of ROS in Cr(VI)-induced premature senescence is depend on p53. Reactive Oxygen Species 242-245 cyclin dependent kinase 2 Homo sapiens 167-171 27541047-3 2016 In vitro, at low concentration (<250nM) of Chidamide inhibited cell proliferation and delayed G0/G1 cell cycle progression by down-regulating CDK2 and regulating p-P53 and P21 protein expression. N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide 46-55 cyclin dependent kinase 2 Homo sapiens 145-149 27698776-7 2016 Cucurbitacin B treatment significantly suppressed the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4 (CDK4) and CDK2, while increasing the expression of p27. cucurbitacin B 0-14 cyclin dependent kinase 2 Homo sapiens 126-130 27297568-0 2016 Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy. benzamide 0-9 cyclin dependent kinase 2 Homo sapiens 70-74 27654866-9 2016 Furthermore, western blot showed that bicyclol inhibited phosphorylation of Akt and ERK, down-regulated the expressions of cyclin D1, cyclin E2, CDK2, CDK4, p-Rb and p-mTOR. bicyclol 38-46 cyclin dependent kinase 2 Homo sapiens 145-149 27626431-9 2016 Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex. r-pe 11-15 cyclin dependent kinase 2 Homo sapiens 170-174 27626431-9 2016 Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex. r-pe 11-15 cyclin dependent kinase 2 Homo sapiens 170-173 27608612-11 2016 It was apparent that HP upregulates miR-3180-5p, which inhibits the expression of PODN and promotes HBSMC proliferation via the cdk2 signaling pathway. histidylproline 21-23 cyclin dependent kinase 2 Homo sapiens 128-132 27432244-5 2016 Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin 0-8 cyclin dependent kinase 2 Homo sapiens 113-118 27525951-2 2016 Therefore, target fishing of glycopentalone using a combined approach of inverse docking and reverse pharmacophore mapping approach was used to identify potential targets of glycopentalone, and gain insight into its binding modes against the selected molecular targets, viz., CDK-2, CDK-6, Topoisomerase I, Bcl-2, VEGFR-2, Telomere:G-quadruplex and Topoisomerase II. 1-(2-hydroxy-3- methyl 4,5-dimethoxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one 29-43 cyclin dependent kinase 2 Homo sapiens 276-281 27525951-2 2016 Therefore, target fishing of glycopentalone using a combined approach of inverse docking and reverse pharmacophore mapping approach was used to identify potential targets of glycopentalone, and gain insight into its binding modes against the selected molecular targets, viz., CDK-2, CDK-6, Topoisomerase I, Bcl-2, VEGFR-2, Telomere:G-quadruplex and Topoisomerase II. 1-(2-hydroxy-3- methyl 4,5-dimethoxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one 174-188 cyclin dependent kinase 2 Homo sapiens 276-281 27525951-5 2016 Further, the binding affinities of glycopentalone to the targets were in the order: Telomere:G-quadruplex > VEGFR-2 > CDK-6 > CDK-2 > Topoisomerase II > Topoisomerase I > Bcl-2. 1-(2-hydroxy-3- methyl 4,5-dimethoxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one 35-49 cyclin dependent kinase 2 Homo sapiens 135-140 27525951-7 2016 The targets were validated by reverse pharmacophore mapping of glycopentalone against a set of 2241 known human target proteins which revealed CDK-2 and VEGFR-2 as the most favorable targets. 1-(2-hydroxy-3- methyl 4,5-dimethoxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one 63-77 cyclin dependent kinase 2 Homo sapiens 143-148 27525951-8 2016 The glycopentalone was well mapped to CDK-2 and VEGFR-2 which involve six pharmacophore features (two hydrophobic centers and four hydrogen bond acceptors) and nine pharmacophore features (five hydrophobic, two hydrogen bond acceptors and two hydrogen bond donors), respectively. 1-(2-hydroxy-3- methyl 4,5-dimethoxyphenyl)-3-(1H-pyrrol-2-yl)-2-propen-1-one 4-18 cyclin dependent kinase 2 Homo sapiens 38-43 27525951-8 2016 The glycopentalone was well mapped to CDK-2 and VEGFR-2 which involve six pharmacophore features (two hydrophobic centers and four hydrogen bond acceptors) and nine pharmacophore features (five hydrophobic, two hydrogen bond acceptors and two hydrogen bond donors), respectively. Hydrogen 131-139 cyclin dependent kinase 2 Homo sapiens 38-43 27525951-8 2016 The glycopentalone was well mapped to CDK-2 and VEGFR-2 which involve six pharmacophore features (two hydrophobic centers and four hydrogen bond acceptors) and nine pharmacophore features (five hydrophobic, two hydrogen bond acceptors and two hydrogen bond donors), respectively. Hydrogen 211-219 cyclin dependent kinase 2 Homo sapiens 38-43 27525951-8 2016 The glycopentalone was well mapped to CDK-2 and VEGFR-2 which involve six pharmacophore features (two hydrophobic centers and four hydrogen bond acceptors) and nine pharmacophore features (five hydrophobic, two hydrogen bond acceptors and two hydrogen bond donors), respectively. Hydrogen 211-219 cyclin dependent kinase 2 Homo sapiens 38-43 27657032-3 2016 Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Adenosine Triphosphate 46-49 cyclin dependent kinase 2 Homo sapiens 41-45 27657032-3 2016 Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Adenosine Triphosphate 46-49 cyclin dependent kinase 2 Homo sapiens 74-78 27657032-3 2016 Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Adenosine Triphosphate 46-49 cyclin dependent kinase 2 Homo sapiens 74-78 27657032-8 2016 In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Adenosine Triphosphate 88-91 cyclin dependent kinase 2 Homo sapiens 83-87 27657032-12 2016 Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors. Alprostadil 0-16 cyclin dependent kinase 2 Homo sapiens 72-76 27657032-12 2016 Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors. Masoprocol 21-25 cyclin dependent kinase 2 Homo sapiens 72-76 27622654-0 2016 A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516. SU 9516 139-145 cyclin dependent kinase 2 Homo sapiens 124-128 27622654-15 2016 SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor, which we showed also had an EMT-inhibitory activity. SU 9516 0-6 cyclin dependent kinase 2 Homo sapiens 13-38 27622654-15 2016 SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor, which we showed also had an EMT-inhibitory activity. SU 9516 0-6 cyclin dependent kinase 2 Homo sapiens 40-44 27529512-3 2016 METHODS: We have synthesised and characterised a series of 6-aminopyrimidines identified from a kinase screen that inhibit PI3K and/or mTOR and/or CDK2. 4-aminopyrimidine 59-77 cyclin dependent kinase 2 Homo sapiens 147-151 27529512-8 2016 Combination of NU6102 (CDK2 inhibitor) and pictilisib (GDC-0941; pan-PI3K inhibitor) resulted in synergistic growth inhibition, and enhanced cytotoxicity in HT29 cells in vitro and HT29 tumour growth inhibition in vivo. NU6102 15-21 cyclin dependent kinase 2 Homo sapiens 23-27 27573873-8 2016 The blocking of cell cycle progression by VC-A was associated with the inhibition of cell cycle regulatory proteins cyclin D1, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4 and cdk inhibitor WAF1/21. muconomycin A 42-46 cyclin dependent kinase 2 Homo sapiens 163-167 27573873-8 2016 The blocking of cell cycle progression by VC-A was associated with the inhibition of cell cycle regulatory proteins cyclin D1, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4 and cdk inhibitor WAF1/21. muconomycin A 42-46 cyclin dependent kinase 2 Homo sapiens 169-173 27355194-0 2016 Synthesis and Biological Evaluation of N(2) -Substituted 2,4-Diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines and Related 5-Cyano-NNO-azoxy Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors. n(2) -substituted 2,4-diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines 39-109 cyclin dependent kinase 2 Homo sapiens 155-180 27355194-0 2016 Synthesis and Biological Evaluation of N(2) -Substituted 2,4-Diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines and Related 5-Cyano-NNO-azoxy Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors. n(2) -substituted 2,4-diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines 39-109 cyclin dependent kinase 2 Homo sapiens 182-186 27355194-0 2016 Synthesis and Biological Evaluation of N(2) -Substituted 2,4-Diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines and Related 5-Cyano-NNO-azoxy Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors. 5-cyano-nno-azoxy derivatives 122-151 cyclin dependent kinase 2 Homo sapiens 155-180 27355194-0 2016 Synthesis and Biological Evaluation of N(2) -Substituted 2,4-Diamino-6-cyclohexylmethoxy-5-nitrosopyrimidines and Related 5-Cyano-NNO-azoxy Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors. 5-cyano-nno-azoxy derivatives 122-151 cyclin dependent kinase 2 Homo sapiens 182-186 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 68-74 cyclin dependent kinase 2 Homo sapiens 25-50 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 68-74 cyclin dependent kinase 2 Homo sapiens 52-56 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 68-74 cyclin dependent kinase 2 Homo sapiens 297-301 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine 76-127 cyclin dependent kinase 2 Homo sapiens 25-50 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine 76-127 cyclin dependent kinase 2 Homo sapiens 52-56 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine 76-127 cyclin dependent kinase 2 Homo sapiens 297-301 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 2,4-diaminopyrimidine 106-127 cyclin dependent kinase 2 Homo sapiens 25-50 27355194-1 2016 The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6-cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 2,4-diaminopyrimidine 106-127 cyclin dependent kinase 2 Homo sapiens 52-56 27355194-4 2016 Substitution of the 5-nitroso group with a 5-cyano-NNO-azoxy moiety afforded a new class of inhibitors, the activity of which against CDK2 was found to be similar to that of the nitroso series. 5-nitroso 20-29 cyclin dependent kinase 2 Homo sapiens 134-138 27355194-4 2016 Substitution of the 5-nitroso group with a 5-cyano-NNO-azoxy moiety afforded a new class of inhibitors, the activity of which against CDK2 was found to be similar to that of the nitroso series. 5-cyano-nno-azoxy 43-60 cyclin dependent kinase 2 Homo sapiens 134-138 27355194-6 2016 Taken together, these new analogues of NU6027 enhance our understanding of the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 39-45 cyclin dependent kinase 2 Homo sapiens 138-142 27355194-6 2016 Taken together, these new analogues of NU6027 enhance our understanding of the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. 2,4-diaminopyrimidine 116-137 cyclin dependent kinase 2 Homo sapiens 138-142 27297568-0 2016 Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy. Adenosine Triphosphate 40-43 cyclin dependent kinase 2 Homo sapiens 70-74 27307074-6 2016 Disrupting CDK2 activity is able to induce sustained DNA damage, as demonstrated by the formation of distinct gammaH2AX foci in nuclei of Day-3 and Day-5 embryos. gammah2ax 110-119 cyclin dependent kinase 2 Homo sapiens 11-15 27233942-5 2016 Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2( -) and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. Reactive Oxygen Species 66-69 cyclin dependent kinase 2 Homo sapiens 234-238 27233942-5 2016 Stronger intracellular TrxR inhibition and higher accumulation of ROS (O2( -) and H2O2) are responsible for more effective S-phase arrest and mitochondria-mediated apoptotic induction of A549 cells by PL-CL than PLvia p53-p21-cyclinA/CDK2 and ASK1-JNK/p38 signaling cascade pathways, respectively. pl-cl 201-206 cyclin dependent kinase 2 Homo sapiens 234-238 27350339-5 2016 High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Glucose 5-12 cyclin dependent kinase 2 Homo sapiens 143-147 27378523-0 2016 Multiple CDK inhibitor dinaciclib suppresses neuroblastoma growth via inhibiting CDK2 and CDK9 activity. dinaciclib 23-33 cyclin dependent kinase 2 Homo sapiens 81-85 27378523-4 2016 Here we show that a novel multiple-CDK inhibitor, dinaciclib (SCH727965, MK-7965), exhibits potent anti-proliferative effects on a panel of NB cell lines by blocking the activity of CDK2 and CDK9. dinaciclib 50-60 cyclin dependent kinase 2 Homo sapiens 182-186 27378523-4 2016 Here we show that a novel multiple-CDK inhibitor, dinaciclib (SCH727965, MK-7965), exhibits potent anti-proliferative effects on a panel of NB cell lines by blocking the activity of CDK2 and CDK9. dinaciclib 62-71 cyclin dependent kinase 2 Homo sapiens 182-186 27378523-4 2016 Here we show that a novel multiple-CDK inhibitor, dinaciclib (SCH727965, MK-7965), exhibits potent anti-proliferative effects on a panel of NB cell lines by blocking the activity of CDK2 and CDK9. dinaciclib 73-80 cyclin dependent kinase 2 Homo sapiens 182-186 27447597-0 2016 Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27(KIP1)-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells. protocatechualdehyde 0-20 cyclin dependent kinase 2 Homo sapiens 99-103 27259234-0 2016 A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway. arylbenzofuran 8-22 cyclin dependent kinase 2 Homo sapiens 99-103 27259234-5 2016 Knockdown of cyclin A2 using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced G1/S-phase arrest. alvocidib 94-106 cyclin dependent kinase 2 Homo sapiens 75-79 27231022-9 2016 Western blot analysis indicated that vitamin C treatment up-regulated the expression levels of cyclin E1 and CDK2, but down-regulated p53 and p21 proteins expression, which contributed to cell proliferation and cell cycle progression. Ascorbic Acid 37-46 cyclin dependent kinase 2 Homo sapiens 109-113 28911558-4 2016 Western blotting assay indicated that ZTP induced cell-cycle arrest by upregulation of p53 and reduced the expression of CDK2 in MCF-7 cells. ztp 38-41 cyclin dependent kinase 2 Homo sapiens 121-125 27269920-5 2016 After the treatment with cdk2 inhibitor (Purvalanol A), the expression levels of relevant proteins in NCI-N87/TR cells were detected by Western blot, and the sensitivity to trastuzumab was analyzed by MTT assay. 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine 41-53 cyclin dependent kinase 2 Homo sapiens 25-29 26104856-5 2016 Wogonoside promotes the expression of GATA-1 and facilitates the binding to methyl ethyl ketone (MEK) and p21 promoter, thus inhibiting MEK/extracellular signal-regulated kinase signaling and cell cycle checkpoint proteins, including CDK2, CDK4, cyclin A, and cyclin D1, and increasing p21 expression. wogonoside 0-10 cyclin dependent kinase 2 Homo sapiens 234-238 26983952-5 2016 Phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE. Phloretin 0-9 cyclin dependent kinase 2 Homo sapiens 112-116 26988343-2 2016 Here, we identified, for the first time, the phosphorylation of serine 687 (Ser(687)), which is located in the highly conserved nuclear localization signal (NLS) region of human poleta and is mediated by cyclin-dependent kinase 2 (CDK2). Serine 64-70 cyclin dependent kinase 2 Homo sapiens 204-229 26988343-2 2016 Here, we identified, for the first time, the phosphorylation of serine 687 (Ser(687)), which is located in the highly conserved nuclear localization signal (NLS) region of human poleta and is mediated by cyclin-dependent kinase 2 (CDK2). Serine 64-70 cyclin dependent kinase 2 Homo sapiens 231-235 26988343-2 2016 Here, we identified, for the first time, the phosphorylation of serine 687 (Ser(687)), which is located in the highly conserved nuclear localization signal (NLS) region of human poleta and is mediated by cyclin-dependent kinase 2 (CDK2). Serine 76-79 cyclin dependent kinase 2 Homo sapiens 204-229 26988343-2 2016 Here, we identified, for the first time, the phosphorylation of serine 687 (Ser(687)), which is located in the highly conserved nuclear localization signal (NLS) region of human poleta and is mediated by cyclin-dependent kinase 2 (CDK2). Serine 76-79 cyclin dependent kinase 2 Homo sapiens 231-235 27211815-6 2016 Interestingly, the unfolding of p27 leaves CDK2/CyclinA in an active state, where the prerequisite CDK2-CyclinA interfacial contacts were regained and ATP achieved its native position for smooth transfer of phosphate. Adenosine Triphosphate 151-154 cyclin dependent kinase 2 Homo sapiens 43-47 27211815-6 2016 Interestingly, the unfolding of p27 leaves CDK2/CyclinA in an active state, where the prerequisite CDK2-CyclinA interfacial contacts were regained and ATP achieved its native position for smooth transfer of phosphate. Phosphates 207-216 cyclin dependent kinase 2 Homo sapiens 43-47 27074557-3 2016 In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. honokiol 56-60 cyclin dependent kinase 2 Homo sapiens 90-132 27074557-3 2016 In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. magnolol 65-68 cyclin dependent kinase 2 Homo sapiens 90-132 27074557-3 2016 In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. hono-mag 70-78 cyclin dependent kinase 2 Homo sapiens 90-132 27090615-0 2016 Conformational Adaption May Explain the Slow Dissociation Kinetics of Roniciclib (BAY 1000394), a Type I CDK Inhibitor with Kinetic Selectivity for CDK2 and CDK9. roniciclib 70-80 cyclin dependent kinase 2 Homo sapiens 148-152 27090615-0 2016 Conformational Adaption May Explain the Slow Dissociation Kinetics of Roniciclib (BAY 1000394), a Type I CDK Inhibitor with Kinetic Selectivity for CDK2 and CDK9. roniciclib 82-93 cyclin dependent kinase 2 Homo sapiens 148-152 27090615-2 2016 Here, we show that roniciclib displays prolonged residence times on CDK2 and CDK9, whereas residence times on other CDKs are transient, thus giving rise to a kinetic selectivity of roniciclib. roniciclib 19-29 cyclin dependent kinase 2 Homo sapiens 68-72 27090615-2 2016 Here, we show that roniciclib displays prolonged residence times on CDK2 and CDK9, whereas residence times on other CDKs are transient, thus giving rise to a kinetic selectivity of roniciclib. roniciclib 181-191 cyclin dependent kinase 2 Homo sapiens 116-120 27090615-4 2016 CDK2 X-ray cocrystal structures have revealed a DFG-loop adaption for the 5-(trifluoromethyl) substituent, while for hydrogen and bromo substituents the DFG loop remains in its characteristic type I inhibitor position. 1,3-Diphenylguanidine 48-51 cyclin dependent kinase 2 Homo sapiens 0-4 27090615-4 2016 CDK2 X-ray cocrystal structures have revealed a DFG-loop adaption for the 5-(trifluoromethyl) substituent, while for hydrogen and bromo substituents the DFG loop remains in its characteristic type I inhibitor position. Hydrogen 117-125 cyclin dependent kinase 2 Homo sapiens 0-4 27090615-4 2016 CDK2 X-ray cocrystal structures have revealed a DFG-loop adaption for the 5-(trifluoromethyl) substituent, while for hydrogen and bromo substituents the DFG loop remains in its characteristic type I inhibitor position. 1,3-Diphenylguanidine 153-156 cyclin dependent kinase 2 Homo sapiens 0-4 27090615-5 2016 In tumor cells, the prolonged residence times of roniciclib on CDK2 and CDK9 are reflected in a sustained inhibitory effect on retinoblastoma protein (RB) phosphorylation, indicating that the target residence time on CDK2 may contribute to sustained target engagement and antitumor efficacy. roniciclib 49-59 cyclin dependent kinase 2 Homo sapiens 63-67 27090615-5 2016 In tumor cells, the prolonged residence times of roniciclib on CDK2 and CDK9 are reflected in a sustained inhibitory effect on retinoblastoma protein (RB) phosphorylation, indicating that the target residence time on CDK2 may contribute to sustained target engagement and antitumor efficacy. roniciclib 49-59 cyclin dependent kinase 2 Homo sapiens 217-221 26387543-2 2016 This interaction is abrogated by cyclin A-CDK2-mediated phosphorylation of BRCA2 at serine 3291 (Ser3291). Serine 84-90 cyclin dependent kinase 2 Homo sapiens 42-46 27223122-8 2016 Furthermore, APY606 treatment directly inhibited Ras-GTP and the downstream activation of MAPK, which resulted in the down-regulation of anti-apoptotic protein Bcl-2, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, cytosolic Cytochrome c and Caspase 3) and of cyclin-dependent kinase 2 and Cyclin A, E. These data suggest that impairing Ras-MAPK signaling is a novel mechanism of action for APY606 during therapeutic intervention in pancreatic cancer. apy606 13-19 cyclin dependent kinase 2 Homo sapiens 299-324 27269920-7 2016 Restoration of the p27kip1 protein expression by cdk2 inhibitor (Purvalanol A) increased the sensitivity of NCI-N87/TR to trastuzumab. 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine 65-77 cyclin dependent kinase 2 Homo sapiens 49-53 27100206-10 2016 CDK2 was simulated in the apo-form and in complex with the allosteric inhibitor 8-anilino-1-napthalenesulfonic acid (ANS). 8-anilino-1-napthalenesulfonic acid 80-115 cyclin dependent kinase 2 Homo sapiens 0-4 27100206-10 2016 CDK2 was simulated in the apo-form and in complex with the allosteric inhibitor 8-anilino-1-napthalenesulfonic acid (ANS). 1-anilino-8-naphthalenesulfonate 117-120 cyclin dependent kinase 2 Homo sapiens 0-4 27100206-13 2016 In contrast, the CDK2/ANS complex landscape is compatible with a conformational selection picture where the binding of ANS in proximity of the alphaC helix causes a population shift toward the inactive conformation. 1-anilino-8-naphthalenesulfonate 22-25 cyclin dependent kinase 2 Homo sapiens 17-21 27100206-13 2016 In contrast, the CDK2/ANS complex landscape is compatible with a conformational selection picture where the binding of ANS in proximity of the alphaC helix causes a population shift toward the inactive conformation. 1-anilino-8-naphthalenesulfonate 119-122 cyclin dependent kinase 2 Homo sapiens 17-21 26851505-2 2016 The most potent compounds contained various hydroxyalkylamines at the 5 position and possessed low nanomolar IC50 values for CDK2 and CDK5. hydroxyalkylamines 44-62 cyclin dependent kinase 2 Homo sapiens 125-129 26714749-6 2016 Furthermore, proteosomal inhibitor MG132 treatment rescued the downregulation of CDK2 in SATB2-silenced SKOV3 cells. benzyloxycarbonylleucyl-leucyl-leucine aldehyde 35-40 cyclin dependent kinase 2 Homo sapiens 81-85 26883408-0 2016 Molecular modeling studies to characterize N-phenylpyrimidin-2-amine selectivity for CDK2 and CDK4 through 3D-QSAR and molecular dynamics simulations. N-phenylpyrimidin-2-amine 43-68 cyclin dependent kinase 2 Homo sapiens 85-89 26883408-3 2016 In this study, 4-substituted N-phenylpyrimidin-2-amine derivatives as CDK2 inhibitors were examined to understand the selectivity mechanism against CDK4 using a combined approach of 3D-QSAR, molecular docking, MESP, MD simulations, and binding free energy calculations. 4-substituted n-phenylpyrimidin-2-amine 15-54 cyclin dependent kinase 2 Homo sapiens 70-74 26910110-0 2016 Covalent Modification of CDK2 by 4-Hydroxynonenal as a Mechanism of Inhibition of Cell Cycle Progression. 4-hydroxy-2-nonenal 33-49 cyclin dependent kinase 2 Homo sapiens 25-29 27051274-7 2016 AZD1080 also significantly downregulated GSK-3beta, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels. 2-hydroxy-3-(5-((morpholin-4-yl)methyl)pyridin-2-yl)-1H-indole-5-carbonitrile 0-7 cyclin dependent kinase 2 Homo sapiens 52-56 26709138-8 2016 Similarly, Western blot results indicate that aPPD significantly upregulated Vitamin D receptor (VDR) expression, while calcitriol further enhanced the ability of aPPD to induce pro-apoptotic BAX, increased cleaved caspase-3 and downregulate cdk2 protein levels. Calcitriol 120-130 cyclin dependent kinase 2 Homo sapiens 242-246 27087371-5 2016 The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up-regulated in the MGC-803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. jaridonin 110-119 cyclin dependent kinase 2 Homo sapiens 60-64 27087371-5 2016 The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up-regulated in the MGC-803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. jaridonin 110-119 cyclin dependent kinase 2 Homo sapiens 160-164 26849940-4 2016 Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. dioscin 36-43 cyclin dependent kinase 2 Homo sapiens 96-121 26849940-4 2016 Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. dioscin 36-43 cyclin dependent kinase 2 Homo sapiens 123-127 26518266-7 2016 A complex sequence of enzymatic events, including phosphorylation by CDK2, PARylation by PARP1 and the ATP-dependent activity of NURF, are required for H1 displacement and gene de-repression, as a prerequisite for further nucleosome remodeling. Adenosine Triphosphate 103-106 cyclin dependent kinase 2 Homo sapiens 69-73 26871934-0 2016 Scaffold Hopping Approach to a New Series of Pyridine Derivatives as Potent Inhibitors of CDK2. pyridine 45-53 cyclin dependent kinase 2 Homo sapiens 90-94 26871934-1 2016 A scaffold hopping approach was exploited to guide the discovery of a series of pyridine derivatives as novel cyclin-dependent kinase (CDK2) inhibitors. pyridine 80-88 cyclin dependent kinase 2 Homo sapiens 135-139 26796279-9 2016 The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 19-27 cyclin dependent kinase 2 Homo sapiens 104-108 26685215-0 2016 Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention. Aspirin 39-46 cyclin dependent kinase 2 Homo sapiens 14-18 26685215-0 2016 Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention. Salicylic Acid 51-65 cyclin dependent kinase 2 Homo sapiens 14-18 26685215-2 2016 We hypothesized that aspirin"s chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin-dependent kinase-2 (CDK2). Aspirin 21-28 cyclin dependent kinase 2 Homo sapiens 174-178 26685215-3 2016 In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. Aspirin 96-103 cyclin dependent kinase 2 Homo sapiens 180-184 26685215-3 2016 In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. Salicylic Acid 132-146 cyclin dependent kinase 2 Homo sapiens 180-184 26685215-5 2016 In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Salicylic Acid 67-81 cyclin dependent kinase 2 Homo sapiens 102-106 26685215-6 2016 Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Salicylic Acid 57-71 cyclin dependent kinase 2 Homo sapiens 90-94 26685215-7 2016 First, inclusion of salicylic acid in naive cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Salicylic Acid 20-34 cyclin dependent kinase 2 Homo sapiens 129-133 26685215-7 2016 First, inclusion of salicylic acid in naive cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Salicylic Acid 20-34 cyclin dependent kinase 2 Homo sapiens 129-133 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. 8-anilino-1-naphthalenesulfonic acid 11-44 cyclin dependent kinase 2 Homo sapiens 51-55 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. 8-anilino-1-naphthalenesulfonic acid 11-44 cyclin dependent kinase 2 Homo sapiens 94-98 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. 8-anilino-1-naphthalenesulfonic acid 46-49 cyclin dependent kinase 2 Homo sapiens 51-55 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. 8-anilino-1-naphthalenesulfonic acid 46-49 cyclin dependent kinase 2 Homo sapiens 94-98 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Salicylic Acid 104-118 cyclin dependent kinase 2 Homo sapiens 51-55 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Salicylic Acid 104-118 cyclin dependent kinase 2 Homo sapiens 94-98 26685215-8 2016 Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. 8-anilino-1-naphthalenesulfonic acid 169-172 cyclin dependent kinase 2 Homo sapiens 94-98 26685215-9 2016 Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. Salicylic Acid 116-130 cyclin dependent kinase 2 Homo sapiens 149-153 26685215-10 2016 These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Aspirin 31-38 cyclin dependent kinase 2 Homo sapiens 81-85 26685215-10 2016 These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Salicylic Acid 43-57 cyclin dependent kinase 2 Homo sapiens 81-85 26685215-11 2016 IMPLICATIONS: Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2. Aspirin 96-103 cyclin dependent kinase 2 Homo sapiens 135-139 27158383-5 2016 Additionally, ferulic acid induced G0/G1 phase arrest and down-regulated the expression of cell cycle-related protein, CDK 2, CDK 4, CDK 6, confirmed by flow cytometry assay and western blotting. ferulic acid 14-26 cyclin dependent kinase 2 Homo sapiens 119-124 26796279-9 2016 The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Curcumin 49-57 cyclin dependent kinase 2 Homo sapiens 104-108 26783196-10 2016 To suppress the expression of phosphorylated RB, we performed the knockdown of CDKs, which are known to phosphorylate RB. Rubidium 45-47 cyclin dependent kinase 2 Homo sapiens 79-83 26783196-10 2016 To suppress the expression of phosphorylated RB, we performed the knockdown of CDKs, which are known to phosphorylate RB. Rubidium 118-120 cyclin dependent kinase 2 Homo sapiens 79-83 26758421-2 2016 Here, we show that Bufalin can inhibit cervical cancer cell proliferation, block cell cycle in G2/M phase, induce cellular apoptosis and reduce cell metastasis through stimulation of p21(waf/cip1), p27(cip/kip), Bax and E-cadherin, and suppression of cyclin A, cyclin B1, CDK2, Bcl-2, Bcl-xl, MMP9 and SNAIL1. bufalin 19-26 cyclin dependent kinase 2 Homo sapiens 272-276 26840297-0 2016 Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs. Melatonin 0-9 cyclin dependent kinase 2 Homo sapiens 135-139 26450989-8 2016 We observed that SUMOylation regulated p27(Kip1) binding to CDK2, thereby governing its nuclear proteasomal degradation through the phosphorylation of threonine 187. Threonine 151-160 cyclin dependent kinase 2 Homo sapiens 60-64 26840297-6 2016 We observed the accumulation of melatonin-treated cells in the G1 phase due to the down-regulation of CDK 2 and 4. Melatonin 32-41 cyclin dependent kinase 2 Homo sapiens 102-113 26701207-2 2016 We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-gamma-induced expression of p27(Kip1) (p27) repressed Myc"s activity to suppress cellular senescence and differentiation. Serine 84-87 cyclin dependent kinase 2 Homo sapiens 44-48 26741853-0 2016 Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors. 7-azaindole dimer 77-88 cyclin dependent kinase 2 Homo sapiens 132-136 26741853-1 2016 From four molecules, inspired by the structural features of fascaplysin, with an interesting potential to inhibit cyclin-dependent kinases (CDKs), we designed a new series of tri-heterocyclic derivatives based on 1H-pyrrolo[2,3-b]pyridine (7-azaindole) and triazole heterocycles. pyrrolo(2, 3-b)pyridine 213-238 cyclin dependent kinase 2 Homo sapiens 140-144 26741853-1 2016 From four molecules, inspired by the structural features of fascaplysin, with an interesting potential to inhibit cyclin-dependent kinases (CDKs), we designed a new series of tri-heterocyclic derivatives based on 1H-pyrrolo[2,3-b]pyridine (7-azaindole) and triazole heterocycles. 7-azaindole dimer 240-251 cyclin dependent kinase 2 Homo sapiens 140-144 26741853-1 2016 From four molecules, inspired by the structural features of fascaplysin, with an interesting potential to inhibit cyclin-dependent kinases (CDKs), we designed a new series of tri-heterocyclic derivatives based on 1H-pyrrolo[2,3-b]pyridine (7-azaindole) and triazole heterocycles. Triazoles 257-265 cyclin dependent kinase 2 Homo sapiens 140-144 26686753-2 2016 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine derivatives are effective inhibitors of CDKs, among which the most promising inhibitor 12u demonstrates high binding affinity to CDK9 and attenuated binding affinity to other homologous kinases, such as CDK2. 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine 0-43 cyclin dependent kinase 2 Homo sapiens 84-88 26686753-2 2016 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine derivatives are effective inhibitors of CDKs, among which the most promising inhibitor 12u demonstrates high binding affinity to CDK9 and attenuated binding affinity to other homologous kinases, such as CDK2. 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine 0-43 cyclin dependent kinase 2 Homo sapiens 247-251 27771926-2 2016 Flavopiridol arrests cell cycle progression in the G1 or G2 phase by inhibiting the kinase activities of CDK1, CDK2, CDK4/6, and CDK7. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 111-115 26595527-0 2016 A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase. MK-8776 73-80 cyclin dependent kinase 2 Homo sapiens 103-107 26890070-10 2016 Consistent with these findings, a genome-scale pooled RNA interference screen revealed that toxic doses of MK-1775 are suppressed by CDK2 or Cyclin A2 knockdown. adavosertib 107-114 cyclin dependent kinase 2 Homo sapiens 133-137 27226901-4 2016 We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. Cisplatin 39-48 cyclin dependent kinase 2 Homo sapiens 149-174 27239332-3 2016 Previously, we found that cisplatin-induced kidney cell death was dependent on Cdk2 activation, and inhibition of Cdk2 protected cells from cisplatin-induced apoptosis. Cisplatin 26-35 cyclin dependent kinase 2 Homo sapiens 79-83 27239332-3 2016 Previously, we found that cisplatin-induced kidney cell death was dependent on Cdk2 activation, and inhibition of Cdk2 protected cells from cisplatin-induced apoptosis. Cisplatin 26-35 cyclin dependent kinase 2 Homo sapiens 114-118 27239332-3 2016 Previously, we found that cisplatin-induced kidney cell death was dependent on Cdk2 activation, and inhibition of Cdk2 protected cells from cisplatin-induced apoptosis. Cisplatin 140-149 cyclin dependent kinase 2 Homo sapiens 114-118 26771717-3 2016 In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). Serine 124-130 cyclin dependent kinase 2 Homo sapiens 65-90 26771717-3 2016 In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). Serine 124-130 cyclin dependent kinase 2 Homo sapiens 92-96 27239332-4 2016 Using an in vitro kination assay, we showed that Cdk2 phosphorylated Bcl-xL, an anti-apoptotic member of Bcl-2 family proteins, at serine 73. Serine 131-137 cyclin dependent kinase 2 Homo sapiens 49-53 26647836-4 2016 In addition, hesperetin blocked the progression of the cell cycle from G0/G1 to S phase, which was correlated with the decreased mRNA expression levels of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4, and the increased mRNA expression levels of p27. hesperetin 13-23 cyclin dependent kinase 2 Homo sapiens 201-206 26565382-0 2016 Molecular simulation studies on the binding selectivity of 2-anilino-4-(thiazol-5-yl)-pyrimidines in complexes with CDK2 and CDK7. 2-anilino-4-(thiazol-5-yl)-pyrimidines 59-97 cyclin dependent kinase 2 Homo sapiens 116-120 26565382-3 2016 In this study, three thiazo-5-yl-pyrimidines as CDK2 inhibitors with different selectivity over cyclin dependent kinase 7 (CDK7) were examined to study the selectivity mechanism using a combined approach of computational techniques of flexible docking, EasyMIFs, molecular electrostatic potential (MESP), natural bond orbital (NBO), molecular dynamics (MD) simulations, and binding free energy calculations. thiazo-5-yl-pyrimidines 21-44 cyclin dependent kinase 2 Homo sapiens 48-52 27997894-11 2016 In addition, zedoarondiol activated AMPK and ACC, inhibited the phosphorylation of mTOR and p70S6K, increased the expression of p53 and p21, and decreased the expression of CDK2 and cyclin E. Compound C (an AMPK inhibitor) abrogated, whereas 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR, an AMPK activator) enhanced zedoarondiol-mediated inhibition of VSMCs proliferation and DNA synthesis. zedoarondiol 13-25 cyclin dependent kinase 2 Homo sapiens 173-177 26590797-9 2016 Moreover, IAZP augmented the doxorubicin-induced degradation of p21, activation of p53, CDK2, caspase 3/7 and phosphorylation of Rb protein. Doxorubicin 29-40 cyclin dependent kinase 2 Homo sapiens 88-92 26328598-0 2015 Correction to N-(Cycloalkylamino)acyl-2-aminothiazole Inhibitors of Cyclin-Dependent Kinase 2. n-(cycloalkylamino)acyl-2-aminothiazole 14-53 cyclin dependent kinase 2 Homo sapiens 68-93 27098147-10 2016 The observed elevated expression of p53 and p16 by RTX may contribute to the reduction of cyclin A/CDK2. raltitrexed 51-54 cyclin dependent kinase 2 Homo sapiens 99-103 26690546-0 2015 Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells. Chloroquine 0-11 cyclin dependent kinase 2 Homo sapiens 80-84 26690546-0 2015 Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells. Etoposide 23-32 cyclin dependent kinase 2 Homo sapiens 80-84 26690546-7 2015 Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells. Etoposide 124-127 cyclin dependent kinase 2 Homo sapiens 38-42 26690546-7 2015 Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells. Etoposide 124-127 cyclin dependent kinase 2 Homo sapiens 69-73 26690546-10 2015 Chloroquine alleviated CDK2 and ERK, but not Chk2, activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells. Chloroquine 0-11 cyclin dependent kinase 2 Homo sapiens 23-27 26690546-12 2015 In summary, we have demonstrated that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity, thus preventing genomic instability and recurrence of ACT. Chloroquine 38-49 cyclin dependent kinase 2 Homo sapiens 149-153 26598692-9 2015 Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the gamma-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. gamma-h2ax 80-90 cyclin dependent kinase 2 Homo sapiens 35-39 26598692-9 2015 Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the gamma-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. gamma-h2ax 80-90 cyclin dependent kinase 2 Homo sapiens 52-56 26677902-0 2015 Induction of cell cycle arrest via the p21, p27-cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol. smmc 75-79 cyclin dependent kinase 2 Homo sapiens 59-63 26677902-0 2015 Induction of cell cycle arrest via the p21, p27-cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol. Clioquinol 103-113 cyclin dependent kinase 2 Homo sapiens 59-63 26677902-5 2015 Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment with clioquinol. Clioquinol 126-136 cyclin dependent kinase 2 Homo sapiens 52-56 26677902-6 2015 The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27-cyclin E,A/Cdk2 pathway. Clioquinol 49-59 cyclin dependent kinase 2 Homo sapiens 156-160 26451628-6 2015 Our results illustrate that PCB29-pQ increases the S-phase cell population by down-regulating cyclins A/D1/E, cyclin-dependent kinases (CDK 2/4/6), and cell division cycle 25A (CDC25A) and up-regulating p21/p27 protein expressions. 2,3,5-trichloro-6-phenyl-(1,4)benzoquinone 28-36 cyclin dependent kinase 2 Homo sapiens 136-145 26870186-8 2016 Cell cycle-associated proteins, including phosphorylated protein kinase B, cyclin D1, cyclin dependent kinase (CDK) 2 and CDK6 were downregulated by BCTC, while phosphorylated glycogen synthase kinase 3beta was upregulated. BCTC 149-153 cyclin dependent kinase 2 Homo sapiens 86-117 26658815-10 2015 NADPH oxidase inhibitor apocynin pretreatment partially abolished UII-increased phosphorylation of PI3K/Akt and ERK, expression of cyclin E/cyclin-dependent kinase 2. acetovanillone 24-32 cyclin dependent kinase 2 Homo sapiens 140-165 26198005-0 2015 Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-Dependent Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In Vitro. 3aH-pyrazolo[4,3-d]pyrimidine 22-47 cyclin dependent kinase 2 Homo sapiens 61-93 26198005-2 2015 We prepared and studied a series of 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines, a new CDK inhibitor scaffold, to assess their CDK2 inhibitory and antiproliferative activities. 3,5,7-trisubstituted pyrazolo[4,3-d]pyrimidines 36-83 cyclin dependent kinase 2 Homo sapiens 131-135 26555773-0 2015 Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation. diacerein 0-9 cyclin dependent kinase 2 Homo sapiens 111-115 26555773-10 2015 mRNA and protein analysis revealed that diacerein induced a down-regulation of the cyclin B1-CDK1 complex and a reduction in CDK2 expression. diacerein 40-49 cyclin dependent kinase 2 Homo sapiens 125-129 26398439-0 2015 Adapalene inhibits the activity of cyclin-dependent kinase 2 in colorectal carcinoma. Adapalene 0-9 cyclin dependent kinase 2 Homo sapiens 35-60 26398439-8 2015 To the best of our knowledge, the present study was the first to indicate that ADA inhibits CDK2 and is a potential candidate drug for the treatment of human colorectal cancer. Adapalene 79-82 cyclin dependent kinase 2 Homo sapiens 92-96 26492346-6 2015 PNAP-6h led to cell arrest at the S phase, most likely due to increasing levels of p21 and p27 and decreasing levels of cyclin D1, CDK4, cyclin E, and CDK2. 6H 5-7 cyclin dependent kinase 2 Homo sapiens 151-155 26181229-4 2015 Aspidin PB induced changes in the cell cycle regulators (cyclin A, pRb, CDK2, p53, and p21), which caused cell cycle arrest in the S phase. aspidin PB 0-10 cyclin dependent kinase 2 Homo sapiens 72-76 26250568-4 2015 Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. magnolol 0-8 cyclin dependent kinase 2 Homo sapiens 193-197 26158339-3 2015 We chose CDK2 as a model system to study the DFG in-out transition on a target that was thought to have an inaccessible DFG-out conformation. 1,3-Diphenylguanidine 45-48 cyclin dependent kinase 2 Homo sapiens 9-13 26158339-7 2015 Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine-phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. aminopyrimidine-phenyl urea 78-105 cyclin dependent kinase 2 Homo sapiens 57-61 26158339-7 2015 Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine-phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. aminopyrimidine-phenyl urea 78-105 cyclin dependent kinase 2 Homo sapiens 209-213 26158339-7 2015 Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine-phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. K03861 117-123 cyclin dependent kinase 2 Homo sapiens 57-61 26158339-7 2015 Using protein crystallography structural analysis of the CDK2 complex with an aminopyrimidine-phenyl urea inhibitor (K03861) revealed a canonical type II binding mode and the first available type II inhibitor CDK2 cocrystal structure. K03861 117-123 cyclin dependent kinase 2 Homo sapiens 209-213 26158339-11 2015 The presented data also provide the foundation for a new class of slow off-rate cyclin-competitive CDK2 inhibitors targeting the inactive DFG-out state of this important kinase target. 1,3-Diphenylguanidine 138-141 cyclin dependent kinase 2 Homo sapiens 99-103 26139602-3 2015 In this study we have identified new phosphorylation sites on Sox2 and have further demonstrated that Cdk2-mediated Sox2 phosphorylation at Ser-39 and Ser-253 is required for establishing the pluripotent state during reprogramming but is dispensable for ESC maintenance. Serine 140-143 cyclin dependent kinase 2 Homo sapiens 102-106 26320860-2 2015 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. NU6102 0-64 cyclin dependent kinase 2 Homo sapiens 129-133 26320860-2 2015 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. NU6102 66-72 cyclin dependent kinase 2 Homo sapiens 129-133 26320860-2 2015 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Adenosine Triphosphate 100-103 cyclin dependent kinase 2 Homo sapiens 129-133 26320860-2 2015 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Sulfonamides 53-64 cyclin dependent kinase 2 Homo sapiens 129-133 26320860-2 2015 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Lysine 199-205 cyclin dependent kinase 2 Homo sapiens 129-133 26320860-3 2015 Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. 6-(cyclohexylmethoxy)-n-(4-(vinylsulfonyl)phenyl)-9h-purin-2-amine 49-115 cyclin dependent kinase 2 Homo sapiens 14-18 26320860-3 2015 Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. 6-(cyclohexylmethoxy)-n-(4-(vinylsulfonyl)phenyl)-9h-purin-2-amine 49-115 cyclin dependent kinase 2 Homo sapiens 152-156 26320860-3 2015 Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. NU6300 117-123 cyclin dependent kinase 2 Homo sapiens 14-18 26320860-3 2015 Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. NU6300 117-123 cyclin dependent kinase 2 Homo sapiens 152-156 26320860-4 2015 Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 22-28 cyclin dependent kinase 2 Homo sapiens 144-148 26320860-5 2015 NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds. NU6300 0-6 cyclin dependent kinase 2 Homo sapiens 29-33 26139602-3 2015 In this study we have identified new phosphorylation sites on Sox2 and have further demonstrated that Cdk2-mediated Sox2 phosphorylation at Ser-39 and Ser-253 is required for establishing the pluripotent state during reprogramming but is dispensable for ESC maintenance. Serine 151-154 cyclin dependent kinase 2 Homo sapiens 102-106 26359868-10 2015 As2O3 also decreased the protein expressions of cyclin D1, cyclin E, cyclin B1, cyclin-dependent kinase (CDK) 2, and CDK4, but did not affect the protein expressions of p21 and p27. Arsenic Trioxide 0-5 cyclin dependent kinase 2 Homo sapiens 80-111 26139602-5 2015 Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser-39 and Ser-253 in vitro. Serine 63-66 cyclin dependent kinase 2 Homo sapiens 0-4 26139602-5 2015 Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser-39 and Ser-253 in vitro. Serine 74-77 cyclin dependent kinase 2 Homo sapiens 0-4 26201988-9 2015 The levels of the cell cycle-related genes and proteins (cyclin D1, cyclin E and CDK2) were reduced by amantadine, and apoptosis was significantly induced. Amantadine 103-113 cyclin dependent kinase 2 Homo sapiens 81-85 26330754-6 2015 This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). murrayafoline A 34-49 cyclin dependent kinase 2 Homo sapiens 228-233 26295255-4 2015 Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Docosahexaenoic Acids 35-38 cyclin dependent kinase 2 Homo sapiens 186-190 26141948-4 2015 The action of LY2606368 is dependent upon inhibition of CHK1 and the corresponding increase in CDC25A activation of CDK2, which increases the number of replication forks while reducing their stability. prexasertib 14-23 cyclin dependent kinase 2 Homo sapiens 116-120 26151768-9 2015 In G28 cells, a dose-dependent induction of CDK2, p21 and cyclin D was observed between 10 and 50 microM roscovitine after 72 h, however, at the highest concentration of 100 microM, all investigated genes were downregulated. Roscovitine 105-116 cyclin dependent kinase 2 Homo sapiens 44-48 26151768-11 2015 In A172 cells, roscovitine led to G2/M arrest and induced apoptosis, an effect accompanied by induced p21 and a reduced expression of CDK2, 7 and 9 and cyclins A and E. Roscovitine 15-26 cyclin dependent kinase 2 Homo sapiens 134-138 26295255-4 2015 Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Eicosapentaenoic Acid 43-46 cyclin dependent kinase 2 Homo sapiens 186-190 24474168-7 2015 Induction of cell-cycle arrest by CPT-11 was associated with changes in expression of key cell-cycle regulators such as CDK2, Chk2, and cyclin D in HL-60 cells. Irinotecan 34-40 cyclin dependent kinase 2 Homo sapiens 120-124 26219338-0 2015 Cyclin E/Cdk2-dependent phosphorylation of Mcl-1 determines its stability and cellular sensitivity to BH3 mimetics. BH 3 102-105 cyclin dependent kinase 2 Homo sapiens 9-13 26219338-2 2015 Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid 194-197 cyclin dependent kinase 2 Homo sapiens 28-32 26219338-2 2015 Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid 206-209 cyclin dependent kinase 2 Homo sapiens 28-32 26219338-3 2015 Cyclin E levels were elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT-737-resistant compared to parental cells. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid 97-100 cyclin dependent kinase 2 Homo sapiens 78-82 26147897-9 2015 We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. Fluspirilene 40-52 cyclin dependent kinase 2 Homo sapiens 157-161 26147897-9 2015 We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. Fluspirilene 40-52 cyclin dependent kinase 2 Homo sapiens 215-219 26147897-14 2015 These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. Fluspirilene 48-60 cyclin dependent kinase 2 Homo sapiens 76-80 26057861-2 2015 Here, we report a series of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3beta inhibitors by rational-design and synthesis, which show high selectivity against GSK-3beta over Cyclin-dependent kinase 2 (CDK2), and significantly activate the cellular Wnt/beta-catenin pathway. benzo[e]isoindole-1,3-dione 28-55 cyclin dependent kinase 2 Homo sapiens 187-212 26057861-2 2015 Here, we report a series of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3beta inhibitors by rational-design and synthesis, which show high selectivity against GSK-3beta over Cyclin-dependent kinase 2 (CDK2), and significantly activate the cellular Wnt/beta-catenin pathway. benzo[e]isoindole-1,3-dione 28-55 cyclin dependent kinase 2 Homo sapiens 214-218 25947565-2 2015 CDK1/CDK2 inhibitors, such as dinaciclib, combined with anthracyclines, were synergistic in decreasing viability of TNBC cell lines. dinaciclib 30-40 cyclin dependent kinase 2 Homo sapiens 5-9 25738368-5 2015 In addition, simvastatin arrested cells in the G0/G1 phase of the cell cycle, downregulated the protein expression levels of cyclin D1 and cyclin-dependent kinase (CDK)2, mediated the mitochondria-dependent caspase cascade by increasing the protein expression levels of caspase-3, -8 and -9, and downregulated the protein expression of X-linked inhibitor of apoptosis, which induced cell apoptosis. Simvastatin 13-24 cyclin dependent kinase 2 Homo sapiens 164-169 25870074-14 2015 Roscovitine, a CDK2 inhibitor, antagonized the anti-CMV activities of AS and dimer 606. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 15-19 25870074-15 2015 These data suggest that cell cycle modulation through CDKs and pRb might play a role in the anti-CMV activities of artemisinins. Artemisinins 115-127 cyclin dependent kinase 2 Homo sapiens 54-58 25942479-5 2015 The aim was to investigate whether R-roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin-dependent kinase 2/cyclin E signaling pathway. Roscovitine 35-48 cyclin dependent kinase 2 Homo sapiens 109-134 26309548-5 2015 The expression levels of Cyclin A, CDK2, and Cyclin D1 were downregulated by baicalin treatment. baicalin 77-85 cyclin dependent kinase 2 Homo sapiens 35-39 25962959-2 2015 Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. dinaciclib 0-10 cyclin dependent kinase 2 Homo sapiens 54-58 25682067-6 2015 The predictions were validated and tested by comparison to more than 1500 crystallographic water positions in 20 hydrated protein molecules including enzymes of biomedical importance such as cyclin-dependent kinase 2. Water 91-96 cyclin dependent kinase 2 Homo sapiens 191-216 26054755-4 2015 Application of this iterative workflow to optimization of the CDK2 inhibitor Seliciclib (CYC202, R-roscovitine) generated solution molecules in desired physicochemical property space. Roscovitine 97-110 cyclin dependent kinase 2 Homo sapiens 62-66 26026083-0 2015 Induction of G1 Arrest by SB265610 Involves Cyclin D3 Down-regulation and Suppression of CDK2 (Thr160) Phosphorylation. 1-(2-bromophenyl)-3-(7-cyano-3H-benzotriazol-4-yl)urea 26-34 cyclin dependent kinase 2 Homo sapiens 89-93 25714087-5 2015 Results show that chabamide inhibited the growth of K562/ADR cells in a dose-dependent and time-dependent manner, and significantly inhibited cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious increase in p21 and decrease in cyclin D1 and CDK2/4/6 protein expression. chabamide 18-27 cyclin dependent kinase 2 Homo sapiens 285-293 26026083-8 2015 Pharmacological interference with p38MAPK significantly abrogated SB265610-induced G1 arrest and normalized the expression of cyclin D3, with restoration of its exclusive binding to CDK6, but with weak recovery of CDK2 (Thr160) hypo-phosphorylation. 1-(2-bromophenyl)-3-(7-cyano-3H-benzotriazol-4-yl)urea 66-74 cyclin dependent kinase 2 Homo sapiens 214-218 25946558-5 2015 Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. tbbx 142-146 cyclin dependent kinase 2 Homo sapiens 46-50 26189300-10 2015 Furthermore, AMP increased p21(CIP1) expression but decreased cyclin A and CDK2 expression after AMP exposure. ampelopsin 13-16 cyclin dependent kinase 2 Homo sapiens 75-79 26189300-10 2015 Furthermore, AMP increased p21(CIP1) expression but decreased cyclin A and CDK2 expression after AMP exposure. ampelopsin 97-100 cyclin dependent kinase 2 Homo sapiens 75-79 26552178-7 2015 According to the results of Real-time PCR and Western blot, TMP could down-regulate the expression of apoptosis-related molecule bcl-2, cycle-related protein cyclin E1 and CDK2 and up-regulate caspase-3 and P27. tetramethylpyrazine 60-63 cyclin dependent kinase 2 Homo sapiens 172-176 26207228-2 2015 It is a broad-range purine inhibitor, which inhibits CDK1, CDK2, CDK5 and CDK7, but is a poor inhibitor for CDK4 and CDK6. purine 20-26 cyclin dependent kinase 2 Homo sapiens 59-63 25908517-0 2015 Discovery of novel indirubin-3"-monoxime derivatives as potent inhibitors against CDK2 and CDK9. indirubin-3" 19-31 cyclin dependent kinase 2 Homo sapiens 82-86 25908517-0 2015 Discovery of novel indirubin-3"-monoxime derivatives as potent inhibitors against CDK2 and CDK9. monoxime 32-40 cyclin dependent kinase 2 Homo sapiens 82-86 25736292-2 2015 We show here that cyclin-A-CDK2 also negatively regulates CIZ1 activity by phosphorylation at threonines 144, 192 and 293. Threonine 94-104 cyclin dependent kinase 2 Homo sapiens 27-31 25918937-4 2015 Until now, in the monomeric CDK2 structure, three binding sites have been reported, including the adenosine triphosphate (ATP) binding site (Site I) and two non-competitive binding sites (Site II and III). Adenosine Triphosphate 98-120 cyclin dependent kinase 2 Homo sapiens 28-32 25918937-4 2015 Until now, in the monomeric CDK2 structure, three binding sites have been reported, including the adenosine triphosphate (ATP) binding site (Site I) and two non-competitive binding sites (Site II and III). Adenosine Triphosphate 122-125 cyclin dependent kinase 2 Homo sapiens 28-32 25754137-0 2015 Molecular dynamics study of the inhibitory effects of ChEMBL474807 on the enzymes GSK-3beta and CDK-2. indazole-benzimidazole, 5 54-66 cyclin dependent kinase 2 Homo sapiens 96-101 25860957-7 2015 ING5 is phosphorylated at a single site, threonine 152, by cyclin E/CDK2 and cyclin A/CDK2 in vitro. Threonine 41-50 cyclin dependent kinase 2 Homo sapiens 68-72 25860957-7 2015 ING5 is phosphorylated at a single site, threonine 152, by cyclin E/CDK2 and cyclin A/CDK2 in vitro. Threonine 41-50 cyclin dependent kinase 2 Homo sapiens 86-90 25860957-9 2015 Furthermore overexpression of cyclin E/CDK2 stimulates while the CDK2 inhibitor p27KIP1 represses phosphorylation at threonine 152. Threonine 117-126 cyclin dependent kinase 2 Homo sapiens 39-43 25860957-9 2015 Furthermore overexpression of cyclin E/CDK2 stimulates while the CDK2 inhibitor p27KIP1 represses phosphorylation at threonine 152. Threonine 117-126 cyclin dependent kinase 2 Homo sapiens 65-69 25768698-3 2015 We serendipitously found that firefly luciferin inhibited the CDK2/Cyclin A protein kinase. D-luciferin 38-47 cyclin dependent kinase 2 Homo sapiens 62-66 25825542-2 2015 Recently, using systematic time studies of neuroblastoma cell growth, we better defined the G1 arrest caused by iron chelation to a point in mid-G1, where cyclin E protein is present, but the cyclin E/CDK2 complex kinase activity is inhibited. Iron 112-116 cyclin dependent kinase 2 Homo sapiens 201-205 25914804-0 2015 Discovery of novel 5-fluoro-N2,N4-diphenylpyrimidine-2,4-diamines as potent inhibitors against CDK2 and CDK9. 5-fluoro-n2,n4-diphenylpyrimidine-2,4-diamines 19-65 cyclin dependent kinase 2 Homo sapiens 95-99 25434397-7 2015 In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. Deoxycholic Acid 77-80 cyclin dependent kinase 2 Homo sapiens 50-54 25573651-5 2015 Western blot analysis indicated that GA mediated G1-phase cell cycle arrest by upregulation of cyclin-dependent kinase inhibitors (CKIs) (p18, p16, p27 and p21) and inhibition of cyclins (cyclin-D1, -D3 and -E) and cyclin-dependent kinases (CDKs) (CDK4, 6 and 2). Glycyrrhetinic Acid 37-39 cyclin dependent kinase 2 Homo sapiens 241-245 25540387-7 2015 Identification of CTD-host interactions indicated that CDK2 binding by CTD may mediate its inhibitory effect on DHBc phosphorylation and reverse transcription via competition with DHBc for the host kinase, whereas importin alpha binding by CTD may contribute to inhibition of CCC DNA production by competitively blocking the nuclear import of viral nucleocapsids. dhbc 112-116 cyclin dependent kinase 2 Homo sapiens 55-59 25540387-7 2015 Identification of CTD-host interactions indicated that CDK2 binding by CTD may mediate its inhibitory effect on DHBc phosphorylation and reverse transcription via competition with DHBc for the host kinase, whereas importin alpha binding by CTD may contribute to inhibition of CCC DNA production by competitively blocking the nuclear import of viral nucleocapsids. dhbc 180-184 cyclin dependent kinase 2 Homo sapiens 55-59 25825542-4 2015 Initial studies showed in the presence of DFO, these cells have high levels of p27 and after reversal of iron chelation p27 is degraded allowing for CDK2 kinase activity. Deferoxamine 42-45 cyclin dependent kinase 2 Homo sapiens 149-153 25548279-4 2015 By taking the approach of mass spectrometry, we identified that PHF8 Ser-844 is phosphorylated by cyclin E-CDK2. Serine 69-72 cyclin dependent kinase 2 Homo sapiens 107-111 25548279-9 2015 In addition, we found that cyclin E-CDK2-mediated phosphorylation of PHF8 Ser-844 promotes PHF8-dependent rRNA transcription in luciferase reporter assays and real-time PCR. Serine 74-77 cyclin dependent kinase 2 Homo sapiens 36-40 25557169-6 2015 Consequently, CDK2 inhibition sensitizes cyclin E1-driven but not RAS-driven ovarian cancer cells to platinum-based chemotherapy. Platinum 101-109 cyclin dependent kinase 2 Homo sapiens 14-18 28962365-7 2015 In both cell lines, GTN induced G0/G1 cell cycle arrest, delayed S phase entry of cells and inhibited anchorage-independent cell growth which might be attributed to the upregulation of CKIs and downregulation of several positive cell cycle regulators, including CDC28 protein kinase regulator subunit 1B, cyclin E1 and D1, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, E2F transcription factor 1 and/or transcription factor Dp-1. goniothalamin 20-23 cyclin dependent kinase 2 Homo sapiens 323-348 28962365-7 2015 In both cell lines, GTN induced G0/G1 cell cycle arrest, delayed S phase entry of cells and inhibited anchorage-independent cell growth which might be attributed to the upregulation of CKIs and downregulation of several positive cell cycle regulators, including CDC28 protein kinase regulator subunit 1B, cyclin E1 and D1, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, E2F transcription factor 1 and/or transcription factor Dp-1. goniothalamin 20-23 cyclin dependent kinase 2 Homo sapiens 350-354 25541464-0 2015 Yeast as a model system to screen purine derivatives against human CDK1 and CDK2 kinases. purine 34-40 cyclin dependent kinase 2 Homo sapiens 76-80 25541464-4 2015 In the present study, taking advantage of the fact that deletion of the yeast CDC28 gene is functionally complemented by human CDK1 or CDK2, we set up an in vivo screen system to evaluate the inhibitory potency of purine derivatives against these two human Cdks. purine 214-220 cyclin dependent kinase 2 Homo sapiens 135-139 25785018-4 2015 Sophoridine also triggered significant down-regulated the expression of p27, CDK2, Survivin, Livin, Bcl-2, E2F1 and the transcriptional activity of FoxM1, NF-kappab and AP-1, meanwhile, up-regulated the expression of caspase-3/8, p53, Smac, c-JNK and p38-MAPK. matrine 0-11 cyclin dependent kinase 2 Homo sapiens 77-81 25395429-2 2015 Dinaciclib is a novel potent small molecule inhibitor of cyclin-dependent kinases (CDK)1, CDK2, CDK5, and CDK9. dinaciclib 0-10 cyclin dependent kinase 2 Homo sapiens 90-94 24336329-4 2015 Interaction with MIF4GD led to the stabilization of p27 both in the nucleus and in the cytoplasm in hepatocellular carcinoma (HCC) cells as a result of suppressed phosphorylation of p27 by CDK2 at threonine187. threonine187 197-209 cyclin dependent kinase 2 Homo sapiens 189-193 25411358-7 2015 Removal of TPA from the growth medium resulted in the rapid induction of BCL2, increasing the ratio of anti-: pro-apoptotic proteins, together with overexpression of Cyclin A/CDK2 proteins. terephthalic acid 11-14 cyclin dependent kinase 2 Homo sapiens 175-179 25927932-5 2015 Here, we show that knockdown of cyclin D3 a partner of CDK6 and E2 a partner of CDK2 had a major impact in SAMHD1 phosphorylation and inactivation and led to decreased dNTP levels and inhibition of HIV-1 at the reverse transcription step in primary human macrophages. Parathion 168-172 cyclin dependent kinase 2 Homo sapiens 80-84 25927932-8 2015 Our results confirm the fundamental role of the CDK6-cyclin D3 pair in controlling CDK2-dependent SAMHD1 phosphorylation and dNTP pool in primary macrophages. Parathion 125-129 cyclin dependent kinase 2 Homo sapiens 83-87 25872479-4 2015 All of the Akt/MMP2/MMP9 pathway, Akt/Bad pathway, and Akt/Gsk3beta/CDK2 pathway could be inhibited by fangchinoline through inhibition of PI3K. fangchinoline 103-116 cyclin dependent kinase 2 Homo sapiens 68-72 25870953-0 2015 The anticancer activity of the substituted pyridone-annelated isoindigo (5"-Cl) involves G0/G1 cell cycle arrest and inactivation of CDKs in the promyelocytic leukemia cell line HL-60. Pyridones 43-51 cyclin dependent kinase 2 Homo sapiens 133-137 25870953-0 2015 The anticancer activity of the substituted pyridone-annelated isoindigo (5"-Cl) involves G0/G1 cell cycle arrest and inactivation of CDKs in the promyelocytic leukemia cell line HL-60. isoindigo (5"-cl) 62-79 cyclin dependent kinase 2 Homo sapiens 133-137 25870953-7 2015 Furthermore, 5"-Cl treatment significantly inhibited expression of D-cyclins, CDK2 and CDK4 and suppressed phosphorylation of the retinoblastoma protein Rb, whereas it increased the level of CKI p21. 5"-cl 13-18 cyclin dependent kinase 2 Homo sapiens 78-82 25870953-8 2015 Molecular modelling experiments show that 5"-Cl may compete with ATP for binding to the catalytic subunit of CDK2 and CDK4 that could lead to inhibition of these enzymes. 5"-cl 42-47 cyclin dependent kinase 2 Homo sapiens 109-113 25870953-8 2015 Molecular modelling experiments show that 5"-Cl may compete with ATP for binding to the catalytic subunit of CDK2 and CDK4 that could lead to inhibition of these enzymes. Adenosine Triphosphate 65-68 cyclin dependent kinase 2 Homo sapiens 109-113 25870953-9 2015 Indeed, 5"-Cl inhibited the kinase activity of CDK2 and CDK4 both in cell free systems and in treated cells. 5"-cl 8-13 cyclin dependent kinase 2 Homo sapiens 47-51 26209183-3 2015 Analysis of energy contributions indicate that electrostatic interaction energy dictates the selectivity of ATP competitive inhibitors against CDK-2. Adenosine Triphosphate 108-111 cyclin dependent kinase 2 Homo sapiens 143-148 25527123-10 2014 The S arrest and the activation of ATM-Chk1/Chk2-Cdc25A-Cdk2 pathways induced by SC-III3 in HepG2 cells could be efficiently abrogated by pretreatments of either Ku55933 (an inhibitor of ATM) or UCN-01 (an inhibitor of Chk1/Chk2). 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one 162-169 cyclin dependent kinase 2 Homo sapiens 56-60 25902329-0 2015 Molecular insights of benzodipyrazole as CDK2 inhibitors: combined molecular docking, molecular dynamics, and 3D QSAR studies. benzodipyrazole 22-37 cyclin dependent kinase 2 Homo sapiens 41-45 25902329-1 2015 Benzodipyrazoles have been previously evaluated for their in vitro CDK2 inhibitory activity. benzodipyrazoles 0-16 cyclin dependent kinase 2 Homo sapiens 67-71 25868784-5 2015 Silibinin with 0.5 or 5 microM arsenic induced G1 or G2/M phase arrest, respectively, and decreased the protein levels of CDK2, -4, and -6 and cyclin D1, D3, and E and increased CDK inhibitors p21 and p27. Silybin 0-9 cyclin dependent kinase 2 Homo sapiens 122-138 25868784-5 2015 Silibinin with 0.5 or 5 microM arsenic induced G1 or G2/M phase arrest, respectively, and decreased the protein levels of CDK2, -4, and -6 and cyclin D1, D3, and E and increased CDK inhibitors p21 and p27. Arsenic 31-38 cyclin dependent kinase 2 Homo sapiens 122-138 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. Nitrogen 47-48 cyclin dependent kinase 2 Homo sapiens 115-140 25606576-9 2014 MAA-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and CDK2 expression at the late time. methoxyacetic acid 0-3 cyclin dependent kinase 2 Homo sapiens 170-174 25293876-6 2014 Quercetin treatment resulted in an increased cell arrest in G1 phase of the cell cycle, with pronounced decrease in CDK2, CDK6, cyclin D, cyclin E, and cyclin A proteins, decreased Rb phosphorylation and increased p21 and p27 expression. Quercetin 0-9 cyclin dependent kinase 2 Homo sapiens 116-120 25550687-0 2014 CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro. Docetaxel 88-97 cyclin dependent kinase 2 Homo sapiens 0-4 25550687-13 2014 The data indicates that CDK2-AP1 can induce sensitivity to docetaxel treatment in breast cancer cells. Docetaxel 59-68 cyclin dependent kinase 2 Homo sapiens 24-28 25438765-7 2014 The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity. Adenosine Triphosphate 46-49 cyclin dependent kinase 2 Homo sapiens 96-100 25217392-1 2014 PURPOSE: Dinaciclib is a novel selective inhibitor of cyclin-dependent kinase (CDK)1, CDK2, CDK5, and CDK9. dinaciclib 9-19 cyclin dependent kinase 2 Homo sapiens 86-90 25435354-8 2014 After 24h, Cd treatment downregulated the expression of CHEK1, CHEK2 and CDK2 genes and upregulated the expression of CCNE1 gene. Cadmium 11-13 cyclin dependent kinase 2 Homo sapiens 73-77 25364462-9 2014 Mass spectroscopic analysis of cyclin O co-expressed with CDK2 revealed that the 81st serine residue of cyclin O was phosphorylated. Serine 86-92 cyclin dependent kinase 2 Homo sapiens 58-62 25364462-12 2014 These results suggest that cyclin O is a novel cyclin family protein that regulates CDK2 kinase activity, which is mediated by the phosphorylation of the 81st serine residue of cyclin O. Serine 159-165 cyclin dependent kinase 2 Homo sapiens 84-88 25242120-6 2014 The results indicated that silymarin effectively suppressed cell growth in a dose- and time-dependent manner, and arrested cell cycle progression at G1/S phase in A2780s and PA-1 cells via up-regulation of p53, p21, and p27 protein expression, and down-regulation of CDK2 protein expression. Silymarin 27-36 cyclin dependent kinase 2 Homo sapiens 267-271 25155598-0 2014 Phenyl-1-Pyridin-2yl-ethanone-based iron chelators increase IkappaB-alpha expression, modulate CDK2 and CDK9 activities, and inhibit HIV-1 transcription. phenyl-1-pyridin-2yl-ethanone 0-29 cyclin dependent kinase 2 Homo sapiens 95-99 25155598-0 2014 Phenyl-1-Pyridin-2yl-ethanone-based iron chelators increase IkappaB-alpha expression, modulate CDK2 and CDK9 activities, and inhibit HIV-1 transcription. Iron 36-40 cyclin dependent kinase 2 Homo sapiens 95-99 25155598-3 2014 We previously showed that chelation of intracellular iron inhibits CDK2 and CDK9 activities and suppresses HIV-1 transcription, but the mechanism of the inhibition was not understood. Iron 53-57 cyclin dependent kinase 2 Homo sapiens 67-71 25155598-8 2014 The iron chelators inhibited CDK2 activity and reduced the amount of CDK9/cyclin T1 in the large P-TEFb complex. Iron 4-8 cyclin dependent kinase 2 Homo sapiens 29-33 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. Nitrogen 47-48 cyclin dependent kinase 2 Homo sapiens 142-146 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. alkyl 49-54 cyclin dependent kinase 2 Homo sapiens 115-140 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. alkyl 49-54 cyclin dependent kinase 2 Homo sapiens 142-146 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. substituted isoindigo 63-84 cyclin dependent kinase 2 Homo sapiens 115-140 25151579-0 2014 Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3beta (GSK-3beta) phosphorylation inhibitors. substituted isoindigo 63-84 cyclin dependent kinase 2 Homo sapiens 142-146 25046358-7 2014 Moreover, D261 induced cell cycle arrest with a reduced expression of various G 1/S transition-related molecules including cyclin D1, cyclin E1, CDK4, and CDK2, but without influencing apoptosis in NSCLC cells. d261 10-14 cyclin dependent kinase 2 Homo sapiens 155-159 25290691-1 2014 Most inhibitors of Cyclin-dependent kinase 2 (CDK2) target its ATP-binding pocket. Adenosine Triphosphate 63-66 cyclin dependent kinase 2 Homo sapiens 19-44 25290691-1 2014 Most inhibitors of Cyclin-dependent kinase 2 (CDK2) target its ATP-binding pocket. Adenosine Triphosphate 63-66 cyclin dependent kinase 2 Homo sapiens 46-50 24970653-10 2014 Significantly, CD44+/CD24-/Low CSCs displayed resistance to conventional chemotherapy but higher sensitivity to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor, demonstrating that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44+/CD24-/Low CSC subpopulation in IBC. SU 9516 112-118 cyclin dependent kinase 2 Homo sapiens 131-156 25050564-2 2014 Annexin V/propidium iodide staining, MTT assay and western blot analysis revealed that resveratrol induced cycle arrest in the two cell lines, which was evidenced by cell cycle analysis and changes in the expression of the cell cycle proteins cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, proliferating cell nuclear antigen and P21. Resveratrol 87-98 cyclin dependent kinase 2 Homo sapiens 243-274 25074870-4 2014 The amount of the unphosphorylated wild-type yellow fluorescent protein-hPXR fusion protein but not the T290A mutant increased on Phos-tag gels in response to stimulations with rifampicin and cyclin-dependent kinase 2 inhibitor roscovitine, and a marked increase was observed in the unphosphorylated levels of the T290A mutant in nontreated cells. Roscovitine 228-239 cyclin dependent kinase 2 Homo sapiens 192-217 25584078-3 2015 Blocking the cyclin substrate recruitment on CBG is an alternative approach to override the specificity hurdle of the currently available ATP site targeting CDK2 inhibitors. Adenosine Triphosphate 138-141 cyclin dependent kinase 2 Homo sapiens 157-161 25584078-4 2015 Greater understanding of the interaction of CDK2/cyclin A complex with p27 (negative regulator) reveals that the Leu-Phe-Gly (LFG) motif region of p27 binds with the CBG site of cyclin A to arrest the malignant cell proliferation that induces apoptosis. Leu-Phe-Gly 113-124 cyclin dependent kinase 2 Homo sapiens 44-48 25584078-4 2015 Greater understanding of the interaction of CDK2/cyclin A complex with p27 (negative regulator) reveals that the Leu-Phe-Gly (LFG) motif region of p27 binds with the CBG site of cyclin A to arrest the malignant cell proliferation that induces apoptosis. lfg 126-129 cyclin dependent kinase 2 Homo sapiens 44-48 24970653-10 2014 Significantly, CD44+/CD24-/Low CSCs displayed resistance to conventional chemotherapy but higher sensitivity to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor, demonstrating that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44+/CD24-/Low CSC subpopulation in IBC. SU 9516 112-118 cyclin dependent kinase 2 Homo sapiens 158-162 24970653-10 2014 Significantly, CD44+/CD24-/Low CSCs displayed resistance to conventional chemotherapy but higher sensitivity to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor, demonstrating that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44+/CD24-/Low CSC subpopulation in IBC. SU 9516 112-118 cyclin dependent kinase 2 Homo sapiens 226-230 25135717-7 2014 The results demonstrated that icaritin induced cell cycle arrest at S phase, and down-regulated the expression levels of S regulatory proteins such as Cyclin A and CDK2. icaritin 30-38 cyclin dependent kinase 2 Homo sapiens 164-168 24865236-2 2014 SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7 and Cdk9 and has emerged in clinical trials. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 0-7 cyclin dependent kinase 2 Homo sapiens 47-51 24799199-7 2014 In addition, NAC pretreatment partly ameliorated OTA-induced S-phase arrest by preventing the down-regulation of cyclin A2, cyclin E1 and CDK2 expression in HEK-293 cells. Acetylcysteine 13-16 cyclin dependent kinase 2 Homo sapiens 138-142 25084614-9 2014 MK-1775 induced apoptosis in both AML cell lines and diagnostic blast samples, accompanied by decreased phosphorylation of CDK1 and CDK2 on Tyr-15 and increased DNA double-strand breaks (DSBs). adavosertib 0-7 cyclin dependent kinase 2 Homo sapiens 132-136 24889088-6 2014 Furthermore, flow cytometric cell cycle analysis revealed that germacrone induced G1 phase arrest, associated with an obvious decrease in the expression of cyclin D1 and CDK2 and an increased expression of p21. germacrone 63-73 cyclin dependent kinase 2 Homo sapiens 170-174 25084614-9 2014 MK-1775 induced apoptosis in both AML cell lines and diagnostic blast samples, accompanied by decreased phosphorylation of CDK1 and CDK2 on Tyr-15 and increased DNA double-strand breaks (DSBs). Tyrosine 140-143 cyclin dependent kinase 2 Homo sapiens 132-136 24909777-0 2014 Insights into the structural basis of 3,5-diaminoindazoles as CDK2 inhibitors: prediction of binding modes and potency by QM-MM interaction, MESP and MD simulation. 3,5-diaminoindazoles 38-58 cyclin dependent kinase 2 Homo sapiens 62-66 24978614-4 2014 We have found Kenpaullone, a potent CDK1, CDK2 and CDK5 inhibitor, as new enhancer for iTreg cell differentiation. kenpaullone 14-25 cyclin dependent kinase 2 Homo sapiens 42-46 24872417-5 2014 Furthermore, in contrast to Cdk1 and Cdk2, which are inhibited by phosphorylation at Tyr-15, the kinase activity of Cdk5 is reported to be stimulated when phosphorylated at Tyr-15 by Src family kinases or receptor-type tyrosine kinases. Tyrosine 85-88 cyclin dependent kinase 2 Homo sapiens 37-41 24978614-6 2014 Thus, we have demonstrated that CDK2 is the biological target of Kenpaullone and proven that CDK2 is a novel negative regulator of iTreg cell differentiation. kenpaullone 65-76 cyclin dependent kinase 2 Homo sapiens 32-36 24760952-5 2014 Quercetin-induced cell apoptosis was shown to involve p53 and p21 up-regulation, Cyclin D1, Cdk2, and Cdk7 down-regulation. Quercetin 0-9 cyclin dependent kinase 2 Homo sapiens 92-96 24935000-12 2014 CONCLUSION: It is concluded that non-response to everolimus is characterized by increased cdk2/cyclin A, driving RCC cells into the G2/M-phase. Everolimus 49-59 cyclin dependent kinase 2 Homo sapiens 90-94 24935000-13 2014 VPA hinders everolimus non-response by diminishing cdk2/cyclin A. Everolimus 12-22 cyclin dependent kinase 2 Homo sapiens 51-55 24935000-0 2014 HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in vitro by diminishing cdk2 and cyclin A. Everolimus 28-38 cyclin dependent kinase 2 Homo sapiens 98-102 24695376-2 2014 2-Undecylsulfonyl-DMNQ significantly inhibited PDGF-stimulated cell number and DNA synthesis, and arrested the PDGF-stimulated progression through G0/G1 to S phase of cell cycle supported by the suppression of pRb phosphorylation and cyclin D1/E, CDK2/4 and PCNA expressions. 2-undecylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone 0-22 cyclin dependent kinase 2 Homo sapiens 247-251 24760952-6 2014 These results suggested that the induction of G2/M arrest, apoptosis, and cell death by quercetin may associate with increased expression of p53 and p21, decrease of Cyclin D1, Cdk2, and Cdk7 levels, and generation of reactive oxygen species in cells. Quercetin 88-97 cyclin dependent kinase 2 Homo sapiens 177-181 24732362-1 2014 Phosphorylation of Thr(116) and Thr(226) on Orc2, one of the six subunits of the origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin and replication origins. Threonine 32-35 cyclin dependent kinase 2 Homo sapiens 127-131 24646031-3 2014 In many cases, downregulation of CDK activity by ATRA and vitamin D3 is a result of elevated p21- and p27-bound CDKs. Tretinoin 49-53 cyclin dependent kinase 2 Homo sapiens 112-116 24646031-3 2014 In many cases, downregulation of CDK activity by ATRA and vitamin D3 is a result of elevated p21- and p27-bound CDKs. Cholecalciferol 58-68 cyclin dependent kinase 2 Homo sapiens 112-116 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 59-63 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 76-80 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Cholecalciferol 9-19 cyclin dependent kinase 2 Homo sapiens 59-63 24646031-6 2014 ATRA and vitamin D3 can also downregulate expression of G1 CDKs, especially CDK2 and CDK6. Cholecalciferol 9-19 cyclin dependent kinase 2 Homo sapiens 76-80 24646031-9 2014 Finally, sharp reduction in c-Myc has been observed in several leukaemia cell lines treated with ATRA, which may regulate expression of CDKs and CKIs. Tretinoin 97-101 cyclin dependent kinase 2 Homo sapiens 136-140 24813092-8 2014 Two of the five tumors displayed significantly altered kinase activity in the TMZ resistant xenolines and network modeling indicated PKC, JAK1, PI3K, CDK2, and VEGFR as potential mediators of this resistance. Temozolomide 78-81 cyclin dependent kinase 2 Homo sapiens 150-154 24732362-1 2014 Phosphorylation of Thr(116) and Thr(226) on Orc2, one of the six subunits of the origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin and replication origins. Threonine 19-22 cyclin dependent kinase 2 Homo sapiens 127-131 24759790-0 2014 Phosphorylation of CDK2 on threonine 160 influences silencing of sex chromosome during male meiosis. Threonine 27-36 cyclin dependent kinase 2 Homo sapiens 19-23 24759790-4 2014 Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. Threonine 88-97 cyclin dependent kinase 2 Homo sapiens 48-52 24759790-4 2014 Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. Threonine 88-97 cyclin dependent kinase 2 Homo sapiens 66-70 24759790-4 2014 Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. gamma-h2ax 188-198 cyclin dependent kinase 2 Homo sapiens 48-52 24759790-4 2014 Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. gamma-h2ax 188-198 cyclin dependent kinase 2 Homo sapiens 66-70 24759790-6 2014 Furthermore, pachytene spermatocytes treated with mevastatin (an inhibitor of p-CDK2) showed overexpression of sex chromosome-linked genes. mevastatin 50-60 cyclin dependent kinase 2 Homo sapiens 80-84 24861464-6 2014 DYRK1A, CDK2, BMI-1 and Girdin, which are targets of miR-1246, miR-302a and miR-4448, were suppressed by treatment with SAHA and DZNep, leading to apoptosis, cell cycle arrest and reduced migration of AGS and HepG2 cells. 3-deazaneplanocin 129-134 cyclin dependent kinase 2 Homo sapiens 8-12 24847863-6 2014 Previously, we identified cyclin A-associated cyclin-dependent kinase 2 (Cdk2) as the principal kinase that was required for pemetrexed-induced S-phase arrest and apoptosis. Pemetrexed 125-135 cyclin dependent kinase 2 Homo sapiens 73-77 24847863-9 2014 Overall, our results indicate that, in contrast to its normal prosurvival role, the activated Akt plays a proapoptotic role in pemetrexed-mediated S-phase arrest and cell death through a mechanism that involves Cdk2/cyclin A activation. Pemetrexed 127-137 cyclin dependent kinase 2 Homo sapiens 211-215 24550143-0 2014 Curcumin suppresses proliferation of colon cancer cells by targeting CDK2. Curcumin 0-8 cyclin dependent kinase 2 Homo sapiens 69-73 24627094-3 2014 In TC-1 cells sequentially treated with bortezomib and celecoxib, apoptosis was induced through decreased expression of signal transducer and activator of transcription-3 (STAT3), cyclin D1 and cyclin-dependent kinase (CDK) 2, which are major regulators of the G0/G1 cell cycle checkpoint. Bortezomib 40-50 cyclin dependent kinase 2 Homo sapiens 194-225 24627094-3 2014 In TC-1 cells sequentially treated with bortezomib and celecoxib, apoptosis was induced through decreased expression of signal transducer and activator of transcription-3 (STAT3), cyclin D1 and cyclin-dependent kinase (CDK) 2, which are major regulators of the G0/G1 cell cycle checkpoint. Celecoxib 55-64 cyclin dependent kinase 2 Homo sapiens 194-225 24686014-1 2014 The docking studies on CDK2 and GSK-3beta inspired us to synthesis a series of indoline-2,3-dione hydrazones 10a-l. indoline-2,3-dione hydrazones 79-108 cyclin dependent kinase 2 Homo sapiens 23-27 24816095-6 2014 Sunitinib forms nine preserved bond paths corresponding to hydrogen bonds and also to the C-H O and C-H pi contacts common to the VEGRF2, CDK2, G2, KIT and IT kinases. Sunitinib 0-9 cyclin dependent kinase 2 Homo sapiens 142-146 22505597-7 2014 The combined treatment of FNQ with PP2 enhanced the cell cycle arrest and apoptosis and also led to the downregulation of Bcl-XL, Mcl-1, XIAP, cyclin A, cyclin B, CDK1, and CDK2 and upregulation of p27, Bax, and Bad. furano-1,2-naphthoquinone 26-29 cyclin dependent kinase 2 Homo sapiens 173-177 23846545-10 2014 BAY 11-7082 also induced S phase arrest through suppressing Cyclin A and CDK-2 expression. 3-(4-methylphenylsulfonyl)-2-propenenitrile 0-11 cyclin dependent kinase 2 Homo sapiens 73-78 24588135-1 2014 The fungus-derived compound cephalochromin, isolated from the fermented broth of Cosmospora vilior YMJ89051501, shows growth-inhibitory and apoptotic activity against human lung cancer A549 cells in a concentration-dependent manner with an IC50 value of 2.8 muM at 48 h. Cephalochromin induced cell cycle arrest at the G0/G1 phase through down-regulation of cyclin D1, cyclin E, Cdk 2, and Cdk 4 expressions. cephalochromin 28-42 cyclin dependent kinase 2 Homo sapiens 379-384 24550143-4 2014 Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Curcumin 112-120 cyclin dependent kinase 2 Homo sapiens 0-25 24550143-4 2014 Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Curcumin 112-120 cyclin dependent kinase 2 Homo sapiens 27-31 24550143-5 2014 Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Curcumin 89-97 cyclin dependent kinase 2 Homo sapiens 101-105 24550143-6 2014 Furthermore, curcumin induced G1 cell-cycle arrest, which is regulated by CDK2 in HCT116 cells. Curcumin 13-21 cyclin dependent kinase 2 Homo sapiens 74-78 24550143-7 2014 Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of retinoblastoma (Rb), a well-known CDK2 substrate, was reduced by curcumin. Curcumin 183-191 cyclin dependent kinase 2 Homo sapiens 152-156 24550143-10 2014 To determine whether CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. Curcumin 48-56 cyclin dependent kinase 2 Homo sapiens 21-25 24550143-13 2014 From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells. Curcumin 61-69 cyclin dependent kinase 2 Homo sapiens 34-38 24606123-1 2014 The progesterone receptor (PR) and its coactivators are direct targets of activated cyclin-dependent kinases (CDKs) in response to peptide growth factors, progesterone, and deregulation of cell cycle inhibitors. Progesterone 4-16 cyclin dependent kinase 2 Homo sapiens 110-114 24635079-8 2014 ATRA also induced G1 cell-cycle arrest, inhibited the expression of cyclin D1/cyclin-dependent kinase (CDK)4 and cyclinE/CDK2, and increased the expression of the cyclin-dependent kinase inhibitors p21 and p27. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 121-125 22431435-8 2014 Western blotting analysis indicated that quercetin induces the G0/G1 phase arrest via decreasing the levels of CDK2, cyclins E, and D proteins. Quercetin 41-50 cyclin dependent kinase 2 Homo sapiens 111-115 24606123-10 2014 Mutation of PR Ser345 to Ala (S345A) or inhibition of CDK2 activity using roscovitine disrupted PR/cyclin D1 interactions with DNA and blocked HSPB8 mRNA expression. Roscovitine 74-85 cyclin dependent kinase 2 Homo sapiens 54-58 24296733-2 2014 Artemisinin induced a G1 cell cycle arrest in cultured human Ishikawa endometrial cancer cells and downregulated cyclin-dependent kinase-2 (CDK2) and CDK4 transcript and protein levels. artemisinin 0-11 cyclin dependent kinase 2 Homo sapiens 113-138 24658119-1 2014 We previously showed that treating vascular endothelial cells with 3-methylcholanthrene (3MC) caused cell-cycle arrest in the Go/G1 phase; this resulted from the induction of p21 and p27 and a decreased level and activity of the cyclin-dependent kinase, Cdk2. Methylcholanthrene 67-87 cyclin dependent kinase 2 Homo sapiens 254-258 24658119-1 2014 We previously showed that treating vascular endothelial cells with 3-methylcholanthrene (3MC) caused cell-cycle arrest in the Go/G1 phase; this resulted from the induction of p21 and p27 and a decreased level and activity of the cyclin-dependent kinase, Cdk2. Methylcholanthrene 89-92 cyclin dependent kinase 2 Homo sapiens 254-258 24533688-7 2014 Meanwhile, the protein levels of CDK inhibitors p21(Waf1/Cip1) and p27(KIP1) also exhibited upregulation after garcinol treatments. garcinol 111-119 cyclin dependent kinase 2 Homo sapiens 33-36 24598942-5 2014 Further studies demonstrated that zardaverine induced G0/G1 phase cell cycle arrest of sensitive HCC cells through dysregulating cell cycle-associated proteins, including Cdk4, Cdk6, Cdk2, Cyclin A, Cyclin E, p21 and Rb. zardaverine 34-45 cyclin dependent kinase 2 Homo sapiens 183-187 24296733-2 2014 Artemisinin induced a G1 cell cycle arrest in cultured human Ishikawa endometrial cancer cells and downregulated cyclin-dependent kinase-2 (CDK2) and CDK4 transcript and protein levels. artemisinin 0-11 cyclin dependent kinase 2 Homo sapiens 140-144 24407240-4 2014 Chromatin immunoprecipitation showed that cyclin-dependent kinase 2 (CDK2) associated with the CCAAT box-containing region of PLK1 promoter in unstressed cells, whereas adriamycin (ADR) induced the recruitment of p21 with a concomitant reduction in the occupancy of CDK2 in this region. Doxorubicin 169-179 cyclin dependent kinase 2 Homo sapiens 266-270 27485571-4 2014 As a result, a detailed map of the hydrogen bonds (HBs) and hydrophobic interactions between the T-loop residues of CDK2 and the residues of cycA that are different among nonphosphorylated and phosphorylated complexes were described. Hydrogen 35-43 cyclin dependent kinase 2 Homo sapiens 116-120 24337632-7 2014 LY294002 induced cell cycle arrest at G0/G1 in SNU-449 and Mahlavu cells by decreasing expression of CDK2, CDK4, CycD1, CycD3, CycE, CycA and increasing expression of p21 and p27 as well; it also caused a decrease in the E2F1 transcriptional activity through declining phosphorylated Rb. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 0-8 cyclin dependent kinase 2 Homo sapiens 101-105 24870773-17 2014 Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. kappa-selenocarrageenan 89-92 cyclin dependent kinase 2 Homo sapiens 35-39 24304238-0 2014 8-Substituted O(6)-cyclohexylmethylguanine CDK2 inhibitors: using structure-based inhibitor design to optimize an alternative binding mode. 8-substituted o(6)-cyclohexylmethylguanine 0-42 cyclin dependent kinase 2 Homo sapiens 43-47 24304238-6 2014 By contrast, the corresponding 8-(2-methyl-3-sulfamoylphenyl)-purine derivative exhibited submicromolar CDK2-inhibitory activity by virtue of engineered additional interactions with Asp86 and Lys89 in the reversed binding mode, as confirmed by X-ray crystallography. 8-(2-methyl-3-sulfamoylphenyl)-purine 31-68 cyclin dependent kinase 2 Homo sapiens 104-108 24870773-17 2014 Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. kappa-selenocarrageenan 138-141 cyclin dependent kinase 2 Homo sapiens 35-39 24240190-7 2014 We also report that the differential profile of Rb phosphorylation may follow as a consequence of differences in the content of cyclin-dependent kinase 2 (CDK2) and the CDK4 phosphorylation inhibitor p15. Rubidium 48-50 cyclin dependent kinase 2 Homo sapiens 128-153 24332088-0 2014 Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor. quinoline 60-69 cyclin dependent kinase 2 Homo sapiens 35-39 24332088-1 2014 A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. Adenosine Triphosphate 162-165 cyclin dependent kinase 2 Homo sapiens 107-111 24240190-7 2014 We also report that the differential profile of Rb phosphorylation may follow as a consequence of differences in the content of cyclin-dependent kinase 2 (CDK2) and the CDK4 phosphorylation inhibitor p15. Rubidium 48-50 cyclin dependent kinase 2 Homo sapiens 155-159 24164195-9 2014 In addition, a structural comparison of shikimate kinase ATP-binding pocket with human cyclin-dependent kinase 2 (CDK2) is described. Adenosine Triphosphate 57-60 cyclin dependent kinase 2 Homo sapiens 87-112 24164195-9 2014 In addition, a structural comparison of shikimate kinase ATP-binding pocket with human cyclin-dependent kinase 2 (CDK2) is described. Adenosine Triphosphate 57-60 cyclin dependent kinase 2 Homo sapiens 114-118 25268087-11 2014 In addition, saikosaponin-d administration led to a significant up-regulation of p21 and down-regulation of CDK2 and cyclin D1. saikosaponin D 13-27 cyclin dependent kinase 2 Homo sapiens 108-112 25382189-4 2014 JM118 increased the phosphorylation of the cell cycle proteins CDK2 and CHK1 after 24 hr exposure. amminedichloro(cyclohexylamine)platinum(II) 0-5 cyclin dependent kinase 2 Homo sapiens 63-67 24370028-5 2013 The As2O3 induced the apoptosis of Namalwa cells in concentration-and time-dependent manner, downregulated the expression of the important driving genes of cell cycle including Cyclin E and CDK2 in mRNA and protein level, upregulated the expression of the important inhibiting gene of cell cycle-P21 in mRNA and protein level in concentration-dependent manner. Arsenic Trioxide 4-9 cyclin dependent kinase 2 Homo sapiens 190-194 25477962-0 2014 Assessment of the Potential of CDK2 Inhibitor NU6140 to Influence the Expression of Pluripotency Markers NANOG, OCT4, and SOX2 in 2102Ep and H9 Cells. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 46-52 cyclin dependent kinase 2 Homo sapiens 31-35 25477962-2 2014 In this study we investigated the effects of the small molecular agent NU6140 (inhibits CDK2 and cyclin A interaction) on human embryonic stem (hES) cells and embryonal carcinoma-derived (hEC) cells via the expression of transcription factors responsible for pluripotency. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 71-77 cyclin dependent kinase 2 Homo sapiens 88-92 24213303-6 2014 Western blot analysis revealed that sorafenib upregulated the expression of cyclin D1 and cyclin-dependent kinase 2 and downregulated the expression of BAX at this specific point. Sorafenib 36-45 cyclin dependent kinase 2 Homo sapiens 90-115 24099794-4 2013 COH-SR4 treatment caused the inhibition of GST activity and G0/G1 cell cycle arrest and inhibited the expression of cell cycle regulatory proteins CDK2, CDK4, cyclin A, cyclin B1, cyclin E1, and p27. 1,3-bis(3,5-dichlorophenyl)urea 0-7 cyclin dependent kinase 2 Homo sapiens 147-151 23401195-6 2013 Moreover, Fangchinoline also inhibited the kinase activities of CDK2, CDK4, and CDK6. fangchinoline 10-23 cyclin dependent kinase 2 Homo sapiens 64-68 24190517-6 2014 MHY412-induced sub-G1 phase arrest was associated with inhibition of cyclin, cyclin-dependent kinase 2 (CDK2) and p21 expression in MCF-7/Adr cells. mhy412 0-6 cyclin dependent kinase 2 Homo sapiens 77-102 24190517-6 2014 MHY412-induced sub-G1 phase arrest was associated with inhibition of cyclin, cyclin-dependent kinase 2 (CDK2) and p21 expression in MCF-7/Adr cells. mhy412 0-6 cyclin dependent kinase 2 Homo sapiens 104-108 25264561-5 2014 Magnolol inhibited the expression of cell cycle regulatory proteins including cyclins A, B1, D1, and E, as well as CDK2 and CDK4. magnolol 0-8 cyclin dependent kinase 2 Homo sapiens 115-119 24071597-6 2013 We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. icec-0782 13-22 cyclin dependent kinase 2 Homo sapiens 53-57 24007471-2 2013 Dinaciclib is a potent inhibitor of cyclin-dependent kinases (CDKs), which recently advanced to Phase III clinical trials for the treatment of leukemia. dinaciclib 0-10 cyclin dependent kinase 2 Homo sapiens 62-66 24007471-3 2013 We determined the crystal structure of dinaciclib in complex with CDK2 at 1.7 A resolution, revealing an elaborate network of binding interactions in the ATP site, which explains the extraordinary potency and selectivity of this inhibitor. dinaciclib 39-49 cyclin dependent kinase 2 Homo sapiens 66-70 24007471-3 2013 We determined the crystal structure of dinaciclib in complex with CDK2 at 1.7 A resolution, revealing an elaborate network of binding interactions in the ATP site, which explains the extraordinary potency and selectivity of this inhibitor. Adenosine Triphosphate 154-157 cyclin dependent kinase 2 Homo sapiens 66-70 24121337-0 2013 Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity. TEI I01800 80-90 cyclin dependent kinase 2 Homo sapiens 27-52 24121337-3 2013 TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 A resolution. TEI I01800 0-10 cyclin dependent kinase 2 Homo sapiens 132-157 24121337-3 2013 TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 A resolution. TEI I01800 0-10 cyclin dependent kinase 2 Homo sapiens 159-163 24121337-4 2013 Interestingly, the Gly-rich loop of CDK2 formed a beta-sheet that was different from that of MK2. Glycine 19-22 cyclin dependent kinase 2 Homo sapiens 36-40 24121337-6 2013 However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. tei 19-22 cyclin dependent kinase 2 Homo sapiens 13-17 24121337-6 2013 However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. tei 19-22 cyclin dependent kinase 2 Homo sapiens 39-43 24104967-5 2013 RESULTS: The active forms of Cdk4 and Cdk2 complexes in control tumour cells have a molecular size of ~140 kDa, which increased to ~290 kDa when inhibited following G1 checkpoint activation by DAP. (diaminocyclohexane)(diacetato)(dichloro)platinum 193-196 cyclin dependent kinase 2 Homo sapiens 38-42 24001891-0 2013 Polysaccharide from Phellinus linteus induces S-phase arrest in HepG2 cells by decreasing calreticulin expression and activating the P27kip1-cyclin A/D1/E-CDK2 pathway. Polysaccharides 0-14 cyclin dependent kinase 2 Homo sapiens 155-159 24060681-0 2013 Activation of P27kip1-cyclin D1/E-CDK2 pathway by polysaccharide from Phellinus linteus leads to S-phase arrest in HT-29 cells. Polysaccharides 50-64 cyclin dependent kinase 2 Homo sapiens 34-38 24119616-0 2013 Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells. Glucose 178-185 cyclin dependent kinase 2 Homo sapiens 155-159 24119616-11 2013 In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression under high glucose or normal glucose/H2O2 conditions. vsmcs 80-85 cyclin dependent kinase 2 Homo sapiens 230-234 24119616-11 2013 In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression under high glucose or normal glucose/H2O2 conditions. U 0126 125-130 cyclin dependent kinase 2 Homo sapiens 230-234 24119616-0 2013 Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells. Reactive Oxygen Species 45-68 cyclin dependent kinase 2 Homo sapiens 155-159 24119616-12 2013 CONCLUSIONS: These results demonstrate that the downstream effectors of Irf-1 are cyclin E/CDK2 during the high glucose-induced proliferation of VSMCs, whereas they are cyclin D1/CDK4 in normal glucose conditions. vsmcs 145-150 cyclin dependent kinase 2 Homo sapiens 91-95 24119616-9 2013 Treatment of VSMCs with antioxidants prevented the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose conditions. vsmcs 13-18 cyclin dependent kinase 2 Homo sapiens 134-138 24119616-10 2013 In contrast, under normal glucose conditions, H2O2 stimulation and Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2 expression and promoted cell cycle acceleration. Hydrogen Peroxide 46-50 cyclin dependent kinase 2 Homo sapiens 138-142 23707764-0 2013 CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth. isoangustone A 46-60 cyclin dependent kinase 2 Homo sapiens 0-4 23727278-1 2013 Molecular docking, free energy calculation and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 3,5-diaminoindazoles, imidazo(1,2-b)pyridazines and triazolo(1,5-a) pyridazines series of Cyclin-dependent kinase (CDK2) inhibitors. 3,5-diaminoindazoles 152-172 cyclin dependent kinase 2 Homo sapiens 267-271 23727278-1 2013 Molecular docking, free energy calculation and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 3,5-diaminoindazoles, imidazo(1,2-b)pyridazines and triazolo(1,5-a) pyridazines series of Cyclin-dependent kinase (CDK2) inhibitors. imidazo(1,2-b)pyridazines 174-199 cyclin dependent kinase 2 Homo sapiens 267-271 23727278-1 2013 Molecular docking, free energy calculation and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 3,5-diaminoindazoles, imidazo(1,2-b)pyridazines and triazolo(1,5-a) pyridazines series of Cyclin-dependent kinase (CDK2) inhibitors. triazolo(1,5-a) pyridazines 204-231 cyclin dependent kinase 2 Homo sapiens 267-271 23933045-0 2013 Synthesis, biological evaluation and molecular docking studies of pyrazole derivatives coupling with a thiourea moiety as novel CDKs inhibitors. pyrazole 66-74 cyclin dependent kinase 2 Homo sapiens 128-132 23933045-0 2013 Synthesis, biological evaluation and molecular docking studies of pyrazole derivatives coupling with a thiourea moiety as novel CDKs inhibitors. Thiourea 103-111 cyclin dependent kinase 2 Homo sapiens 128-132 23933045-1 2013 It was discovered that a number of cyclin dependent kinase inhibitors containing the pyrazole core structure exhibited high inhibitory potency against broad-range CDKs and corresponding anti-proliferative activities. pyrazole 85-93 cyclin dependent kinase 2 Homo sapiens 163-167 23933045-2 2013 This information guided us to design and synthesize a series of 1,3-diphenyl-N-(phenylcarbamothioyl)-1H-pyrazole-4-carboxamide derivatives (5a-10d), and evaluate their biological activities as CDKs inhibitors. 1,3-diphenyl-n-(phenylcarbamothioyl)-1h-pyrazole-4-carboxamide 64-126 cyclin dependent kinase 2 Homo sapiens 193-197 23941641-3 2013 The comparative molecular similarity indices analysis (CoMSIA) model constructed based on a set of 3-aminopyrazole derivatives as CDK2 inhibitors gave statistically significant results (q (2) = 0.700; r (2) = 0.982). 3-aminopyrazole 99-114 cyclin dependent kinase 2 Homo sapiens 130-134 23994326-0 2013 6-Cyclohexylmethoxy-5-(cyano-NNO-azoxy)pyrimidine-4-amine: a new scaffold endowed with potent CDK2 inhibitory activity. 6-cyclohexylmethoxy-5-(cyano-nno-azoxy)pyrimidine-4-amine 0-57 cyclin dependent kinase 2 Homo sapiens 94-98 23994326-1 2013 Substitution of the cyano-NNO-azoxy moiety (NC-N=(O)N-) for the nitroso group in NU6027, a potent and selective CDK2 inhibitor, affords a compound with slightly improved potency and comparable selectivity profile. cyano-nno-azoxy 20-35 cyclin dependent kinase 2 Homo sapiens 112-116 23994326-1 2013 Substitution of the cyano-NNO-azoxy moiety (NC-N=(O)N-) for the nitroso group in NU6027, a potent and selective CDK2 inhibitor, affords a compound with slightly improved potency and comparable selectivity profile. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 81-87 cyclin dependent kinase 2 Homo sapiens 112-116 23994326-3 2013 The introduction of aminosulfonylphenyl substituents on the 2-amino group of the pyrimidine increased the CDK2 inhibitory potency by two orders of magnitude, while maintaining the same degree of selectivity. pyrimidine 81-91 cyclin dependent kinase 2 Homo sapiens 106-110 23707764-7 2013 Further analysis using recombinant proteins and immunoprecipitated cell lysates determined that IAA exerts suppressive effects against CDK2 and mTOR kinase activity by direct binding with both proteins. isoangustone A 96-99 cyclin dependent kinase 2 Homo sapiens 135-139 23046590-6 2013 The amine coating also increased procollagen type I (pro-COL1) expression and increased phosphorylation signals, such as focal adhesion kinase (FAK) and cytosolic Src, as well as enhanced ERK/CDK2 signaling. Amines 4-9 cyclin dependent kinase 2 Homo sapiens 192-196 24058495-0 2013 Molecular basis of differential selectivity of cyclobutyl-substituted imidazole inhibitors against CDKs: insights for rational drug design. cyclobutyl-substituted imidazole 47-79 cyclin dependent kinase 2 Homo sapiens 99-103 24058495-6 2013 Recently, cis-substituted cyclobutyl-4-aminoimidazole inhibitors have been identified as potent CDK5 inhibitors that gave up to 30-fold selectivity over CDK2. cis-substituted cyclobutyl-4-aminoimidazole 10-53 cyclin dependent kinase 2 Homo sapiens 153-157 24058495-8 2013 To understand the molecular basis of higher potency and selectivity of these inhibitors, here, we present molecular dynamics simulation results of CDK5/p25 and CDK2/CyclinE complexed with a series of cyclobutyl-substituted imidazole inhibitors and roscovitine. cyclobutyl-substituted imidazole 200-232 cyclin dependent kinase 2 Homo sapiens 160-164 24058495-8 2013 To understand the molecular basis of higher potency and selectivity of these inhibitors, here, we present molecular dynamics simulation results of CDK5/p25 and CDK2/CyclinE complexed with a series of cyclobutyl-substituted imidazole inhibitors and roscovitine. Roscovitine 248-259 cyclin dependent kinase 2 Homo sapiens 160-164 24018901-6 2013 Hippuristanol also reduced the expression of cyclin D2, CDK2, CDK4, CDK6 and prosurvival XIAP and Mcl-1 proteins. hippuristanol 0-13 cyclin dependent kinase 2 Homo sapiens 56-60 23888052-9 2013 Pulldown and in vitro kinase assay results indicated that compound 69407 directly binds with Cdk2 and Cdk4 in an ATP-independent manner and inhibited their kinase activities. Adenosine Triphosphate 113-116 cyclin dependent kinase 2 Homo sapiens 93-97 23888052-12 2013 Overall results indicated that compound 69407 is an ATP-noncompetitive cyclin-dependent kinase inhibitor with anti-tumor effects, which acts by binding inside the Cdk2 allosteric pocket. Adenosine Triphosphate 52-55 cyclin dependent kinase 2 Homo sapiens 163-167 23864105-0 2013 An in silico exploration of the interaction mechanism of pyrazolo[1,5-a]pyrimidine type CDK2 inhibitors. pyrazolo(1,5-a)pyrimidine 57-82 cyclin dependent kinase 2 Homo sapiens 88-92 25337553-9 2013 Kaempferol induced G1 cell cycle arrest within 6 h and G2/M arrest at 12 h. Kaempferol inhibited the activity of CDK2 and CDK4 as well as the protein expression of CDK2, CDK4, cyclins D1, cyclin E, and cyclin A, and suppressed the phosphorylation of retinoblastoma protein. kaempferol 0-10 cyclin dependent kinase 2 Homo sapiens 113-117 25337553-9 2013 Kaempferol induced G1 cell cycle arrest within 6 h and G2/M arrest at 12 h. Kaempferol inhibited the activity of CDK2 and CDK4 as well as the protein expression of CDK2, CDK4, cyclins D1, cyclin E, and cyclin A, and suppressed the phosphorylation of retinoblastoma protein. kaempferol 0-10 cyclin dependent kinase 2 Homo sapiens 164-168 25337553-9 2013 Kaempferol induced G1 cell cycle arrest within 6 h and G2/M arrest at 12 h. Kaempferol inhibited the activity of CDK2 and CDK4 as well as the protein expression of CDK2, CDK4, cyclins D1, cyclin E, and cyclin A, and suppressed the phosphorylation of retinoblastoma protein. kaempferol 76-86 cyclin dependent kinase 2 Homo sapiens 113-117 25337553-9 2013 Kaempferol induced G1 cell cycle arrest within 6 h and G2/M arrest at 12 h. Kaempferol inhibited the activity of CDK2 and CDK4 as well as the protein expression of CDK2, CDK4, cyclins D1, cyclin E, and cyclin A, and suppressed the phosphorylation of retinoblastoma protein. kaempferol 76-86 cyclin dependent kinase 2 Homo sapiens 164-168 25337553-11 2013 CONCLUSIONS: The present results indicate that kaempferol induces G1 and G2/M cell cycle arrest by inhibiting the activity of CDK2, CDK4, and Cdc2. kaempferol 47-57 cyclin dependent kinase 2 Homo sapiens 126-130 23728955-1 2013 On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. indole 86-92 cyclin dependent kinase 2 Homo sapiens 80-84 23728955-1 2013 On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. Benzopyrans 97-105 cyclin dependent kinase 2 Homo sapiens 80-84 23864105-3 2013 In the present work, a total of 111 pyrazolo[1,5-a]pyrimidines (PHTPPs) as CDK2/cyclin A inhibitors were studied to conduct three-dimensional quantitative structure-activity (3D-QSAR) analyses. pyrazolo(1,5-a)pyrimidine 36-62 cyclin dependent kinase 2 Homo sapiens 75-79 23864105-3 2013 In the present work, a total of 111 pyrazolo[1,5-a]pyrimidines (PHTPPs) as CDK2/cyclin A inhibitors were studied to conduct three-dimensional quantitative structure-activity (3D-QSAR) analyses. phtpps 64-70 cyclin dependent kinase 2 Homo sapiens 75-79 23864105-7 2013 Comparative studies indicate that PHTPP derivatives fit well within the ATP binding cleft in CDK2, with the core heterocyclic ring overlapping significantly with the adenine group of ATP despite a small deflection. PHTPP 34-39 cyclin dependent kinase 2 Homo sapiens 93-97 23864105-7 2013 Comparative studies indicate that PHTPP derivatives fit well within the ATP binding cleft in CDK2, with the core heterocyclic ring overlapping significantly with the adenine group of ATP despite a small deflection. Adenosine Triphosphate 72-75 cyclin dependent kinase 2 Homo sapiens 93-97 23864105-7 2013 Comparative studies indicate that PHTPP derivatives fit well within the ATP binding cleft in CDK2, with the core heterocyclic ring overlapping significantly with the adenine group of ATP despite a small deflection. Adenine 166-173 cyclin dependent kinase 2 Homo sapiens 93-97 23864105-7 2013 Comparative studies indicate that PHTPP derivatives fit well within the ATP binding cleft in CDK2, with the core heterocyclic ring overlapping significantly with the adenine group of ATP despite a small deflection. Adenosine Triphosphate 183-186 cyclin dependent kinase 2 Homo sapiens 93-97 23864105-9 2013 It is anticipated that the binding mechanism and structural features of PHTPP inhibitors studied in the present work will benefit the discovery of more potent CDK2 inhibitors, and the valid pyrazolo[1,5-a]pyrimidine-7-N-yl inhibitors will soon emerge from the large number of screening programmes to enter in clinical studies. PHTPP 72-77 cyclin dependent kinase 2 Homo sapiens 159-163 23522452-9 2013 The anti-proliferative effect of XRT/RSV correlated with decreased expression of pro-proliferative molecule cyclin B, cyclin D, cdk2 and cdk4. xrt 33-36 cyclin dependent kinase 2 Homo sapiens 128-132 23829517-4 2013 In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety. 6-heterobiarylmethylamino 119-144 cyclin dependent kinase 2 Homo sapiens 47-51 23829517-4 2013 In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety. purine 165-171 cyclin dependent kinase 2 Homo sapiens 47-51 23853094-4 2013 The primary structure of Foxp3 contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr-Pro) within the N-terminal repressor domain, and we show that CDK2 can partner with cyclin E to phosphorylate Foxp3 at these sites. Serine 83-86 cyclin dependent kinase 2 Homo sapiens 153-157 23853094-4 2013 The primary structure of Foxp3 contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr-Pro) within the N-terminal repressor domain, and we show that CDK2 can partner with cyclin E to phosphorylate Foxp3 at these sites. Threonine 87-90 cyclin dependent kinase 2 Homo sapiens 153-157 23853094-4 2013 The primary structure of Foxp3 contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr-Pro) within the N-terminal repressor domain, and we show that CDK2 can partner with cyclin E to phosphorylate Foxp3 at these sites. Proline 91-94 cyclin dependent kinase 2 Homo sapiens 153-157 23853094-5 2013 Consistent with our previous demonstration that CDK2 negatively regulates Treg function, we find that mutation of the serine or threonine at each CDK motif to alanine (S/T A) results in enhanced Foxp3 protein stability in CD4(+) T cells. treg 74-78 cyclin dependent kinase 2 Homo sapiens 48-52 23853094-5 2013 Consistent with our previous demonstration that CDK2 negatively regulates Treg function, we find that mutation of the serine or threonine at each CDK motif to alanine (S/T A) results in enhanced Foxp3 protein stability in CD4(+) T cells. Serine 118-124 cyclin dependent kinase 2 Homo sapiens 48-52 23853094-5 2013 Consistent with our previous demonstration that CDK2 negatively regulates Treg function, we find that mutation of the serine or threonine at each CDK motif to alanine (S/T A) results in enhanced Foxp3 protein stability in CD4(+) T cells. Alanine 159-166 cyclin dependent kinase 2 Homo sapiens 48-52 23522452-9 2013 The anti-proliferative effect of XRT/RSV correlated with decreased expression of pro-proliferative molecule cyclin B, cyclin D, cdk2 and cdk4. Resveratrol 37-40 cyclin dependent kinase 2 Homo sapiens 128-132 23745024-3 2013 Real time polymerase chain reaction and Western blotting were used to observe expression changes in p21, p53, Bax, Bcl-2, CDK2, and CyclinD1 in gastric cancer cells exposed to TSA. trichostatin A 176-179 cyclin dependent kinase 2 Homo sapiens 122-126 23628508-7 2013 Furthermore, aspidin BB provoked S phase arrest in HO-8910 cells with up-regulation of pRb, E2F1, CDK2, cyclin E and cyclin A proteins. aspidin BB 13-23 cyclin dependent kinase 2 Homo sapiens 98-102 23425217-11 2013 These effects were caused by paeonol suppression of phosphorylation of cycle protein cdc2 and of CDK2. paeonol 29-36 cyclin dependent kinase 2 Homo sapiens 97-101 23685145-5 2013 Consistent with this model, C-terminal PP1c phosphorylation by cdk2-cyclinA was masked by TIMAP, and PP1c bound TIMAP when the active site was occupied by the inhibitor microcystin. microcystin 169-180 cyclin dependent kinase 2 Homo sapiens 63-67 23597922-6 2013 Our research establishes that PKR activation in VSMC leads to a G1 arrest brought about by an inhibition of cyclin-dependent kinase 2 (Cdk2) activity by p27(kip1). vsmc 48-52 cyclin dependent kinase 2 Homo sapiens 108-133 23597922-6 2013 Our research establishes that PKR activation in VSMC leads to a G1 arrest brought about by an inhibition of cyclin-dependent kinase 2 (Cdk2) activity by p27(kip1). vsmc 48-52 cyclin dependent kinase 2 Homo sapiens 135-139 23300027-0 2013 Predicting the impact of single-nucleotide polymorphisms in CDK2-flavopiridol complex by molecular dynamics analysis. alvocidib 65-77 cyclin dependent kinase 2 Homo sapiens 60-64 23300027-2 2013 Flavopiridol is a flavonoid derived from an indigenous plant act as a potent antitumor drug showing increased inhibitory activity toward CDK2. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 137-141 23300027-2 2013 Flavopiridol is a flavonoid derived from an indigenous plant act as a potent antitumor drug showing increased inhibitory activity toward CDK2. Flavonoids 18-27 cyclin dependent kinase 2 Homo sapiens 137-141 23300027-7 2013 Occurrence of these variations seriously affected the normal binding capacity of flavopiridol with CDK2. alvocidib 81-93 cyclin dependent kinase 2 Homo sapiens 99-103 23300027-9 2013 Notably, we noticed the decrease in number of hydrogen bonds between CDK2 and flavopiridol mutant complexes in the whole dynamic period. Hydrogen 46-54 cyclin dependent kinase 2 Homo sapiens 69-73 23300027-9 2013 Notably, we noticed the decrease in number of hydrogen bonds between CDK2 and flavopiridol mutant complexes in the whole dynamic period. alvocidib 78-90 cyclin dependent kinase 2 Homo sapiens 69-73 23594796-7 2013 Moreover, spliceostatin A, a natural SF3b inhibitor, markedly inhibited P27 expression by disrupting its pre-mRNA splicing and reduced CDK2/Cyclin E expression. spliceostatin A 10-25 cyclin dependent kinase 2 Homo sapiens 135-139 23497867-2 2013 The results show that regarding cell cycle-related proteins, three types of polysaccharides significantly enhance the expression of p27(Kip) in HepG2 and Bel-7404 cells, while suppressing the activity of cyclin D1/CDK4 and/or cyclin E/CDK2. Polysaccharides 76-91 cyclin dependent kinase 2 Homo sapiens 235-239 23799090-5 2013 Dehydrocostus lactone significantly inhibited cell proliferation, arrested the cells at the G2/M interface and caused a decrease in the expression of the cyclin-dependent kinase CDK2 and the cyclin-dependent kinase inhibitor p27(Kip1). Lactones 14-21 cyclin dependent kinase 2 Homo sapiens 178-182 23745024-7 2013 p21, p53 and Bax gene expression levels in AGS cells were increased with TSA treatment duration; Bcl-2, CDK2, and CyclinD1 gene expression levels were decreased with TSA treatment duration. trichostatin A 166-169 cyclin dependent kinase 2 Homo sapiens 104-108 23525646-10 2013 In the HaCaT epithelial cells, arecoline downregulated expression of the G1/S phase regulatory proteins cyclin D1, CDK4, CDK2, E2F1 as determined by reverse transcription-PCR analysis and western blotting. Arecoline 31-40 cyclin dependent kinase 2 Homo sapiens 121-125 25337543-9 2013 Urushiol induced cytostatic cell growth inhibition via upregulation of the cyclin-dependent kinase inhibitors, p21 (WAF1/CIP1) and p27 (KIP1) proteins and down-regulation of cyclin-dependent kinase 2 and 4 proteins in a p53-independent manner. urushiol 0-8 cyclin dependent kinase 2 Homo sapiens 174-205 23582790-4 2013 The mechanism was at least partially due to DHA induced apoptosis by upregulating the expression of Bax, downregulating Bcl-2, Bcl-xL and Procaspase-3, and increasing caspase-9 activation, induced cell cycle arrest by downregulating cyclin E, CDK2 and CDK4. artenimol 44-47 cyclin dependent kinase 2 Homo sapiens 243-247 23600925-2 2013 We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. Thiazole-2,4-diamine 45-60 cyclin dependent kinase 2 Homo sapiens 75-79 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. Roscovitine 10-21 cyclin dependent kinase 2 Homo sapiens 39-43 23446853-5 2013 Importantly, we demonstrated that Aurora-A kinase-induced centrosome amplification was mediated by Cdk2 kinase since molecular inhibition of Cdk2 activity by SU9516 suppressed Aurora-A centrosomal localization and consequent centrosome amplification. SU 9516 158-164 cyclin dependent kinase 2 Homo sapiens 99-103 23446853-5 2013 Importantly, we demonstrated that Aurora-A kinase-induced centrosome amplification was mediated by Cdk2 kinase since molecular inhibition of Cdk2 activity by SU9516 suppressed Aurora-A centrosomal localization and consequent centrosome amplification. SU 9516 158-164 cyclin dependent kinase 2 Homo sapiens 141-145 24010301-9 2013 CONCLUSION: Curcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1. curcumol 12-20 cyclin dependent kinase 2 Homo sapiens 194-198 23535330-1 2013 Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. 2-aminothiazole-4-carboxamide 36-65 cyclin dependent kinase 2 Homo sapiens 299-303 23462184-6 2013 This results in insufficient p21 to inhibit CDK2, leading to high CDK4 and CDK2 kinase activity upon doxorubicin treatment. Doxorubicin 101-112 cyclin dependent kinase 2 Homo sapiens 44-48 23462184-6 2013 This results in insufficient p21 to inhibit CDK2, leading to high CDK4 and CDK2 kinase activity upon doxorubicin treatment. Doxorubicin 101-112 cyclin dependent kinase 2 Homo sapiens 75-79 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. Roscovitine 10-21 cyclin dependent kinase 2 Homo sapiens 71-75 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. Roscovitine 10-21 cyclin dependent kinase 2 Homo sapiens 89-93 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. saos 151-155 cyclin dependent kinase 2 Homo sapiens 39-43 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. saos 151-155 cyclin dependent kinase 2 Homo sapiens 71-75 23042366-5 2013 Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. saos 151-155 cyclin dependent kinase 2 Homo sapiens 89-93 23341188-4 2013 Quantitative real-time reverse transcriptase-polymerase chain reaction and Western blotting analyses showed that the two TFA increased the mRNA and protein expression levels of PCNA, CDK2 and Cyclin E in HUVSMC. Trans Fatty Acids 121-124 cyclin dependent kinase 2 Homo sapiens 183-187 23341188-6 2013 These results suggested that linolelaidic acid exhibited a stronger proliferative effect on HUVSMC than elaidic acid, and regulation of CDK2 and Cyclin E may be important for the effect of the TFA on atherosclerosis. Trans Fatty Acids 193-196 cyclin dependent kinase 2 Homo sapiens 136-140 23157414-0 2013 Quantum mechanical scoring: structural and energetic insights into cyclin-dependent kinase 2 inhibition by pyrazolo[1,5-a]pyrimidines. pyrazolo(1,5-a)pyrimidine 107-133 cyclin dependent kinase 2 Homo sapiens 67-92 23180436-5 2013 Sunitinib induced G1 phase arrest associated with decreased cyclin D1, cyclin D3, and cyclin-dependent kinase (Cdk)2 and increased p27(Kip1), pRb1, and p130/Rb2 expression and phosphorylated activation of protein kinase C alpha and beta (PKCalpha/beta). Sunitinib 0-9 cyclin dependent kinase 2 Homo sapiens 111-116 23530650-6 2013 Western blotting showed that 75 muM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. allyl sulfide 39-42 cyclin dependent kinase 2 Homo sapiens 169-173 23305945-5 2013 We observed in neurons differentiated from both hiPS cell lines that Abeta induced toxicity correlated with cell cycle re-entry and was inhibited by pharmacological inhibitors or shRNAs against Cyclin-dependent kinase 2 (Cdk2). UNII-042A8N37WH 69-74 cyclin dependent kinase 2 Homo sapiens 194-219 23305945-5 2013 We observed in neurons differentiated from both hiPS cell lines that Abeta induced toxicity correlated with cell cycle re-entry and was inhibited by pharmacological inhibitors or shRNAs against Cyclin-dependent kinase 2 (Cdk2). UNII-042A8N37WH 69-74 cyclin dependent kinase 2 Homo sapiens 221-225 23254306-13 2013 However, simultaneous variation of CDK2 and CKIs produces a dramatic reduction of damage cells passing the G1/S with CDK2&p27 combination causing senescence in almost all damaged cells. Adenosine Monophosphate 122-125 cyclin dependent kinase 2 Homo sapiens 35-39 23254306-13 2013 However, simultaneous variation of CDK2 and CKIs produces a dramatic reduction of damage cells passing the G1/S with CDK2&p27 combination causing senescence in almost all damaged cells. Adenosine Monophosphate 122-125 cyclin dependent kinase 2 Homo sapiens 117-121 23254306-15 2013 A review of the crucial protein complexes revealed that the concentration of active CycE/CDK2-p that controls cell cycle arrest provides support for the above findings with CycE/CDK2-p undergoing the largest reduction (over 100%) under the combined CDK2&CKI conditions leading to the arrest of most of the damaged cells. Adenosine Monophosphate 254-257 cyclin dependent kinase 2 Homo sapiens 89-93 23254306-15 2013 A review of the crucial protein complexes revealed that the concentration of active CycE/CDK2-p that controls cell cycle arrest provides support for the above findings with CycE/CDK2-p undergoing the largest reduction (over 100%) under the combined CDK2&CKI conditions leading to the arrest of most of the damaged cells. Adenosine Monophosphate 254-257 cyclin dependent kinase 2 Homo sapiens 178-182 23254306-15 2013 A review of the crucial protein complexes revealed that the concentration of active CycE/CDK2-p that controls cell cycle arrest provides support for the above findings with CycE/CDK2-p undergoing the largest reduction (over 100%) under the combined CDK2&CKI conditions leading to the arrest of most of the damaged cells. Adenosine Monophosphate 254-257 cyclin dependent kinase 2 Homo sapiens 178-182 23086460-4 2013 For example, in silico targeting of ATP-competitive inhibitors of CDKs is of special interest. Adenosine Triphosphate 36-39 cyclin dependent kinase 2 Homo sapiens 66-70 23344197-6 2013 Cyclin-dependent kinase (cdk) 2 and cdc2 was also decreased after chamaejasmine treatment. chamaejasmine 66-79 cyclin dependent kinase 2 Homo sapiens 0-31 23177257-5 2013 To elucidate the possible interaction between naringenin derivatives and CDK2, in silico docking study was performed. naringenin 46-56 cyclin dependent kinase 2 Homo sapiens 73-77 23735868-13 2013 Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3beta (ser9) and increased the expression of p27(Kip1) and p21(WAF1/CIP1). sodium bisulfide 18-22 cyclin dependent kinase 2 Homo sapiens 59-63 22973961-9 2013 No direct drug interaction was detected by LC-MS/MS measurement, while lysates from A549 and H1975 cells exposed to erlotinib+sorafenib showed a significant inhibition in the phosphorylation of 16 overlapping peptides, including sites from RAF, VEGFR2, PDGFR, CDK2 and SRC, suggesting new markers to identify NSCLC patients who are likely to respond to this treatment. Erlotinib Hydrochloride 116-125 cyclin dependent kinase 2 Homo sapiens 260-264 22973961-9 2013 No direct drug interaction was detected by LC-MS/MS measurement, while lysates from A549 and H1975 cells exposed to erlotinib+sorafenib showed a significant inhibition in the phosphorylation of 16 overlapping peptides, including sites from RAF, VEGFR2, PDGFR, CDK2 and SRC, suggesting new markers to identify NSCLC patients who are likely to respond to this treatment. Sorafenib 126-135 cyclin dependent kinase 2 Homo sapiens 260-264 23266736-5 2013 Rather, combined treatment with subeffective doses of gamma-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. plastochromanol 8 54-71 cyclin dependent kinase 2 Homo sapiens 169-173 23266736-5 2013 Rather, combined treatment with subeffective doses of gamma-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. sesamin 76-83 cyclin dependent kinase 2 Homo sapiens 169-173 22770608-4 2013 For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. 2-(hydroxyalkylamino) 19-40 cyclin dependent kinase 2 Homo sapiens 97-101 23321641-9 2013 Cells with overactive Cdk2 fail to arrest after mitotic slippage in the presence of paclitaxel or cytokinesis failure during treatment with cytochalasin-B, generating 8N populations. Paclitaxel 84-94 cyclin dependent kinase 2 Homo sapiens 22-26 23321641-9 2013 Cells with overactive Cdk2 fail to arrest after mitotic slippage in the presence of paclitaxel or cytokinesis failure during treatment with cytochalasin-B, generating 8N populations. Cytochalasin B 140-154 cyclin dependent kinase 2 Homo sapiens 22-26 23252711-5 2013 Finally, on the basis of 11 cocrystal structures bound to CDK9/cyclin T or CDK2/cyclin A, we conclude that selective inhibition of CDK9/cyclin T by members of the 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile series results from the relative malleability of the CDK9 active site rather than from the formation of specific polar contacts. 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile 163-220 cyclin dependent kinase 2 Homo sapiens 75-79 23184662-5 2013 We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. Serine 138-144 cyclin dependent kinase 2 Homo sapiens 115-119 23607100-8 2013 The inhibitory effect of GW501516 on HPASMCs was associated with decreased expression of cyclin D1, cyclin D3, CDK2, and CDK4 as well as increased expression of the cell cycle inhibitory genes G0S2 and P27(kip1). GW 501516 25-33 cyclin dependent kinase 2 Homo sapiens 111-115 22926267-0 2013 A flexible-protein molecular docking study of the binding of ruthenium complex compounds to PIM1, GSK-3beta, and CDK2/Cyclin A protein kinases. Ruthenium complex 61-78 cyclin dependent kinase 2 Homo sapiens 113-117 22926267-1 2013 We employ ensemble docking simulations to characterize the interactions of two enantiomeric forms of a Ru-complex compound (1-R and 1-S) with three protein kinases, namely PIM1, GSK-3beta, and CDK2/cyclin A. Ruthenium 103-105 cyclin dependent kinase 2 Homo sapiens 193-197 22926267-1 2013 We employ ensemble docking simulations to characterize the interactions of two enantiomeric forms of a Ru-complex compound (1-R and 1-S) with three protein kinases, namely PIM1, GSK-3beta, and CDK2/cyclin A. 1-r 124-127 cyclin dependent kinase 2 Homo sapiens 193-197 22926267-1 2013 We employ ensemble docking simulations to characterize the interactions of two enantiomeric forms of a Ru-complex compound (1-R and 1-S) with three protein kinases, namely PIM1, GSK-3beta, and CDK2/cyclin A. 1-s 132-135 cyclin dependent kinase 2 Homo sapiens 193-197 23320119-6 2013 On the other hand, zebularine treatment downregulated CDK2 and the phosphorylation of retinoblastoma protein (Rb), and upregulated p21(WAF/CIP1) and p53. pyrimidin-2-one beta-ribofuranoside 19-29 cyclin dependent kinase 2 Homo sapiens 54-58 23437375-5 2013 Repression of CDK2 activity with the chemical inhibitor roscovitine or with specific small interfering RNAs significantly decreased pRb phosphorylation, with concomitant repression of viral replication. Roscovitine 56-67 cyclin dependent kinase 2 Homo sapiens 14-18 23192020-6 2012 Comparison with the structural homolog cyclin-dependent kinase 2 reveals differences in the way that the ATP binding to the protein is mediated by magnesium. Adenosine Triphosphate 105-108 cyclin dependent kinase 2 Homo sapiens 39-64 23192020-6 2012 Comparison with the structural homolog cyclin-dependent kinase 2 reveals differences in the way that the ATP binding to the protein is mediated by magnesium. Magnesium 147-156 cyclin dependent kinase 2 Homo sapiens 39-64 22526834-8 2012 In addition, pyrone 9 not only increased the p27 level but also enhanced its binding to with CDK2, CDK4 and CDK6 which resulted in the reduction of CDK2-, CDK4- and CDK6-associated kinase activities. Pyrones 13-19 cyclin dependent kinase 2 Homo sapiens 93-97 23079520-5 2012 In addition, KYS05047 increased the protein level of p27(KIP1) and suppressed the kinase activities of Cdk2 and Cdk4. 4-(benzylcarbamoylmethyl)-2-(biphenyl-4-ylamino)-3-(5-tert-butyloxycarbamoyl-1-pentyl)-3,4-dihydroquinazoline 13-21 cyclin dependent kinase 2 Homo sapiens 103-107 23053255-1 2012 PURPOSE: Dinaciclib, a selective inhibitor of cyclin-dependent kinase (CDK) 1, CDK2, CDK5, and CDK9, is metabolized via CYP3A4. dinaciclib 9-19 cyclin dependent kinase 2 Homo sapiens 79-83 22526834-8 2012 In addition, pyrone 9 not only increased the p27 level but also enhanced its binding to with CDK2, CDK4 and CDK6 which resulted in the reduction of CDK2-, CDK4- and CDK6-associated kinase activities. Pyrones 13-19 cyclin dependent kinase 2 Homo sapiens 148-152 23096116-4 2012 Here, we show that the ATP non-competitive CDK2/cyclin A inhibitor NBI1 sensitizes erlotinib-resistant tumor cells to the combination treatment (co-treatment) for apoptosis-mediated cell death. Adenosine Triphosphate 23-26 cyclin dependent kinase 2 Homo sapiens 43-47 22886373-5 2012 Interestingly, cell cycle analysis by flow cytometry and protein expression analysis by western blotting revealed that low dose of Cr(VI) (4 uM) exposure induced S phase cell cycle arrest with decreased mediator of replication checkpoint 1 (Mrc1) and cyclin-dependent kinase 2 (CDK2), while higher doses of Cr(VI) (16, 32 uM) exposure resulted in G2/M phase arrest with decreased budding uninhibited by benzimidazoles-related 1 (BubR1) and cell division cycle 25 (CDC25). Chromium 131-133 cyclin dependent kinase 2 Homo sapiens 251-276 22886373-5 2012 Interestingly, cell cycle analysis by flow cytometry and protein expression analysis by western blotting revealed that low dose of Cr(VI) (4 uM) exposure induced S phase cell cycle arrest with decreased mediator of replication checkpoint 1 (Mrc1) and cyclin-dependent kinase 2 (CDK2), while higher doses of Cr(VI) (16, 32 uM) exposure resulted in G2/M phase arrest with decreased budding uninhibited by benzimidazoles-related 1 (BubR1) and cell division cycle 25 (CDC25). Chromium 131-133 cyclin dependent kinase 2 Homo sapiens 278-282 22796189-6 2012 Similar to other CDKs, PCTAIRE-1 requires a proline residue immediately C-terminal to the phosphoacceptor site (+1) for optimal activity. Proline 44-51 cyclin dependent kinase 2 Homo sapiens 17-21 23037896-1 2012 In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. indolobenzazepines 40-58 cyclin dependent kinase 2 Homo sapiens 108-112 23037896-1 2012 In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. paullone 60-69 cyclin dependent kinase 2 Homo sapiens 108-112 23247390-3 2012 In this study, we investigate the displacement of water molecules by an apolar probe in the binding pocket of two proteins, cyclin-dependent kinase 2 and tRNA-guanine transglycosylase, using the method of enveloping distribution sampling (EDS) to obtain free enthalpy differences. Water 50-55 cyclin dependent kinase 2 Homo sapiens 124-149 23140174-0 2012 CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90. Serine 65-71 cyclin dependent kinase 2 Homo sapiens 0-4 23140174-4 2012 We also found that inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity, suggesting a functional link between CDK2 and CDK9. Iron 41-45 cyclin dependent kinase 2 Homo sapiens 33-37 23140174-4 2012 We also found that inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity, suggesting a functional link between CDK2 and CDK9. Iron 41-45 cyclin dependent kinase 2 Homo sapiens 135-139 23140174-14 2012 CONCLUSION: Our data indicate that CDK2 phosphorylates CDK9 on Ser 90 and thereby contributes to HIV-1 transcription. Serine 63-66 cyclin dependent kinase 2 Homo sapiens 35-39 22610972-7 2012 Finally, phosphorylation of TAX1BP2 at serine-763 by cyclin-dependent kinase (CDK)2 abolished the TAX1BP2-mediated p38 activation and tumor-suppressive activity, indicating that TAX1BP2 can adapt CDK2 signaling to the p38/p53/p21 pathway. Serine 39-45 cyclin dependent kinase 2 Homo sapiens 78-83 22610972-7 2012 Finally, phosphorylation of TAX1BP2 at serine-763 by cyclin-dependent kinase (CDK)2 abolished the TAX1BP2-mediated p38 activation and tumor-suppressive activity, indicating that TAX1BP2 can adapt CDK2 signaling to the p38/p53/p21 pathway. Serine 39-45 cyclin dependent kinase 2 Homo sapiens 196-200 23096116-4 2012 Here, we show that the ATP non-competitive CDK2/cyclin A inhibitor NBI1 sensitizes erlotinib-resistant tumor cells to the combination treatment (co-treatment) for apoptosis-mediated cell death. Erlotinib Hydrochloride 83-92 cyclin dependent kinase 2 Homo sapiens 43-47 23205069-2 2012 CCRK activates Cdk2, which controls the cell-cycle progression by phosphorylating a threonine residue conserved in Cdk2. Threonine 84-93 cyclin dependent kinase 2 Homo sapiens 15-19 22996593-11 2012 Energetic analysis reveals that van der Waals interaction and non-polar contributions to solvent are favorable in the formation of complexes and amine group of the ligand, which plays a crucial role for binding selectivity between CDK2 and CDK1. Amines 145-150 cyclin dependent kinase 2 Homo sapiens 231-235 22821149-2 2012 BAY 1000394 inhibits the activity of cell-cycle CDKs CDK1, CDK2, CDK3, CDK4, and of transcriptional CDKs CDK7 and CDK9 with IC(50) values in the range between 5 and 25 nmol/L. roniciclib 0-11 cyclin dependent kinase 2 Homo sapiens 59-63 22829544-10 2012 These results indicate that roscovitine stimulated the expression of UGT1A1 by inhibiting CDK2, which phosphorylated PXR at Ser350 to suppress binding with RXR and coactivator and maintain the acetylation of PXR protein. Roscovitine 28-39 cyclin dependent kinase 2 Homo sapiens 90-94 22908236-2 2012 Recently, the same Cdc6 protein was found to exert two more functions in mammalian cells to promote cell proliferation and survival: ATP-dependent activation of p21(CIP1)- or p27(KIP1)-bound Cdk2-cyclin A/E complexes and obstruction of apoptosome assembly and consequent cell death by forming stable complexes with activated Apaf-1 molecules. Adenosine Triphosphate 133-136 cyclin dependent kinase 2 Homo sapiens 191-195 22718513-4 2012 DNA flow cytometric analysis indicated that Zeb induced an S phase arrest of the cell cycle, which was accompanied by the increased levels of cdk2 and cyclin A proteins. pyrimidin-2-one beta-ribofuranoside 44-47 cyclin dependent kinase 2 Homo sapiens 142-146 23205069-2 2012 CCRK activates Cdk2, which controls the cell-cycle progression by phosphorylating a threonine residue conserved in Cdk2. Threonine 84-93 cyclin dependent kinase 2 Homo sapiens 115-119 24280698-4 2012 While butyrate and TSA inhibit VSMC proliferation via cytostatic and cytotoxic effects, respectively, they downregulate cdk4, cdk6, and cdk2, and upregulate cyclin D3, p21Cip1 and p15INK4B, and cause similar effects on key histone H3 posttranslational modifications. Butyrates 6-14 cyclin dependent kinase 2 Homo sapiens 136-140 22893598-2 2012 The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. 8-anilino-1-naphthalenesulfonic acid 86-119 cyclin dependent kinase 2 Homo sapiens 50-54 22893598-2 2012 The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. 8-anilino-1-naphthalenesulfonic acid 121-124 cyclin dependent kinase 2 Homo sapiens 50-54 22893598-2 2012 The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. Adenosine Triphosphate 184-187 cyclin dependent kinase 2 Homo sapiens 50-54 22893598-3 2012 Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. 8-anilino-1-naphthalenesulfonic acid 28-31 cyclin dependent kinase 2 Homo sapiens 60-64 22893598-3 2012 Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. Adenosine Triphosphate 91-94 cyclin dependent kinase 2 Homo sapiens 60-64 22893598-3 2012 Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. Staurosporine 149-162 cyclin dependent kinase 2 Homo sapiens 60-64 22893598-3 2012 Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. Adenosine Triphosphate 181-184 cyclin dependent kinase 2 Homo sapiens 60-64 22893598-3 2012 Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. 8-anilino-1-naphthalenesulfonic acid 209-212 cyclin dependent kinase 2 Homo sapiens 60-64 22893598-6 2012 Although this small compound library contained only ATP-site-directed ligands, the application of this assay to large compound libraries has the potential to reveal previously unrecognized chemical scaffolds suitable for structure-based design of CDK2 inhibitors with new mechanisms of action. Adenosine Triphosphate 52-55 cyclin dependent kinase 2 Homo sapiens 247-251 22891849-3 2012 Kinetic analysis establishes that Cyclin-dependent kinase 2 (CDK2) requires simultaneous binding of two Mg(2+) ions for catalysis of phosphoryl transfer. magnesium ion 104-110 cyclin dependent kinase 2 Homo sapiens 34-59 22891849-3 2012 Kinetic analysis establishes that Cyclin-dependent kinase 2 (CDK2) requires simultaneous binding of two Mg(2+) ions for catalysis of phosphoryl transfer. magnesium ion 104-110 cyclin dependent kinase 2 Homo sapiens 61-65 22891849-7 2012 We present two new crystal structures of CDK2 bound to ADP showing how the phosphate groups can be coordinated by either one or two Mg(2+) ions, with the occupancy of one site in a weaker equilibrium. Adenosine Diphosphate 55-58 cyclin dependent kinase 2 Homo sapiens 41-45 22891849-7 2012 We present two new crystal structures of CDK2 bound to ADP showing how the phosphate groups can be coordinated by either one or two Mg(2+) ions, with the occupancy of one site in a weaker equilibrium. Phosphates 75-84 cyclin dependent kinase 2 Homo sapiens 41-45 22891849-7 2012 We present two new crystal structures of CDK2 bound to ADP showing how the phosphate groups can be coordinated by either one or two Mg(2+) ions, with the occupancy of one site in a weaker equilibrium. magnesium ion 132-138 cyclin dependent kinase 2 Homo sapiens 41-45 24280698-4 2012 While butyrate and TSA inhibit VSMC proliferation via cytostatic and cytotoxic effects, respectively, they downregulate cdk4, cdk6, and cdk2, and upregulate cyclin D3, p21Cip1 and p15INK4B, and cause similar effects on key histone H3 posttranslational modifications. trichostatin A 19-22 cyclin dependent kinase 2 Homo sapiens 136-140 22819191-1 2012 A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline 12-59 cyclin dependent kinase 2 Homo sapiens 195-220 22819841-0 2012 CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species. Reactive Oxygen Species 99-122 cyclin dependent kinase 2 Homo sapiens 0-4 22819841-2 2012 Sublethal doses of H(2)O(2) decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. Hydrogen Peroxide 19-27 cyclin dependent kinase 2 Homo sapiens 189-214 22819841-2 2012 Sublethal doses of H(2)O(2) decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. Hydrogen Peroxide 19-27 cyclin dependent kinase 2 Homo sapiens 216-220 22819841-3 2012 In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H(2)O(2) increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. Water 71-76 cyclin dependent kinase 2 Homo sapiens 90-94 22819841-4 2012 A CDK2 inhibitor, CVT-313, prevented H(2)O(2)-induced cancer cell proliferation. Hydrogen Peroxide 37-45 cyclin dependent kinase 2 Homo sapiens 2-6 22819191-1 2012 A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline 12-59 cyclin dependent kinase 2 Homo sapiens 222-226 22641227-10 2012 Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-beta and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib 0-9 cyclin dependent kinase 2 Homo sapiens 130-135 22641227-10 2012 Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-beta and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. AZD 6244 10-17 cyclin dependent kinase 2 Homo sapiens 130-135 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Threonine 104-107 cyclin dependent kinase 2 Homo sapiens 129-133 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 167-170 cyclin dependent kinase 2 Homo sapiens 20-45 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 167-170 cyclin dependent kinase 2 Homo sapiens 47-51 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 167-170 cyclin dependent kinase 2 Homo sapiens 129-133 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 197-200 cyclin dependent kinase 2 Homo sapiens 20-45 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 197-200 cyclin dependent kinase 2 Homo sapiens 47-51 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Resveratrol 197-200 cyclin dependent kinase 2 Homo sapiens 129-133 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Melphalan 206-209 cyclin dependent kinase 2 Homo sapiens 20-45 22415970-11 2012 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by the combination of RSV with MEL. Melphalan 206-209 cyclin dependent kinase 2 Homo sapiens 129-133 22415970-12 2012 The activity of CDK7, kinase that phosphorylates CDK2 at Thr(160), was inhibited by RSV and by the combination of RSV with MEL. Threonine 57-60 cyclin dependent kinase 2 Homo sapiens 49-53 22415970-12 2012 The activity of CDK7, kinase that phosphorylates CDK2 at Thr(160), was inhibited by RSV and by the combination of RSV with MEL. Resveratrol 84-87 cyclin dependent kinase 2 Homo sapiens 49-53 22415970-12 2012 The activity of CDK7, kinase that phosphorylates CDK2 at Thr(160), was inhibited by RSV and by the combination of RSV with MEL. Resveratrol 114-117 cyclin dependent kinase 2 Homo sapiens 49-53 22415970-12 2012 The activity of CDK7, kinase that phosphorylates CDK2 at Thr(160), was inhibited by RSV and by the combination of RSV with MEL. Melphalan 123-126 cyclin dependent kinase 2 Homo sapiens 49-53 22422660-7 2012 Combined administration of furanodiene and TAM led to marked increase in growth inhibition, cell cycle arrest and pro-apoptotic activity in ERa-positive cells compared to individual agent, and enhanced the down-regulation of p-cyclin D1, cyclin D1, CDK2, CDK6, p-Rb, Rb and p-p44, and the up-regulation of p27, Bax and Bad, but did not show increased cytotoxicity in ERa-negative MCF-10A non-tumorigenic breast epithelial cells. furanodiene 27-38 cyclin dependent kinase 2 Homo sapiens 249-253 22422660-7 2012 Combined administration of furanodiene and TAM led to marked increase in growth inhibition, cell cycle arrest and pro-apoptotic activity in ERa-positive cells compared to individual agent, and enhanced the down-regulation of p-cyclin D1, cyclin D1, CDK2, CDK6, p-Rb, Rb and p-p44, and the up-regulation of p27, Bax and Bad, but did not show increased cytotoxicity in ERa-negative MCF-10A non-tumorigenic breast epithelial cells. Tamoxifen 43-46 cyclin dependent kinase 2 Homo sapiens 249-253 21424700-0 2012 Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. Mifepristone 44-52 cyclin dependent kinase 2 Homo sapiens 125-150 22465179-10 2012 Honokiol induced G1 cell cycle arrest by reducing the expression of cyclins D1, D2, E, CDK2, CDK4, CDK6 and c-Myc, while apoptosis was induced via reduced expression of cIAP-2, XIAP and survivin. honokiol 0-8 cyclin dependent kinase 2 Homo sapiens 87-91 22462738-11 2012 Furthermore, capsaicin inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with the inhibition of CDK2, CDK4 and CDK6. Capsaicin 13-22 cyclin dependent kinase 2 Homo sapiens 121-125 22552501-3 2012 7,8-DHF-induced G1 arrest was correlated with downregulation of cyclin E, with a concomitant upregulation of cyclin-dependent kinase (Cdk) inhibitors including p27, and association of p27 with Cdk2 was markedly induced in 7,8-DHF-treated cells. 6,7-dihydroxyflavone 0-7 cyclin dependent kinase 2 Homo sapiens 229-233 22584582-0 2012 Successive phosphorylation of p27(KIP1) protein at serine-10 and C terminus crucially controls its potency to inactivate Cdk2. Serine 51-57 cyclin dependent kinase 2 Homo sapiens 121-125 22584582-1 2012 During the G(1)-S transition, the activity of Cdk2 is regulated by its association with p27(KIP1), which in rodent fibroblasts undergoes phosphorylation mainly at serine 10, threonine 187, and C-terminal threonine 197 by KIS, Cdk2, and Pim or ROCK, respectively. Serine 163-169 cyclin dependent kinase 2 Homo sapiens 46-50 22584582-1 2012 During the G(1)-S transition, the activity of Cdk2 is regulated by its association with p27(KIP1), which in rodent fibroblasts undergoes phosphorylation mainly at serine 10, threonine 187, and C-terminal threonine 197 by KIS, Cdk2, and Pim or ROCK, respectively. Threonine 174-183 cyclin dependent kinase 2 Homo sapiens 46-50 22584582-1 2012 During the G(1)-S transition, the activity of Cdk2 is regulated by its association with p27(KIP1), which in rodent fibroblasts undergoes phosphorylation mainly at serine 10, threonine 187, and C-terminal threonine 197 by KIS, Cdk2, and Pim or ROCK, respectively. Threonine 204-213 cyclin dependent kinase 2 Homo sapiens 46-50 22584582-4 2012 We report here that serine 10 phosphorylation is required for efficient C-terminal phosphorylation of its own by PIM and ROCK kinases and critically controls the potency of p27 as a Cdk2 inhibitor. Serine 20-26 cyclin dependent kinase 2 Homo sapiens 182-186 22417066-6 2012 The antiproliferative effect of XRT/RSV treatment correlated with increased expression of p15, p21, and mutant p53 and decreased expression of cyclin B, cyclin D, and cdk2. Resveratrol 36-39 cyclin dependent kinase 2 Homo sapiens 167-171 22610825-7 2012 Western blotting and real-time quantitative PCR showed that DHA and EPA decreased cyclin E and CDK2 levels at both the protein and mRNA level. Dihydroalprenolol 60-63 cyclin dependent kinase 2 Homo sapiens 95-99 22610825-7 2012 Western blotting and real-time quantitative PCR showed that DHA and EPA decreased cyclin E and CDK2 levels at both the protein and mRNA level. Eicosapentaenoic Acid 68-71 cyclin dependent kinase 2 Homo sapiens 95-99 22641337-0 2012 Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway. Water 0-5 cyclin dependent kinase 2 Homo sapiens 195-199 22641337-0 2012 Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway. Fluorouracil 150-164 cyclin dependent kinase 2 Homo sapiens 195-199 22641337-9 2012 In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FU in the absence of overt toxicity by downregulating the mRNA and protein levels of CDK2, cyclin E and E2F1. Fluorouracil 74-78 cyclin dependent kinase 2 Homo sapiens 185-189 22927831-5 2012 That plasticity obscured a requirement for Cdk2 activity in proliferation of human cells, which we uncovered by replacement of wild-type Cdk2 with a mutant version sensitized to inhibition by bulky adenine analogs. Adenine 198-205 cyclin dependent kinase 2 Homo sapiens 43-47 22927831-5 2012 That plasticity obscured a requirement for Cdk2 activity in proliferation of human cells, which we uncovered by replacement of wild-type Cdk2 with a mutant version sensitized to inhibition by bulky adenine analogs. Adenine 198-205 cyclin dependent kinase 2 Homo sapiens 137-141 22927831-7 2012 In extracts supplemented with an ATP analog used preferentially by AS kinases, Cdk2(as) phosphorylated the Nijmegen Breakage Syndrome gene product Nbs1-a component of the conserved Mre11-Rad50-Nbs1 complex required for normal DNA damage repair and checkpoint signaling-dependent on a consensus CDK recognition site at Ser432. Adenosine Triphosphate 33-36 cyclin dependent kinase 2 Homo sapiens 79-83 22927831-7 2012 In extracts supplemented with an ATP analog used preferentially by AS kinases, Cdk2(as) phosphorylated the Nijmegen Breakage Syndrome gene product Nbs1-a component of the conserved Mre11-Rad50-Nbs1 complex required for normal DNA damage repair and checkpoint signaling-dependent on a consensus CDK recognition site at Ser432. Adenosine Triphosphate 33-36 cyclin dependent kinase 2 Homo sapiens 294-297 22716215-11 2012 The combination of 5-FU and chloroquine induced G1 arrest, up-regulation of p27 and p53, and down-regulation of CDK2 and cyclin D1. Fluorouracil 19-23 cyclin dependent kinase 2 Homo sapiens 112-116 22716215-11 2012 The combination of 5-FU and chloroquine induced G1 arrest, up-regulation of p27 and p53, and down-regulation of CDK2 and cyclin D1. Chloroquine 28-39 cyclin dependent kinase 2 Homo sapiens 112-116 22564725-8 2012 Proliferation of tamoxifen-resistant cells was inhibited by RNAi-mediated knockdown of cyclin E1, cyclin E2, or CDK2. Tamoxifen 17-26 cyclin dependent kinase 2 Homo sapiens 112-116 22564725-9 2012 Furthermore, CDK2 inhibition of E-cyclin overexpressing cells and tamoxifen-resistant cells restored sensitivity to tamoxifen or CDK4 inhibition. Tamoxifen 116-125 cyclin dependent kinase 2 Homo sapiens 13-17 22665354-7 2012 Furthermore, capsaicin suppressed the cell cycle progression at the G1/S phase in FaDu cells by decreasing the expression of the regulators of cyclin B1 and D1, as well as cyclin-dependent protein kinases cdk-1, cdk-2 and cdk-4. Capsaicin 13-22 cyclin dependent kinase 2 Homo sapiens 212-217 22114764-6 2012 In butein-treated cells, there was a marked decrease in the protein expression of cyclins D1, D2, and E and cdks 2, 4, and 6 with concomitant induction of WAF1/p21 and KIP1/p27. butein 3-9 cyclin dependent kinase 2 Homo sapiens 82-117 21424700-0 2012 Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. cdb 69-72 cyclin dependent kinase 2 Homo sapiens 125-150 22661920-6 2012 The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. calcein AM 145-155 cyclin dependent kinase 2 Homo sapiens 92-96 22234939-7 2012 Flow cytometric analysis indicated that L-165041 reduced the number of ECs in the S phase and the expression levels of cell cycle regulatory proteins such as cyclin A, cyclin E, CDK2, and CDK4; phosphorylation of the retinoblastoma protein was suppressed by pretreatment with L-165041. l 40-41 cyclin dependent kinase 2 Homo sapiens 178-182 22234939-7 2012 Flow cytometric analysis indicated that L-165041 reduced the number of ECs in the S phase and the expression levels of cell cycle regulatory proteins such as cyclin A, cyclin E, CDK2, and CDK4; phosphorylation of the retinoblastoma protein was suppressed by pretreatment with L-165041. 4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid 40-48 cyclin dependent kinase 2 Homo sapiens 178-182 22802695-4 2012 Western blotting on the expression of cell cycle inhibitors showed that p21 and p27 was up-regulated as ethanol concentration increases from 0 to 1.5% whilst the cell cycle regulators, cdk1, cdk2, and cdk4 as well as Cyclin A, Cyclin B1 and Cyclin E1, were gradually down-regulated. Ethanol 104-111 cyclin dependent kinase 2 Homo sapiens 191-195 22661920-6 2012 The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Pentosephosphates 303-320 cyclin dependent kinase 2 Homo sapiens 92-96 22542944-5 2012 The SKLB70326-mediated cell-cycle arrest was associated with the downregulation of cyclin-dependent kinase (CDK) 2, CDK4 and CDK6 but not cyclin D1 or cyclin E. The phosphorylation of the retinoblastoma protein (Rb) was also observed. 3-amino-6-(3-methoxyphenyl)thieno(2.3-b)pyridine-2-carboxamide 4-13 cyclin dependent kinase 2 Homo sapiens 83-114 21563217-7 2012 The TB-induced cell-cycle arrest occurred when the cyclin-dependent kinase 2 activity was inhibited just as the protein levels of p21(cip1) and p27(kip1) were increased. Terbinafine 4-6 cyclin dependent kinase 2 Homo sapiens 51-76 22383427-4 2012 (3)H-thymidine incorporation assays revealed that sorafenib causes a dose-dependent inhibition of proliferation of all cell lines associated with downregulation of cyclin-dependent kinase 2 and cyclin D1 expression. Sorafenib 50-59 cyclin dependent kinase 2 Homo sapiens 164-189 22366652-14 2012 The selective inhibition of cancer cell growth, the apoptosis induction via the mitochondrial pathway, and the G0/G1 arrest by modulating the PI3K/AKT signaling pathway and downregulating cyclin D1, which leads to the release of p27kip1 and the association of this inhibitor with the cyclin E/CDK2 complex, ultimately preventing cell-cycle progression from G1 to S phase, all serve to provide support for further studies of tehranolide as a possible anticancer drug in the clinical treatment of cancer. tehranolide 424-435 cyclin dependent kinase 2 Homo sapiens 293-297 21997969-4 2012 Tanshinone IIA induced cell cycle arrest at G1 phase and down-regulated cyclin D1, CDK2 and CDK4. tanshinone 0-10 cyclin dependent kinase 2 Homo sapiens 83-87 22285700-0 2012 Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells. bufalin 0-7 cyclin dependent kinase 2 Homo sapiens 88-92 22185819-4 2012 Concurrent with the cell cycle arrest of MCF7 cells, artemisinin selectively downregulated the transcript and protein levels of the CDK2 and CDK4 cyclin-dependent kinases, cyclin E, cyclin D1, and the E2F1 transcription factor. artemisinin 53-64 cyclin dependent kinase 2 Homo sapiens 132-136 22185819-5 2012 Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 gene expression was accounted for by the loss of CDK2 promoter activity. artemisinin 73-84 cyclin dependent kinase 2 Homo sapiens 12-16 22185819-5 2012 Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 gene expression was accounted for by the loss of CDK2 promoter activity. artemisinin 73-84 cyclin dependent kinase 2 Homo sapiens 97-101 22185819-5 2012 Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 gene expression was accounted for by the loss of CDK2 promoter activity. artemisinin 73-84 cyclin dependent kinase 2 Homo sapiens 97-101 22185819-6 2012 Chromatin immunoprecipitation revealed that artemisinin inhibited E2F1 interactions with the endogenous MCF7 cell CDK2 and cyclin E promoters. artemisinin 44-55 cyclin dependent kinase 2 Homo sapiens 114-118 20946258-4 2012 Our previous study has demonstrated that simvastatin inhibits VSMC proliferation in high glucose status without dyslipidemia, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and upregulation of p53, p21, p16, and p27. Simvastatin 41-52 cyclin dependent kinase 2 Homo sapiens 243-247 21821547-0 2012 Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers. Paclitaxel 103-113 cyclin dependent kinase 2 Homo sapiens 65-69 21821547-0 2012 Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers. Fluorouracil 126-140 cyclin dependent kinase 2 Homo sapiens 65-69 21821547-0 2012 Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers. Epirubicin 142-152 cyclin dependent kinase 2 Homo sapiens 65-69 21821547-0 2012 Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers. Cyclophosphamide 157-173 cyclin dependent kinase 2 Homo sapiens 65-69 21695458-5 2012 We hypothesized that because LMW-E binds to CDK2 more efficiently than full length cyclin E, resulting in increased activity, CDK inhibitors could be used to target tumors with LMW-E bound to CDK2. lmw-e 29-34 cyclin dependent kinase 2 Homo sapiens 44-48 21695458-5 2012 We hypothesized that because LMW-E binds to CDK2 more efficiently than full length cyclin E, resulting in increased activity, CDK inhibitors could be used to target tumors with LMW-E bound to CDK2. lmw-e 29-34 cyclin dependent kinase 2 Homo sapiens 192-196 22527961-3 2012 Macrocycles with a basic nitrogen in the linker form a salt bridge with Asp86 in CDK2 and Asp698 in FLT3. Nitrogen 25-33 cyclin dependent kinase 2 Homo sapiens 81-85 22160829-7 2012 Based on this result, the change of proteins related in checkpoint pathway was examined over a time course of 0.5-24 h. Treatment of HT29 cells with widdrol elicits the following: (1) phosphorylation of Chk2 and p53, (2) reduction of cell division cycle 25A (Cdc25A) expression, (3) increase of Cdk inhibitor p21 expression, and (4) decrease of the levels of Cdk2 and cyclin E expression in a time-dependent manner. widdrol 149-156 cyclin dependent kinase 2 Homo sapiens 359-363 22369944-5 2012 Both ex vivo and in vitro experiments showed that phosphorylation by MAPK/Cyclin A/cdk2 and GSK3beta protected C/EBPbeta from mu-calpain-mediated proteolysis, while phosphorylation on Thr(188) by MAPK/Cyclin A/cdk2 contributed more to the stabilization of C/EBPbeta, Further studies indicated that phosphorylation mimic C/EBPbeta was insensitive to both calpain accelerator and calpain inhibitor. Threonine 184-187 cyclin dependent kinase 2 Homo sapiens 83-87 21697511-4 2012 Specifically, binding of Cks1 or Cks2 to cyclin-dependent kinase 2 confers partial resistance to the effects of inhibitory tyrosine phosphorylation mediated by the intra-S-phase checkpoint, allowing cells to continue replicating DNA even under conditions of replicative stress. Tyrosine 123-131 cyclin dependent kinase 2 Homo sapiens 41-66 22399317-11 2012 Tyrosine phosphorylation relieves kinase inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue within the flexible C-terminus of p27. Tyrosine 0-8 cyclin dependent kinase 2 Homo sapiens 64-68 22253097-0 2012 Monocillin II inhibits human breast cancer growth partially by inhibiting MAPK pathways and CDK2 Thr160 phosphorylation. monocillin II 0-13 cyclin dependent kinase 2 Homo sapiens 92-96 22253097-3 2012 We demonstrated for the first time that monocillin II could arrest breast cancer cell cycle in G1 phase, which might partially be the result of its inhibition effect on the phosphorylation of the Thr160 residue of cyclin dependent kinase 2 (CDK2), a key enzyme in cell-cycle regulation. monocillin II 40-53 cyclin dependent kinase 2 Homo sapiens 214-239 22253097-3 2012 We demonstrated for the first time that monocillin II could arrest breast cancer cell cycle in G1 phase, which might partially be the result of its inhibition effect on the phosphorylation of the Thr160 residue of cyclin dependent kinase 2 (CDK2), a key enzyme in cell-cycle regulation. monocillin II 40-53 cyclin dependent kinase 2 Homo sapiens 241-245 22253097-5 2012 Remarkably, we found that monocillin II could inhibit activation of MAPKs including ERK, JNK and p38, which might be involved in the inactivation of CDK2. monocillin II 26-39 cyclin dependent kinase 2 Homo sapiens 149-153 22072628-4 2012 TauF4 was phosphorylated by the proline-directed CDK2/CycA3 kinase on Thr231 (generating the AT180 epitope), Ser235, and equally on Thr212 and Thr217 in the Proline-rich region (Tau[Ser208-Gln244] or PRR). tauf4 0-5 cyclin dependent kinase 2 Homo sapiens 49-53 22072628-4 2012 TauF4 was phosphorylated by the proline-directed CDK2/CycA3 kinase on Thr231 (generating the AT180 epitope), Ser235, and equally on Thr212 and Thr217 in the Proline-rich region (Tau[Ser208-Gln244] or PRR). Proline 32-39 cyclin dependent kinase 2 Homo sapiens 49-53 22399317-11 2012 Tyrosine phosphorylation relieves kinase inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue within the flexible C-terminus of p27. Threonine 99-108 cyclin dependent kinase 2 Homo sapiens 64-68 22021906-6 2012 PKC-iota directly associated and phosphorylated Cdk7 at T170 in a cell cycle-dependent manner, phosphorylating its downstream target, cdk2 at T160. iota 4-8 cyclin dependent kinase 2 Homo sapiens 134-138 22021906-9 2012 PKC-iota downregulation reduced Cdk7 and cdk2 phosphorylation following PI (3)-kinase inhibition, phosphotidylinositol-dependent kinase 1 knockdown as well as PKC-iota silencing (by siRNA treatment). iota 4-8 cyclin dependent kinase 2 Homo sapiens 41-45 22021906-12 2012 These findings suggest that glioma cells may be proliferating through a novel PI (3)-kinase-/PKC-iota/Cdk7/cdk2-mediated pathway. iota 97-101 cyclin dependent kinase 2 Homo sapiens 107-111 22919418-7 2012 PEITC induced G(0)/G(1) phase arrest through the effects of associated protein such as p53, p21, p17, CDK2 and cyclin E, and it triggered apoptosis through promotion of Bax and Bid expression and reduction of Bcl-2, leading to decrease the levels of mitochondrial membrane potential (DeltaPsi(m)), and followed the releases of cytochrome c, AIF and Endo G then for causing apoptosis in HSC-3 cells. phenethyl isothiocyanate 0-5 cyclin dependent kinase 2 Homo sapiens 102-106 22415097-6 2012 The SKLB70359 induced G0/G1 cell cycle arrest was characterized by down-regulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6 expression and up-regulation of p53, p21(WAF1). 3-amino-6-(3,4-dichlorophenyl)thieno(2,3-b)pyridine-2-carboxamide 4-13 cyclin dependent kinase 2 Homo sapiens 86-111 22415097-6 2012 The SKLB70359 induced G0/G1 cell cycle arrest was characterized by down-regulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6 expression and up-regulation of p53, p21(WAF1). 3-amino-6-(3,4-dichlorophenyl)thieno(2,3-b)pyridine-2-carboxamide 4-13 cyclin dependent kinase 2 Homo sapiens 113-117 22854281-10 2012 The protein expressions of p-cyclin D1, total cyclin D1, p-CDK2, total CDK2, p-Rb, total Rb, Bcl-xL, and Akt were significantly inhibited by furanodiene, whereas the protein expressions of Bad and Bax, and the proteolytic cleavage of caspase-9, caspase-7, and poly-ADP-ribose polymerase (PARP) were dramatically increased. furanodiene 141-152 cyclin dependent kinase 2 Homo sapiens 59-63 22854281-10 2012 The protein expressions of p-cyclin D1, total cyclin D1, p-CDK2, total CDK2, p-Rb, total Rb, Bcl-xL, and Akt were significantly inhibited by furanodiene, whereas the protein expressions of Bad and Bax, and the proteolytic cleavage of caspase-9, caspase-7, and poly-ADP-ribose polymerase (PARP) were dramatically increased. furanodiene 141-152 cyclin dependent kinase 2 Homo sapiens 71-75 22466726-0 2012 Synthesis and structure of the beta-carboline derivatives and their binding intensity with cyclin-dependent kinase 2. norharman 31-45 cyclin dependent kinase 2 Homo sapiens 91-116 22466726-2 2012 In addition, the binding mode of these beta-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. norharman 39-53 cyclin dependent kinase 2 Homo sapiens 71-96 22466726-2 2012 In addition, the binding mode of these beta-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. norharman 39-53 cyclin dependent kinase 2 Homo sapiens 98-102 22150677-10 2012 CONCLUSIONS: Downregulation of the mRNA levels of CDK2, CDK4 and cyclin D1 and upregulation of p21 might be a possible mechanism for the inhibition of proliferation induced by alteronol in HeLa cells. alteronol 176-185 cyclin dependent kinase 2 Homo sapiens 50-54 22368399-3 2012 AIM: This in silico study aimed to predict the main mechanism of fucoxanthin; whether with its binding to p53 gene, CDK2, or tubulin. fucoxanthin 65-76 cyclin dependent kinase 2 Homo sapiens 116-120 22583615-6 2012 The DNA damage cascades triggered by GL331 finally induced the inactivation of cyclin A/Cdk2 complexes to some extent. GL 331 37-42 cyclin dependent kinase 2 Homo sapiens 88-92 21918011-8 2012 Finally, Rta-induced p21 expression diminished the activity of CDK2/cyclin E complex, and, Rta-induced 14-3-3sigma expression sequestered CDK1 and CDK2 in the cytoplasm. 3-3sigma 106-114 cyclin dependent kinase 2 Homo sapiens 147-151 22850597-3 2012 Our western blot analysis showed that berberine-induced G1 cell cycle arrest was mediated through the increased expression of cyclin-dependent kinase inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. Berberine 38-47 cyclin dependent kinase 2 Homo sapiens 229-233 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 223-226 cyclin dependent kinase 2 Homo sapiens 60-64 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 90-93 cyclin dependent kinase 2 Homo sapiens 33-58 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 90-93 cyclin dependent kinase 2 Homo sapiens 60-64 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 90-93 cyclin dependent kinase 2 Homo sapiens 133-137 22686307-5 2012 Among the G(1) phase cell cycle-related proteins, levels of the retinoblastoma protein (RB), which is known to interact with AhR, and levels of the cyclin dependent kinase (CDK) 6 were reduced by eugenol and isoeugenol, whereas steady-state levels of CDK2 and CDK4 remained unaffected. Eugenol 196-203 cyclin dependent kinase 2 Homo sapiens 251-255 22686307-5 2012 Among the G(1) phase cell cycle-related proteins, levels of the retinoblastoma protein (RB), which is known to interact with AhR, and levels of the cyclin dependent kinase (CDK) 6 were reduced by eugenol and isoeugenol, whereas steady-state levels of CDK2 and CDK4 remained unaffected. isoeugenol 208-218 cyclin dependent kinase 2 Homo sapiens 251-255 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 223-226 cyclin dependent kinase 2 Homo sapiens 33-58 22072796-3 2012 Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Serine 223-226 cyclin dependent kinase 2 Homo sapiens 133-137 22479189-11 2012 LMW-E requires CDK2-associated kinase activity to induce mammary tumor formation by disrupting acinar development. lmw-e 0-5 cyclin dependent kinase 2 Homo sapiens 15-19 21947091-12 2012 In conclusion, SB induces G1 and G2 arrest by increasing p21 expression resulting in CDK2, CDK4 and CDK6 down-regulation. Butyric Acid 27-29 cyclin dependent kinase 2 Homo sapiens 97-101 22768064-3 2012 However, the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression. Rubidium 30-32 cyclin dependent kinase 2 Homo sapiens 126-130 23028682-0 2012 Phosphorylation of Rad9 at serine 328 by cyclin A-Cdk2 triggers apoptosis via interfering Bcl-xL. Serine 27-33 cyclin dependent kinase 2 Homo sapiens 50-54 23028682-4 2012 Cyclin A-Cdk2 catalyzed the phosphorylation of Rad9 at serine 328 in HeLa cells during apoptosis induced by etoposide, an inhibitor of topoisomeraseII. Serine 55-61 cyclin dependent kinase 2 Homo sapiens 9-13 23028682-4 2012 Cyclin A-Cdk2 catalyzed the phosphorylation of Rad9 at serine 328 in HeLa cells during apoptosis induced by etoposide, an inhibitor of topoisomeraseII. Etoposide 108-117 cyclin dependent kinase 2 Homo sapiens 9-13 23028682-6 2012 The forced activation of cyclin A-Cdk2 in these cells by the overexpression of cyclin A,triggered Rad9 phosphorylation at serine 328 and thereby promoted the interaction of Rad9 with Bcl-xL and the subsequent initiation of the apoptotic program. Serine 122-128 cyclin dependent kinase 2 Homo sapiens 34-38 22952775-5 2012 Treatment of pancreatic cancer cells with pristimerin also resulted in G1-phase arrest which was strongly associated with a marked decrease in the level of cyclins (D1 and E) and cyclin-dependent kinases (cdk2, cdk4 and cdk6 ) with concomitant induction of WAF1/p21 and KIP1/p27. pristimerin 42-53 cyclin dependent kinase 2 Homo sapiens 205-209 23071779-5 2012 Evidence indicates that Skp2 targets beta-TrCP for degradation via the cyclin-dependent kinase 2-facilitated recognition of the proline-directed phosphorylation motif (412)SP. Proline 128-135 cyclin dependent kinase 2 Homo sapiens 71-96 22479587-7 2012 NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expression of Cdk2 and CDC20 proteins. naha 0-4 cyclin dependent kinase 2 Homo sapiens 121-125 22558186-7 2012 CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Serine 103-109 cyclin dependent kinase 2 Homo sapiens 0-4 22558186-7 2012 CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Threonine 117-126 cyclin dependent kinase 2 Homo sapiens 0-4 21153447-12 2011 If the gene expression data for cyclin D1, cyclin G2, cdk2, cdk6 and cdk inhibtor 2B were used, the overall FDG uptake as measured by the SUV could be predicted with r = 0.75. Fluorodeoxyglucose F18 108-111 cyclin dependent kinase 2 Homo sapiens 54-58 22359572-6 2012 DHC caused G0/G1 cell cycle arrest, which was associated with the down-regulation of cyclin D1 expression, leading to the suppression of retinoblastoma protein phosphorylation and subsequent inhibition of cyclin A and cdk2 expression. dehydrocostus lactone 0-3 cyclin dependent kinase 2 Homo sapiens 218-222 21907187-4 2011 Western blot analysis revealed that lovastatin caused an increase of the protein level of p27 and cyclin-dependent kinase (CDK)4 and a decrease of the protein level of cyclin A2, cyclin D3, and phosphorylated Rb (pRb), but did not significantly change the protein levels of p21, cyclins D1 and E, and CDK2, in ARO cells. Lovastatin 36-46 cyclin dependent kinase 2 Homo sapiens 301-305 21907187-5 2011 The formation of the CDK2-p27 complex was increased and the CDK2 activity was decreased in the lovastatin-treated ARO cells. Lovastatin 95-105 cyclin dependent kinase 2 Homo sapiens 21-25 21907187-5 2011 The formation of the CDK2-p27 complex was increased and the CDK2 activity was decreased in the lovastatin-treated ARO cells. Lovastatin 95-105 cyclin dependent kinase 2 Homo sapiens 60-64 22000924-0 2011 Design, synthesis and biological study of novel pyrido[2,3-d]pyrimidine as anti-proliferative CDK2 inhibitors. Pyrido[2,3-d]pyrimidine 48-71 cyclin dependent kinase 2 Homo sapiens 94-98 22000924-4 2011 Molecular modeling study, including fitting to a 3D-pharmacophore model, docking into cyclin dependant kinase2 (CDK2) active site and binding energy calculations were carried out and these studies suggested the same binding orientation inside the CDK2 binding pocket for these analogs compared to ATP. Adenosine Triphosphate 297-300 cyclin dependent kinase 2 Homo sapiens 112-116 22000924-4 2011 Molecular modeling study, including fitting to a 3D-pharmacophore model, docking into cyclin dependant kinase2 (CDK2) active site and binding energy calculations were carried out and these studies suggested the same binding orientation inside the CDK2 binding pocket for these analogs compared to ATP. Adenosine Triphosphate 297-300 cyclin dependent kinase 2 Homo sapiens 247-251 20957523-2 2011 It can specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes, including several oncogenes (e.g., N-myc, CrkL, Wnt10b, RIZ and hTERT) and genes involved in the control of cell cycle (e.g., CyclinG1 and CDK2) and signal transduction (e.g., STAT1, MAP3K11 and PIK3CB). Lysine 44-50 cyclin dependent kinase 2 Homo sapiens 253-257 22036212-0 2011 Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro. 6-(het) ary xylocydine 13-35 cyclin dependent kinase 2 Homo sapiens 101-105 22036212-1 2011 A series of purine nucleoside analogues bearing an aryl and hetaryl group in position 6 were prepared and their biological activities were assessed by in vitro CDK1/Cyclin B1 and CDK2/Cyclin A2 kinase assay. Purine Nucleosides 12-29 cyclin dependent kinase 2 Homo sapiens 179-183 22036212-2 2011 From the synthesized chemicals, three Xylocydine derivatives 3h, 3i, and 3j exhibited specific inhibitory activities on CDK2/Cyclin A2 with IC(50) values of 4.6, 4.8, and 55 muM, respectively. 4-amino-6-bromo-7-(xylofuranosyl)pyrrolo(2,3-d)pyrimidine-5-carboxamide 38-48 cyclin dependent kinase 2 Homo sapiens 120-124 20532678-7 2011 Down-regulation of pSrcY416 led to up-regulation of p21Cip1 and p27Kip1 in both HeLa and SiHa cells and decreased the expression of cyclin A1, cyclin E, and cyclin-dependent kinase-2,-6 (CDK-2,-6) in HeLa cells and of cyclin B and CDK-2 in SiHa cells. psrcy416 19-27 cyclin dependent kinase 2 Homo sapiens 157-185 20532678-7 2011 Down-regulation of pSrcY416 led to up-regulation of p21Cip1 and p27Kip1 in both HeLa and SiHa cells and decreased the expression of cyclin A1, cyclin E, and cyclin-dependent kinase-2,-6 (CDK-2,-6) in HeLa cells and of cyclin B and CDK-2 in SiHa cells. psrcy416 19-27 cyclin dependent kinase 2 Homo sapiens 187-192 20532678-7 2011 Down-regulation of pSrcY416 led to up-regulation of p21Cip1 and p27Kip1 in both HeLa and SiHa cells and decreased the expression of cyclin A1, cyclin E, and cyclin-dependent kinase-2,-6 (CDK-2,-6) in HeLa cells and of cyclin B and CDK-2 in SiHa cells. psrcy416 19-27 cyclin dependent kinase 2 Homo sapiens 231-236 21965652-5 2011 In this study, we demonstrate that MCM3 is a substrate of cyclin E/Cdk2 and can be phosphorylated by cyclin E/Cdk2 at Thr-722. Threonine 118-121 cyclin dependent kinase 2 Homo sapiens 110-114 21958871-0 2011 Involvement of Chk1-Cdc25A-cyclin A/CDK2 pathway in simvastatin induced S-phase cell cycle arrest and apoptosis in multiple myeloma cells. Simvastatin 52-63 cyclin dependent kinase 2 Homo sapiens 36-40 21958871-5 2011 The results of western blot showed that simvastatin-induced S-phase cell cycle arrest was associated with activation of Chk1, downregulation of Cdc25A, cyclin A and CDK2 expression. Simvastatin 40-51 cyclin dependent kinase 2 Homo sapiens 165-169 21958871-7 2011 Further investigation revealed that silence of Chk1 expression by Chk1 specific siRNA inhibited simvastatin-induced activation of Chk1, downregulation of Cdc25A, cyclin A and CDK2 expression, and diminished S phase cell cycle arrest. Simvastatin 96-107 cyclin dependent kinase 2 Homo sapiens 175-179 21958871-9 2011 These results suggested that the Chk1-Cdc25A-cyclin A/CDk2 pathway was involved in simvastatin-induced S-phase cell cycle arrest and apoptosis in multiple myeloma cell lines. Simvastatin 83-94 cyclin dependent kinase 2 Homo sapiens 54-58 21965652-10 2011 Other studies indicate that excess of MCM3 up-regulates the phosphorylation of CHK1 Ser-345 and CDK2 Thr-14. Threonine 101-104 cyclin dependent kinase 2 Homo sapiens 96-100 22110187-5 2011 Western blot analysis of cell lysate showed that ASO inhibited the de novo synthesis of CD1, CD3, and CDK2 in multiple cell lines. Oligonucleotides, Antisense 49-52 cyclin dependent kinase 2 Homo sapiens 102-106 21982796-2 2011 Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. Purines 40-47 cyclin dependent kinase 2 Homo sapiens 128-132 21908486-7 2011 Honokiol down-regulated the expression of cyclin D1, cyclin D2, Cdk2, Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk"s inhibitor proteins p21 and p27. honokiol 0-8 cyclin dependent kinase 2 Homo sapiens 64-68 22308692-6 2011 Then RT-PCR and Western blot assay were employed to detect the expressions of c-myc, p27, CDK2 and cyclinE1 in HL-60 cells after exposure to TMP. Thymidine Monophosphate 141-144 cyclin dependent kinase 2 Homo sapiens 90-94 21843532-9 2011 This suggests the inhibitory effect of genistein on the induction of extra centrosomes occurs through the inactivation of CDK2/Cyclin-A/E via p21 up-regulation. Genistein 39-48 cyclin dependent kinase 2 Homo sapiens 122-126 21872392-5 2011 Furthermore, fullerenes induced CDK2 expression and activated NF-kappaB and NFAT in splenocytes at 6 days post-administration. Fullerenes 13-23 cyclin dependent kinase 2 Homo sapiens 32-36 21851826-8 2011 Inhibition of calcineurin activity by cyclosporine A or loss of NFATc2 protein by siRNA transfection abolished serotonin-induced cyclin A expression and consequent CDK2 activation and DNA synthesis. Serotonin 111-120 cyclin dependent kinase 2 Homo sapiens 164-168 21851826-9 2011 We further found that pretreatment of cells with sildenafil suppressed serotonin-triggered activation of calcineurin/NFATc2 signaling pathway and resultant cyclin A expression, CDK2 activation and cell proliferation, while the presence of DT-3 [a specific protein kinase G (PKG) peptide inhibitor] reversed the effects of sildenafil on PASMCs. Sildenafil Citrate 49-59 cyclin dependent kinase 2 Homo sapiens 177-181 21851826-9 2011 We further found that pretreatment of cells with sildenafil suppressed serotonin-triggered activation of calcineurin/NFATc2 signaling pathway and resultant cyclin A expression, CDK2 activation and cell proliferation, while the presence of DT-3 [a specific protein kinase G (PKG) peptide inhibitor] reversed the effects of sildenafil on PASMCs. Serotonin 71-80 cyclin dependent kinase 2 Homo sapiens 177-181 21600278-8 2011 Finally, both the growth inhibition and the down-regulation of CDKs induced by esculetin were suppressed by either SB203580 or the DN p38 MAPK mutant gene. esculetin 79-88 cyclin dependent kinase 2 Homo sapiens 63-67 21801719-6 2011 In HCC, cyclins A, E, D1, CDK2 and CDK4 protein overexpression was detected in 52.8%, 52.8%, 69%, 47% and 58% compared to 36.1%, 33%, 56%, 27.8%, 55.6% for CH and 36.1%, 27%, 30.6%, 27%, 50% for PCF. PHENYL CHLOROFORMATE 195-198 cyclin dependent kinase 2 Homo sapiens 26-30 22368708-0 2011 Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes. platinum(ii) phenanthroline 94-121 cyclin dependent kinase 2 Homo sapiens 58-83 22368708-0 2011 Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes. platinum(ii) phenanthroline 94-121 cyclin dependent kinase 2 Homo sapiens 85-89 22368708-2 2011 Herein, in an effort to investigate the potential biological utility of metal-based compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. Metals 72-77 cyclin dependent kinase 2 Homo sapiens 181-206 21600278-8 2011 Finally, both the growth inhibition and the down-regulation of CDKs induced by esculetin were suppressed by either SB203580 or the DN p38 MAPK mutant gene. SB 203580 115-123 cyclin dependent kinase 2 Homo sapiens 63-67 21600278-9 2011 In conclusion, these results demonstrate that activation of p38 MAPK contributes to esculetin-induced p21WAF1 expression in VSMC by decreasing both the cyclin D1/CDK4 and cyclin E/CDK2 complexes. esculetin 84-93 cyclin dependent kinase 2 Homo sapiens 180-184 21824779-0 2011 Design and synthesis of novel amide AKT1 inhibitors with selectivity over CDK2. Amides 30-35 cyclin dependent kinase 2 Homo sapiens 74-78 21570822-0 2011 Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. NU6102 107-113 cyclin dependent kinase 2 Homo sapiens 71-96 21975820-3 2011 The antiproliferative activity of sepiapterin in VEGF-A-treated HUVECs is associated with inhibition of the expression of cyclin-dependent kinases (Cdks) such as Cdk4 and Cdk2. sepiapterin 34-45 cyclin dependent kinase 2 Homo sapiens 148-152 21975820-3 2011 The antiproliferative activity of sepiapterin in VEGF-A-treated HUVECs is associated with inhibition of the expression of cyclin-dependent kinases (Cdks) such as Cdk4 and Cdk2. sepiapterin 34-45 cyclin dependent kinase 2 Homo sapiens 171-175 21599856-3 2011 In the present study, we have made a comprehensive analysis on similarities and differences observed in hydrophobic interactions and hydrogen bond interactions of 170 X-ray crystal structures of active and inactive cyclin-dependent kinase-2 (CDK-2) ligand complexes obtained from the Protein Data Bank. Hydrogen 133-141 cyclin dependent kinase 2 Homo sapiens 215-240 21599856-3 2011 In the present study, we have made a comprehensive analysis on similarities and differences observed in hydrophobic interactions and hydrogen bond interactions of 170 X-ray crystal structures of active and inactive cyclin-dependent kinase-2 (CDK-2) ligand complexes obtained from the Protein Data Bank. Hydrogen 133-141 cyclin dependent kinase 2 Homo sapiens 242-247 21598284-9 2011 Molecular mechanical study of halo derivatives of benzotriazole complexed to cyclin-dependent protein kinase 2 (CDK2) was performed, and MM-PB(GB)SA binding energies were calculated as a case study in finding potent halogenated inhibitors that can serve as antitumor drugs. Halodrol 30-34 cyclin dependent kinase 2 Homo sapiens 77-110 21598284-9 2011 Molecular mechanical study of halo derivatives of benzotriazole complexed to cyclin-dependent protein kinase 2 (CDK2) was performed, and MM-PB(GB)SA binding energies were calculated as a case study in finding potent halogenated inhibitors that can serve as antitumor drugs. benzotriazole 50-63 cyclin dependent kinase 2 Homo sapiens 77-110 21598284-9 2011 Molecular mechanical study of halo derivatives of benzotriazole complexed to cyclin-dependent protein kinase 2 (CDK2) was performed, and MM-PB(GB)SA binding energies were calculated as a case study in finding potent halogenated inhibitors that can serve as antitumor drugs. benzotriazole 50-63 cyclin dependent kinase 2 Homo sapiens 112-116 21598284-9 2011 Molecular mechanical study of halo derivatives of benzotriazole complexed to cyclin-dependent protein kinase 2 (CDK2) was performed, and MM-PB(GB)SA binding energies were calculated as a case study in finding potent halogenated inhibitors that can serve as antitumor drugs. Halodrol 30-34 cyclin dependent kinase 2 Homo sapiens 112-116 21763166-0 2011 Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors. Pyrazoles 36-45 cyclin dependent kinase 2 Homo sapiens 76-101 21763166-0 2011 Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors. pyrimidine 50-60 cyclin dependent kinase 2 Homo sapiens 76-101 21829151-5 2011 Treatment with parthenolide led to G1 phase cell cycle arrest in 5637 cells by modulation of cyclin D1 and phosphorylated cyclin-dependent kinase 2. parthenolide 15-27 cyclin dependent kinase 2 Homo sapiens 122-147 21739974-3 2011 In addition, the 4-acetylantroquinonol B treatment resulted in the decreases of CDK2 and CDK4, and an increase of p27 in a dose-dependent manner. 4-acetylantroquinonol B 17-40 cyclin dependent kinase 2 Homo sapiens 80-84 21575631-0 2011 Sustained activation of ERK and Cdk2/cyclin-A signaling pathway by pemetrexed leading to S-phase arrest and apoptosis in human non-small cell lung cancer A549 cells. Pemetrexed 67-77 cyclin dependent kinase 2 Homo sapiens 32-36 21556037-3 2011 Here we report that miR-376a participates in the regulation of the early stages of human erythropoiesis by targeting cyclin-dependent kinase 2 (CDK2) and Argonaute 2 (Ago2). mir-376a 20-28 cyclin dependent kinase 2 Homo sapiens 117-142 21556037-3 2011 Here we report that miR-376a participates in the regulation of the early stages of human erythropoiesis by targeting cyclin-dependent kinase 2 (CDK2) and Argonaute 2 (Ago2). mir-376a 20-28 cyclin dependent kinase 2 Homo sapiens 144-148 21575631-2 2011 In this study, we show that inducing cell cycle S-phase arrest and apoptosis in human lung adenocarcinoma A549 cells with pemetrexed is associated with increased cyclin-A and cyclin-dependent kinase 2 (Cdk2) protein and Cdk2/cyclin-A kinase activity. Pemetrexed 122-132 cyclin dependent kinase 2 Homo sapiens 175-200 21575631-5 2011 Knockdown of ERK1/2 using specific siRNA, as well as known inhibitors (PD98059 and U0126), effectively suppressed the expression of cyclin-A and Cdk2, and reduced S-phase arrest and apoptosis induced by pemetrexed. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 71-78 cyclin dependent kinase 2 Homo sapiens 145-149 21575631-5 2011 Knockdown of ERK1/2 using specific siRNA, as well as known inhibitors (PD98059 and U0126), effectively suppressed the expression of cyclin-A and Cdk2, and reduced S-phase arrest and apoptosis induced by pemetrexed. U 0126 83-88 cyclin dependent kinase 2 Homo sapiens 145-149 21575631-2 2011 In this study, we show that inducing cell cycle S-phase arrest and apoptosis in human lung adenocarcinoma A549 cells with pemetrexed is associated with increased cyclin-A and cyclin-dependent kinase 2 (Cdk2) protein and Cdk2/cyclin-A kinase activity. Pemetrexed 122-132 cyclin dependent kinase 2 Homo sapiens 202-206 21575631-6 2011 These data provide the first evidence that pemetrexed-induced S-phase arrest and apoptosis is associated with an increase in Cdk2 and cyclin-A expression and activation, which is ERK-dependent and upstream of caspase-3. Pemetrexed 43-53 cyclin dependent kinase 2 Homo sapiens 125-129 21575631-2 2011 In this study, we show that inducing cell cycle S-phase arrest and apoptosis in human lung adenocarcinoma A549 cells with pemetrexed is associated with increased cyclin-A and cyclin-dependent kinase 2 (Cdk2) protein and Cdk2/cyclin-A kinase activity. Pemetrexed 122-132 cyclin dependent kinase 2 Homo sapiens 220-224 21575631-7 2011 Our findings suggest that the ERK-mediated Cdk2/cyclin-A signaling pathway is an important regulator of pemetrexed-induced S-phase arrest and apoptotic cell death. Pemetrexed 104-114 cyclin dependent kinase 2 Homo sapiens 43-47 21575631-3 2011 Knockdown of cyclin-A using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced S-phase arrest and apoptosis. alvocidib 93-105 cyclin dependent kinase 2 Homo sapiens 74-78 21730979-3 2011 As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 3-9 cyclin dependent kinase 2 Homo sapiens 37-41 21592546-5 2011 RESULTS: Cisplatin consistently induced transient S-phase arrest by inhibiting Cdk2/cyclin A complex in S-phase at 12 h and then a durable G2/M-arrest by inhibiting Cdc2/cyclin B complex at 12-18 h. These inhibitions were associated with Chk1 and Chk2 activation and resultant increase in inhibitory tyrosine phosphorylation of Cdk2 and Cdc2. Cisplatin 9-18 cyclin dependent kinase 2 Homo sapiens 328-332 21592546-6 2011 Cisplatin also potently inhibited G1-phase Cdk4/cyclin D1 and Cdk2/cyclin E activities at ~18 h. In agreement, exposure of cisplatin-treated A2780, HCT-116(p53-/-) and HCT-116(p21-/-) tumor cells to nocodazole revealed limited G1-arrest that was dependent on p53 and p21. Cisplatin 0-9 cyclin dependent kinase 2 Homo sapiens 62-66 21592546-6 2011 Cisplatin also potently inhibited G1-phase Cdk4/cyclin D1 and Cdk2/cyclin E activities at ~18 h. In agreement, exposure of cisplatin-treated A2780, HCT-116(p53-/-) and HCT-116(p21-/-) tumor cells to nocodazole revealed limited G1-arrest that was dependent on p53 and p21. Cisplatin 123-132 cyclin dependent kinase 2 Homo sapiens 62-66 21592546-5 2011 RESULTS: Cisplatin consistently induced transient S-phase arrest by inhibiting Cdk2/cyclin A complex in S-phase at 12 h and then a durable G2/M-arrest by inhibiting Cdc2/cyclin B complex at 12-18 h. These inhibitions were associated with Chk1 and Chk2 activation and resultant increase in inhibitory tyrosine phosphorylation of Cdk2 and Cdc2. Cisplatin 9-18 cyclin dependent kinase 2 Homo sapiens 79-83 21550420-2 2011 In reporter gene assays, cyclin A2 overexpression enhanced PR activity while inhibition of Cdk2 activity using the chemical inhibitor roscovitine or Cdk2 siRNA strongly inhibited PR activity. Roscovitine 134-145 cyclin dependent kinase 2 Homo sapiens 91-95 21550420-6 2011 We show that one of these sites, T1426 (adjacent to the C-terminal LXXLL nuclear receptor interaction motif), is an in vivo target of Cdks in mammalian cells and an in vitro target of Cdk1 and Cdk2. 1,4,7,10-Tetraazacyclododecane tetrahydrochloride 33-38 cyclin dependent kinase 2 Homo sapiens 193-197 21730979-3 2011 As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 3-9 cyclin dependent kinase 2 Homo sapiens 80-84 21730979-3 2011 As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. Cisplatin 65-74 cyclin dependent kinase 2 Homo sapiens 80-84 24900361-3 2011 A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC50 values of ca. aigialomycin D 96-110 cyclin dependent kinase 2 Homo sapiens 60-64 21684737-0 2011 Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors. 2-aminopyrimidine 30-48 cyclin dependent kinase 2 Homo sapiens 61-65 21726525-5 2011 Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G(0)/G(1) phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone 10-27 cyclin dependent kinase 2 Homo sapiens 304-311 24900361-3 2011 A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC50 values of ca. aigialomycin D 96-110 cyclin dependent kinase 2 Homo sapiens 148-152 21684737-2 2011 Substitution with pyrrolidine-3,4-diol at the 4-position of phenol provided potent inhibitory activity against CDK1 and CDK2. Pyrrolidine-3,4-diol 18-38 cyclin dependent kinase 2 Homo sapiens 120-124 21391976-10 2011 Using a cellular kinome array and an in vitro CDK panel, we found that roscovitine inhibited protein kinase A, ribosomal S6 kinase and CDKs 2, 5, 7 and 9. Roscovitine 71-82 cyclin dependent kinase 2 Homo sapiens 111-153 21684737-2 2011 Substitution with pyrrolidine-3,4-diol at the 4-position of phenol provided potent inhibitory activity against CDK1 and CDK2. Phenol 60-66 cyclin dependent kinase 2 Homo sapiens 120-124 21483429-9 2011 Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27(Kip1) and p57(Kip2). Sertraline 8-18 cyclin dependent kinase 2 Homo sapiens 122-147 21215801-5 2011 These CSs also induced cell apoptosis by increasing the concentration of intracellular free calcium ([Ca(2+)](i)) and induced S phase cell cycle arrest by down-regulating the expression of Cyclin A, cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) as well as up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21(CIP1)). Cardiac Glycosides 6-9 cyclin dependent kinase 2 Homo sapiens 199-224 21215801-5 2011 These CSs also induced cell apoptosis by increasing the concentration of intracellular free calcium ([Ca(2+)](i)) and induced S phase cell cycle arrest by down-regulating the expression of Cyclin A, cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) as well as up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21(CIP1)). Cardiac Glycosides 6-9 cyclin dependent kinase 2 Homo sapiens 226-230 21483429-9 2011 Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27(Kip1) and p57(Kip2). Sertraline 8-18 cyclin dependent kinase 2 Homo sapiens 149-153 21886895-0 2011 Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine CDK2 Inhibitors as Anti-Tumor Agents. PYRIMIDO[4,5-D]PYRIMIDINE 53-78 cyclin dependent kinase 2 Homo sapiens 79-83 21822799-0 2011 Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis. Paclitaxel 67-77 cyclin dependent kinase 2 Homo sapiens 0-4 21822799-2 2011 Here we demonstrate that the upregulation of cyclin-dependent kinase 2 (Cdk2) activity coincides with the loss of mitochondrial membrane potential (MMP) in paclitaxel-induced apoptosis. Paclitaxel 156-166 cyclin dependent kinase 2 Homo sapiens 45-70 21822799-2 2011 Here we demonstrate that the upregulation of cyclin-dependent kinase 2 (Cdk2) activity coincides with the loss of mitochondrial membrane potential (MMP) in paclitaxel-induced apoptosis. Paclitaxel 156-166 cyclin dependent kinase 2 Homo sapiens 72-76 21822799-3 2011 Ectopic expression of the dominant negative Cdk2 (Cdk2-dn) and a specific Cdk2 inhibitor, p21( WAF1/CIP1 ), effectively suppresses the loss of MMP, the release of cytochrome c, and subsequent activation of caspase-3 in paclitaxel-treated cells. Paclitaxel 219-229 cyclin dependent kinase 2 Homo sapiens 44-48 21822799-3 2011 Ectopic expression of the dominant negative Cdk2 (Cdk2-dn) and a specific Cdk2 inhibitor, p21( WAF1/CIP1 ), effectively suppresses the loss of MMP, the release of cytochrome c, and subsequent activation of caspase-3 in paclitaxel-treated cells. Paclitaxel 219-229 cyclin dependent kinase 2 Homo sapiens 50-54 21822799-3 2011 Ectopic expression of the dominant negative Cdk2 (Cdk2-dn) and a specific Cdk2 inhibitor, p21( WAF1/CIP1 ), effectively suppresses the loss of MMP, the release of cytochrome c, and subsequent activation of caspase-3 in paclitaxel-treated cells. Paclitaxel 219-229 cyclin dependent kinase 2 Homo sapiens 50-54 21886895-1 2011 A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine 12-58 cyclin dependent kinase 2 Homo sapiens 84-88 21411497-0 2011 Nitrite-mediated modulation of HL-60 cell cycle and proliferation: involvement of cyclin-dependent kinase 2 activation. Nitrites 0-7 cyclin dependent kinase 2 Homo sapiens 82-107 21373746-5 2011 Following PTX-2 treatment of synovial fibroblasts, an increased binding of p21 with Cdk2 and Cdk6 was paralleled by a significant decrease in retinoblastoma protein (pRB) phosphorylation and in the protein levels of E2F transcription factors. pectenotoxin 2 10-15 cyclin dependent kinase 2 Homo sapiens 84-88 21411497-11 2011 Indeed proliferative effect of nitrite was blocked by roscovitine, a Cdk2 inhibitor. Nitrites 31-38 cyclin dependent kinase 2 Homo sapiens 69-73 21411497-11 2011 Indeed proliferative effect of nitrite was blocked by roscovitine, a Cdk2 inhibitor. Roscovitine 54-65 cyclin dependent kinase 2 Homo sapiens 69-73 21411497-12 2011 The results obtained demonstrate that the proliferative effect of nitrite on HL-60 cells seems to be NO-mediated, redox-sensitive, and Cdk2 activation-dependent, warranting detailed studies before initiating its clinical use. Nitrites 66-73 cyclin dependent kinase 2 Homo sapiens 135-139 21620802-5 2011 The SUAM-14746-induced growth inhibition in NB-1 cells was associated with pronounced G(0)/G(1) arrest and reduced levels of phosphorylated retinoblastoma protein (pRb), cyclin E, and cyclin dependent kinase (CDK) 2, and increased levels of the CDK inhibitor p27(kip1) and the tumor suppressor p53. 3-((4-(2-styrylphenoxy)butanoyl)-4-hydroxyprolyl)thiazolidine 4-14 cyclin dependent kinase 2 Homo sapiens 184-215 21376716-6 2011 In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Rosiglitazone 172-185 cyclin dependent kinase 2 Homo sapiens 125-129 21565702-0 2011 Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis. Magnesium 67-76 cyclin dependent kinase 2 Homo sapiens 117-121 21291269-5 2011 In an effort to identify potential target sites for disruption of the CDK-cyclin interaction, we probed the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS) with human CDK2 and cyclin A using fluorescence spectroscopy and protein crystallography. 8-anilino-1-naphthalenesulfonic acid 130-163 cyclin dependent kinase 2 Homo sapiens 181-185 21291269-5 2011 In an effort to identify potential target sites for disruption of the CDK-cyclin interaction, we probed the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS) with human CDK2 and cyclin A using fluorescence spectroscopy and protein crystallography. 8-anilino-1-naphthalenesulfonic acid 165-168 cyclin dependent kinase 2 Homo sapiens 181-185 21291269-6 2011 ANS interacts with free CDK2 in a saturation-dependent manner with an apparent K(d) of 37 muM, and cyclin A displaced ANS from CDK2 with an EC(50) value of 0.6 muM. 8-anilino-1-naphthalenesulfonic acid 0-3 cyclin dependent kinase 2 Homo sapiens 24-28 21291269-6 2011 ANS interacts with free CDK2 in a saturation-dependent manner with an apparent K(d) of 37 muM, and cyclin A displaced ANS from CDK2 with an EC(50) value of 0.6 muM. 8-anilino-1-naphthalenesulfonic acid 118-121 cyclin dependent kinase 2 Homo sapiens 127-131 21291269-8 2011 Binding of ANS is accompanied by substantial structural changes in CDK2, resulting in a C-helix conformation that is incompatible for cyclin A association. 8-anilino-1-naphthalenesulfonic acid 11-14 cyclin dependent kinase 2 Homo sapiens 67-71 21291269-9 2011 These findings indicate the potential of the ANS binding pocket as a new target site for allosteric inhibitors disrupting the interaction of CDKs and cyclins. 8-anilino-1-naphthalenesulfonic acid 45-48 cyclin dependent kinase 2 Homo sapiens 141-145 21565702-1 2011 We have determined high-resolution crystal structures of a CDK2/Cyclin A transition state complex bound to ADP, substrate peptide, and MgF(3)(-). Adenosine Diphosphate 107-110 cyclin dependent kinase 2 Homo sapiens 59-63 21565702-2 2011 Compared to previous structures of active CDK2, the catalytic subunit of the kinase adopts a more closed conformation around the active site and now allows observation of a second Mg(2+) ion in the active site. magnesium ion 180-186 cyclin dependent kinase 2 Homo sapiens 42-46 21565702-3 2011 Coupled with a strong [Mg(2+)] effect on in vitro kinase activity, the structures suggest that the transient binding of the second Mg(2+) ion is necessary to achieve maximum rate enhancement of the chemical reaction, and Mg(2+) concentration could represent an important regulator of CDK2 activity in vivo. magnesium ion 23-29 cyclin dependent kinase 2 Homo sapiens 284-288 21565702-3 2011 Coupled with a strong [Mg(2+)] effect on in vitro kinase activity, the structures suggest that the transient binding of the second Mg(2+) ion is necessary to achieve maximum rate enhancement of the chemical reaction, and Mg(2+) concentration could represent an important regulator of CDK2 activity in vivo. magnesium ion 131-137 cyclin dependent kinase 2 Homo sapiens 284-288 21565702-3 2011 Coupled with a strong [Mg(2+)] effect on in vitro kinase activity, the structures suggest that the transient binding of the second Mg(2+) ion is necessary to achieve maximum rate enhancement of the chemical reaction, and Mg(2+) concentration could represent an important regulator of CDK2 activity in vivo. magnesium ion 131-137 cyclin dependent kinase 2 Homo sapiens 284-288 21258042-0 2011 6,7,4"-trihydroxyisoflavone inhibits HCT-116 human colon cancer cell proliferation by targeting CDK1 and CDK2. 6,7,4'-trihydroxyisoflavone 0-27 cyclin dependent kinase 2 Homo sapiens 105-109 21325496-0 2011 Cdk2-dependent phosphorylation of p21 regulates the role of Cdk2 in cisplatin cytotoxicity. Cisplatin 68-77 cyclin dependent kinase 2 Homo sapiens 0-4 21325496-0 2011 Cdk2-dependent phosphorylation of p21 regulates the role of Cdk2 in cisplatin cytotoxicity. Cisplatin 68-77 cyclin dependent kinase 2 Homo sapiens 60-64 21325496-1 2011 Cisplatin cytotoxicity is dependent on cyclin-dependent kinase 2 (Cdk2) activity in vivo and in vitro. Cisplatin 0-9 cyclin dependent kinase 2 Homo sapiens 39-64 21325496-1 2011 Cisplatin cytotoxicity is dependent on cyclin-dependent kinase 2 (Cdk2) activity in vivo and in vitro. Cisplatin 0-9 cyclin dependent kinase 2 Homo sapiens 66-70 21325496-2 2011 We found that an 18-kDa protein identified by mass spectrometry as p21(WAF1/Cip1) was phosphorylated by Cdk2 starting 12 h after cisplatin exposure. Cisplatin 129-138 cyclin dependent kinase 2 Homo sapiens 104-108 21325496-4 2011 The adenoviral transduction of p21 before cisplatin exposure protects from cytotoxicity by inhibiting Cdk2. Cisplatin 42-51 cyclin dependent kinase 2 Homo sapiens 102-106 21325496-9 2011 We conclude that phosphorylation of p21 by Cdk2 limits the effectiveness of p21 to inhibit Cdk2, which is the mechanism for continued cisplatin cytotoxicity even after the induction of a protective protein. Cisplatin 134-143 cyclin dependent kinase 2 Homo sapiens 43-47 21325496-9 2011 We conclude that phosphorylation of p21 by Cdk2 limits the effectiveness of p21 to inhibit Cdk2, which is the mechanism for continued cisplatin cytotoxicity even after the induction of a protective protein. Cisplatin 134-143 cyclin dependent kinase 2 Homo sapiens 91-95 21262353-2 2011 Here we show that Cdk2 present in hepatic endosome fractions is strictly located in a Triton X-100-resistant environment. Octoxynol 86-98 cyclin dependent kinase 2 Homo sapiens 18-22 21421237-6 2011 Costunolide induced G1-phase cell cycle arrest, which was supported by p21 up-regulation and its association with the cyclin dependent kinase 2/cyclin E complex. costunolide 0-11 cyclin dependent kinase 2 Homo sapiens 118-143 21421237-11 2011 The association of p21 with the cyclin dependent kinase 2/cyclin E complex blocks cyclin dependent kinase 2 activity and inhibits Rb phosphorylation, leading to G1 arrest of the cell cycle and subsequent apoptotic cell death in human prostate cancer cells. Rubidium 130-132 cyclin dependent kinase 2 Homo sapiens 32-57 21321187-7 2011 MG treatment of VSMCs led to increased DNA synthesis (EC(50)=5.8 muM), cell proliferation, phosphorylation of p21 and glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta), and increased cyclin-dependent kinase 2 (CDK2) activity. vsmcs 16-21 cyclin dependent kinase 2 Homo sapiens 188-213 21321187-7 2011 MG treatment of VSMCs led to increased DNA synthesis (EC(50)=5.8 muM), cell proliferation, phosphorylation of p21 and glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta), and increased cyclin-dependent kinase 2 (CDK2) activity. vsmcs 16-21 cyclin dependent kinase 2 Homo sapiens 215-219 21417417-2 2011 Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 3aH-pyrazolo[4,3-d]pyrimidine 39-64 cyclin dependent kinase 2 Homo sapiens 19-23 21417417-4 2011 An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Roscovitine 120-131 cyclin dependent kinase 2 Homo sapiens 50-54 21483720-9 2011 Twelve of the most potent hits had an azapurine core with structure activity relationship (SAR) analysis identifying the functional groups on the 2 and 9 positions as essential for CRK3:CYC6 inhibition and specificity against CDK2:CycA. Imidazotriazine 38-47 cyclin dependent kinase 2 Homo sapiens 226-230 21941773-4 2011 The exposure to silica resulted in the increasing protein expression levels of CyclinE and CDK2 in negative control cells, and the expression levels of CyclinE were obviously suppressed in H-Ku80 and H-PKcs as compared with control cells. Silicon Dioxide 16-22 cyclin dependent kinase 2 Homo sapiens 91-95 21308739-6 2011 Exposure of MCF-7 cells to ROSC abolished the activating phosphorylation of CDK2 and CDK7 at Ser(164/170). Serine 93-96 cyclin dependent kinase 2 Homo sapiens 76-80 20702488-8 2011 Antiproliferative effect after treatment with TXL was assessed by determination of the protein levels of p21, cyclinD1, PCNA, and cdk-2, which are the key regulators for cell cycle progression. Docetaxel 46-49 cyclin dependent kinase 2 Homo sapiens 130-135 21119048-9 2011 In a mechanistic study employing T47D cells we found that CDB-4124 suppressed G(1)/G(0)-S transition by inhibiting CDK2 and CDK4 expressions, which correlated with inhibition of estrogen receptor (ER) expression. cdb- 58-62 cyclin dependent kinase 2 Homo sapiens 115-119 20839231-5 2011 Cd-induced cell-cycle arrest was associated with a decrease in CDK2 protein and with increase in p21 expression and p53 phosphorylation. Cadmium 0-2 cyclin dependent kinase 2 Homo sapiens 63-67 21941773-0 2011 [Roles of DNA dependent protein kinase in silica-induced cyclin E and CDK2 expressions and cell cycle changes in human embryo lung fibroblasts]. Silicon Dioxide 42-48 cyclin dependent kinase 2 Homo sapiens 70-74 21941773-1 2011 OBJECTIVE: To study the roles of DNA dependent protein kinase (DNA-PK)in silica-induced cell cycle changes and expressions of CyclinE and CDK2 in human embryo lung fibroblasts (HELF). Silicon Dioxide 73-79 cyclin dependent kinase 2 Homo sapiens 138-142 21941773-3 2011 Flow cytometry was used to detect the distributions of cell cycle and western blot assay was used to determine the expression levels of CyclinE and CDK2 after cells were exposed to 200 microg/ml silica for 0, 3, 6, 12, 24 h. RESULTS: The proportion of G1 phases in negative control cells decreased from 83.53% +/- 2.24% to 69.11% +/- 3.12% after exposure to silica; the proportion of G1 phases in H-Ku80 and H-PKcs cells exposed to silica decreased from 85.16% +/- 3.73% to 59.92% +/- 3.31% and from 75.06% +/- 2.23% to 58.32% +/- 1.35%, respectively (P < 0.05). Silicon Dioxide 195-201 cyclin dependent kinase 2 Homo sapiens 148-152 21439087-6 2011 To investigate the effects of HMBA on protein localization and the activities of GSK-3beta, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. hexamethylene bisacetamide 30-34 cyclin dependent kinase 2 Homo sapiens 92-96 21305681-0 2011 The chemoselective one-step alkylation and isolation of thiophosphorylated cdk2 substrates in the presence of native cysteine. Cysteine 117-125 cyclin dependent kinase 2 Homo sapiens 75-79 20839231-6 2011 Cd treatment caused a distinct increase in the formation of p21-cyclin E-CDK2 complex, as revealed by immunoprecipitation. Cadmium 0-2 cyclin dependent kinase 2 Homo sapiens 73-77 21212792-5 2011 At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibited the expression of CDK2 and CDK9 and dephosphorylated CDK7. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 24-31 cyclin dependent kinase 2 Homo sapiens 148-152 21328450-4 2011 Exposure of MCF-7 cells to ROSC abolished the activating phosphorylation of CDK2 and CDK7 in a concentration and time-dependent manner. Roscovitine 27-31 cyclin dependent kinase 2 Homo sapiens 76-80 21286784-1 2011 A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. pm6-dh2 35-42 cyclin dependent kinase 2 Homo sapiens 158-162 21209116-5 2011 This screening identified roscovitine, a selective inhibitor of cyclin-dependent kinase 1 (CDK1), CDK2, CDK5, and CDK7. Roscovitine 26-37 cyclin dependent kinase 2 Homo sapiens 98-102 21384303-4 2011 Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. bmc 204-207 cyclin dependent kinase 2 Homo sapiens 157-161 21278485-3 2011 Recently, we and others demonstrate that CDK1 and CDK2 phosphorylate EZH2 at threonine 350 (T350) and that T350 phosphorylation is important for the binding of EZH2 to PRC2 recruiters, such as noncoding RNAs (ncRNAs) HOTAIR and XIST, and for the effective recruitment of PRC2 to EZH2 target loci in cells. Threonine 77-86 cyclin dependent kinase 2 Homo sapiens 50-54 22355233-0 2011 Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors. phenetheren 49-60 cyclin dependent kinase 2 Homo sapiens 122-126 21148318-7 2011 RBP1 is phosphorylated by CDK2 on serines 864 and 1007, which are N- and C-terminal to the LXCXE motif, respectively. Serine 34-41 cyclin dependent kinase 2 Homo sapiens 26-30 21148318-7 2011 RBP1 is phosphorylated by CDK2 on serines 864 and 1007, which are N- and C-terminal to the LXCXE motif, respectively. lxcxe 91-96 cyclin dependent kinase 2 Homo sapiens 26-30 21217199-4 2011 Here we compare the cyclins A and E CLSs at the structural and functional levels and identify a new cyclin A CLS mutant that disrupts all CLS functions and reduces the affinity of cyclin A for Cdk2. Chlorine 109-112 cyclin dependent kinase 2 Homo sapiens 193-197 21217199-5 2011 Analysis of interactions of the CLS motif within the cyclin molecules highlights the importance of the cyclin CBOX1 region for Cdk2 binding. Chlorine 32-35 cyclin dependent kinase 2 Homo sapiens 127-131 22355233-2 2011 Recent studies have revealed two new aristolactames (compound A and B) with gamma-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). gamma-lactame 76-89 cyclin dependent kinase 2 Homo sapiens 159-184 22355233-2 2011 Recent studies have revealed two new aristolactames (compound A and B) with gamma-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). gamma-lactame 76-89 cyclin dependent kinase 2 Homo sapiens 186-190 22355233-2 2011 Recent studies have revealed two new aristolactames (compound A and B) with gamma-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). phenentherene 110-123 cyclin dependent kinase 2 Homo sapiens 159-184 22355233-2 2011 Recent studies have revealed two new aristolactames (compound A and B) with gamma-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). phenentherene 110-123 cyclin dependent kinase 2 Homo sapiens 186-190 21685708-5 2011 Docetaxel also decreased the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK) 2, cyclin E, CDK4, cyclin D1, retinoblastoma protein, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Docetaxel 0-9 cyclin dependent kinase 2 Homo sapiens 83-114 20688159-5 2011 Cycloheximide decay assays showed that Akt2 increased the stability and nuclear localization of p27, thus inhibiting the cyclin E/CDK2 complex. Cycloheximide 0-13 cyclin dependent kinase 2 Homo sapiens 130-134 21275261-8 2011 Furthermore, C-1305 increased phosphorylation of pRb protein and CDK2 at Thr160 in HL60 cells, but not in MCF-7 cells. C 1305 13-19 cyclin dependent kinase 2 Homo sapiens 65-69 21800645-4 2011 Moreover, the expression level of cyclin-dependent kinase-2 as well as cyclin A2, D3 and E2 mRNAs is significantly decreased under glucose or glutamine deprivation conditions both in control and endoplasmic reticulum-nuclei-1-deficient glioma cells. Glucose 131-138 cyclin dependent kinase 2 Homo sapiens 34-59 21720559-5 2011 At the molecular level, honokiol markedly decreased the expression of cyclins (D1 and E) and cyclin-dependent kinases (Cdk2 and Cdk4), and caused an increase in Cdk inhibitors, p21 and p27. honokiol 24-32 cyclin dependent kinase 2 Homo sapiens 119-123 21800645-4 2011 Moreover, the expression level of cyclin-dependent kinase-2 as well as cyclin A2, D3 and E2 mRNAs is significantly decreased under glucose or glutamine deprivation conditions both in control and endoplasmic reticulum-nuclei-1-deficient glioma cells. Glutamine 142-151 cyclin dependent kinase 2 Homo sapiens 34-59 21082766-3 2010 The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. CHEMBL1630460 52-87 cyclin dependent kinase 2 Homo sapiens 186-190 21080703-3 2010 Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC50= 3, 30, 30, 250, and 90 nmol/L, respectively). pyrazolo(1,5-a)pyrimidine 40-65 cyclin dependent kinase 2 Homo sapiens 153-157 21082766-3 2010 The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. (5Z)-5-(4-Hydroxybenzylidene)-2,4-imidazolidinedione 99-124 cyclin dependent kinase 2 Homo sapiens 186-190 20970954-6 2010 Butyrate"s cooperative effects on H3-Lysine9 acetylation and H3-Serine10 phosphorylation, and contrasting effects on di-methylation of H3-Lysine9 and H3-Lysine4 suggests that the interplay between these site-specific modifications cause distinct chromatin alterations that allow cyclin D1 and D3 induction, G1-specific cdk4, cdk6 and cdk2 downregulation, and upregulation of cdk inhibitors, p15INK4b and p21Cip1. Butyrates 0-8 cyclin dependent kinase 2 Homo sapiens 334-338 20149834-2 2010 In this study, we applied a phospho-proteomic technique to screen target molecules of Cdk2 during etoposide-induced apoptosis. Etoposide 98-107 cyclin dependent kinase 2 Homo sapiens 86-90 20149834-5 2010 The cellular levels of these phosphoproteins were markedly reduced in the presence of etoposide in HeLa cells transfected with dominant negative mutant construct of Cdk2. Etoposide 86-95 cyclin dependent kinase 2 Homo sapiens 165-169 20149834-6 2010 Among the six candidate phosphoproteins, human triosephosphate isomerase (TPI), a glycolytic enzyme, was found to be a direct substrate of Cdk2 during etoposide-induced apoptosis. Etoposide 151-160 cyclin dependent kinase 2 Homo sapiens 139-143 20149834-9 2010 Such phosphorylation of TPI and a subsequent decrease in its enzyme activity were prevented by treatment with olomoucine, a specific inhibitor of Cdk2. olomoucine 110-120 cyclin dependent kinase 2 Homo sapiens 146-150 21104938-6 2010 The combined treatment of FNQ with AG1478 (a specific EGFR inhibitor) significantly enhanced the G(2)/M arrest and apoptosis, and also led to up-regulation in Bax, p53, p21, p27, release of mitochondrial cytochrome c, and down-regulation of Bcl-2, XIAP, survivin, cyclin A, cyclin B, Cdk1, and Cdk2 in A549 cells. furano-1,2-naphthoquinone 26-29 cyclin dependent kinase 2 Homo sapiens 294-298 20822897-1 2010 AIM: Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells. Roscovitine 22-32 cyclin dependent kinase 2 Homo sapiens 74-109 21182779-7 2010 SMIPs (small molecule inhibitors of p27 depletion) also upregulate p21(Cip)1, inhibit cellular CDK2 activity, induce G1 delay, inhibit colony formation in soft agar and exhibit preferential cytotoxicity in LNCaP cells relative to normal human fibroblasts. smips 0-5 cyclin dependent kinase 2 Homo sapiens 95-99 21104938-6 2010 The combined treatment of FNQ with AG1478 (a specific EGFR inhibitor) significantly enhanced the G(2)/M arrest and apoptosis, and also led to up-regulation in Bax, p53, p21, p27, release of mitochondrial cytochrome c, and down-regulation of Bcl-2, XIAP, survivin, cyclin A, cyclin B, Cdk1, and Cdk2 in A549 cells. RTKI cpd 35-41 cyclin dependent kinase 2 Homo sapiens 294-298 21099355-9 2010 A genetic interaction with the DNA damage checkpoint was demonstrated by showing an increased toxicity of hCdk2 and Ime2 in RAD53-deleted cells, and delayed Rad53 activation in response to MMS treatment in cells overexpressing hCdk2 or Ime2. Methyl Methanesulfonate 189-192 cyclin dependent kinase 2 Homo sapiens 227-232 20822897-1 2010 AIM: Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells. Roscovitine 42-55 cyclin dependent kinase 2 Homo sapiens 74-109 21042722-5 2010 DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Methylcholanthrene 38-40 cyclin dependent kinase 2 Homo sapiens 144-148 20225320-6 2010 Concurrently, CPX downregulated cellular protein expression of cyclins (A, B1, D1 and E) and cyclin-dependent kinases (CDK2 and CDK4) and upregulated expression of the CDK inhibitor p21(Cip1), leading to hypophosphorylation of retinoblastoma protein. Ciclopirox 14-17 cyclin dependent kinase 2 Homo sapiens 119-123 20661261-5 2010 We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor beta (PDGFRbeta)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. baicalin 18-26 cyclin dependent kinase 2 Homo sapiens 95-99 20869873-0 2010 3D-QSAR and docking studies on pyrazolo[4,3-h]qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors. pyrazolo[4,3-h]qinazoline-3-carboxamides 31-71 cyclin dependent kinase 2 Homo sapiens 102-106 20869873-1 2010 3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. pyrazolo[4,3-h]quinazoline-3-carboxamides 58-99 cyclin dependent kinase 2 Homo sapiens 103-107 20869873-0 2010 3D-QSAR and docking studies on pyrazolo[4,3-h]qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors. pyrazolo[4,3-h]qinazoline-3-carboxamides 31-71 cyclin dependent kinase 2 Homo sapiens 75-100 20661261-8 2010 Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRbeta-ERK1/2 signaling cascade. baicalin 55-63 cyclin dependent kinase 2 Homo sapiens 254-258 20540935-6 2010 Cells were arrested in G(0)/G(1) phase followed by the induction of apoptosis after treatment of troglitazone with concomitant decrease in the expression of the G(0)/G(1) phase regulatory proteins; Cdk2, Cdk4, cyclin B1, D1, and E as well as in the anti-apoptosis protein Bcl-2 along with an increase in the expression of the pro-apoptosis-associated proteins; Caspase-3, Caspase-9 and Bax. Troglitazone 97-109 cyclin dependent kinase 2 Homo sapiens 198-202 20878096-12 2010 Protein expression levels of cell cycle regulating proteins CDK1, CDK2, CDK4, cyclin D1, cyclin E, p19 and p27 were markedly altered by simvastatin. Simvastatin 136-147 cyclin dependent kinase 2 Homo sapiens 66-70 20850841-3 2010 RESULTS: As expected, roscovitine caused dose and time dependent inhibition of cyclin dependent kinase 2 autophosphorylation, and of cyclin dependent kinase mediated Pol II phosphorylation in the ACHN (p53-wt) and 786-O (p53 inactive) renal cell carcinoma cell lines (ATCC ). Roscovitine 22-33 cyclin dependent kinase 2 Homo sapiens 79-104 20484412-11 2010 The kinase cyclin-dependent kinase 2 is activated after progesterone treatment and could catalyze progesterone-induced phosphorylation of histone H1 by chromatin remodeling complexes. Progesterone 56-68 cyclin dependent kinase 2 Homo sapiens 11-36 20484412-11 2010 The kinase cyclin-dependent kinase 2 is activated after progesterone treatment and could catalyze progesterone-induced phosphorylation of histone H1 by chromatin remodeling complexes. Progesterone 98-110 cyclin dependent kinase 2 Homo sapiens 11-36 20935635-3 2010 Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Threonine 150-153 cyclin dependent kinase 2 Homo sapiens 95-120 20935635-3 2010 Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Threonine 150-153 cyclin dependent kinase 2 Homo sapiens 122-126 20832307-1 2010 A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). pyrazolobenzodiazepines 18-41 cyclin dependent kinase 2 Homo sapiens 88-113 20832307-1 2010 A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). pyrazolobenzodiazepines 18-41 cyclin dependent kinase 2 Homo sapiens 115-119 20669973-7 2010 Although 17-AAG downregulated cyclin D1, cyclin E, CDK4 and CDK6, it led to cyclin A and CDK2 accumulation, which was reversed by the addition of U0126. U 0126 146-151 cyclin dependent kinase 2 Homo sapiens 89-93 21152296-0 2010 Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking. 4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline 30-72 cyclin dependent kinase 2 Homo sapiens 95-99 20811155-4 2010 Here, we have shown that one key determinant of cisplatin-resistance in testicular embryonal carcinoma (EC) is high cytoplasmic expression of the cyclin-dependent kinase (CDK) inhibitor p21. Cisplatin 48-57 cyclin dependent kinase 2 Homo sapiens 171-174 20811155-5 2010 The EC component of the majority of refractory testicular cancer patients exhibited high cytoplasmic p21 expression, which protected EC cell lines against cisplatin-induced apoptosis via CDK2 inhibition. Cisplatin 155-164 cyclin dependent kinase 2 Homo sapiens 187-191 21152296-2 2010 A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. 4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline 211-252 cyclin dependent kinase 2 Homo sapiens 275-279 20851342-4 2010 The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. Dichlororibofuranosylbenzimidazole 56-59 cyclin dependent kinase 2 Homo sapiens 35-39 20851342-4 2010 The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. Dichlororibofuranosylbenzimidazole 111-114 cyclin dependent kinase 2 Homo sapiens 35-39 20808948-5 2010 Staurosporine, as well as three other inhibitors of protein kinases (cdk2, Pim-1 and casein kinase type 2), effectively bound to synapsin I with nanomolar affinities and promoted synapsin-induced F-actin bundling. Staurosporine 0-13 cyclin dependent kinase 2 Homo sapiens 69-73 20647328-4 2010 We find that Urso-Aspirin combination reduces the risk of adenocarcinoma in vivo in animals with reflux, decreases the proliferation of esophageal adenocarcinoma cells, and downregulates a key cell cycle regulator, CDK2. urso-aspirin 13-25 cyclin dependent kinase 2 Homo sapiens 215-219 20647328-7 2010 Although the Urso-Aspirin combination downregulates GLI1, the GLI1 overexpression not only abrogates the effect of this combination on proliferation but it also restores CDK-2 expression. urso-aspirin 13-25 cyclin dependent kinase 2 Homo sapiens 170-175 20647328-8 2010 These findings support that the chemopreventive effect of the Urso-Aspirin combination occurs, at least in part, through a novel GLI1-CDK2-dependent mechanism. urso-aspirin 62-74 cyclin dependent kinase 2 Homo sapiens 134-138 20647328-10 2010 Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin. Ursodeoxycholic Acid 173-177 cyclin dependent kinase 2 Homo sapiens 53-57 20647328-10 2010 Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin. Aspirin 182-189 cyclin dependent kinase 2 Homo sapiens 53-57 20682078-9 2010 Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IkappaB phosphorylation and blocked NF-kappaB nuclear import. lycorine 0-8 cyclin dependent kinase 2 Homo sapiens 84-88 20682067-6 2010 alpha-Santalol altered expressions of cell cycle proteins such as cyclin A, cyclin B1, Cdc2, Cdc25c, p-Cdc25c and Cdk2. a-santalol 0-14 cyclin dependent kinase 2 Homo sapiens 114-118 20803121-8 2010 Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Quercetin 0-9 cyclin dependent kinase 2 Homo sapiens 72-76 20587660-4 2010 Ascofuranone-induced p21(WAF1/CIP1) associates with CDK2 and prevents CDK2-cyclin E complex formation, leading to the inactivation of E2F transcriptional activity. ascofuranone 0-12 cyclin dependent kinase 2 Homo sapiens 52-56 21152226-5 2010 RESULTS: The expressions of CDK2 and cyclin D1 for different concentrations of DCA in normal colonocytes and colon cancer cells were similar, but the expressions of cyclin E and A were significantly different. Deoxycholic Acid 79-82 cyclin dependent kinase 2 Homo sapiens 28-32 21152226-9 2010 Our results suggest that a low dose of DCA induces cellular proliferation through increased expression of cyclin A and that a high dose of DCA induces decreased expression of cyclin E and CDK2 in normal colonocytes. Deoxycholic Acid 139-142 cyclin dependent kinase 2 Homo sapiens 188-192 20630104-12 2010 The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21Cip1 and p27Kip1 and the decrease of CDK2. Fluorouracil 45-49 cyclin dependent kinase 2 Homo sapiens 129-133 20630104-12 2010 The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21Cip1 and p27Kip1 and the decrease of CDK2. Chloroquine 53-55 cyclin dependent kinase 2 Homo sapiens 129-133 20473330-7 2010 These studies showed a highly specific role for Rb in mediating the response to CDK4/6 inhibition that was dependent on transcriptional repression manifest through E2F, and the ability to attenuate CDK2 activity. Rubidium 48-50 cyclin dependent kinase 2 Homo sapiens 198-202 20473330-8 2010 Acquired resistance to PD-03322991 was specifically associated with attenuation of CDK2 inhibitors, indicating that redundancy in CDK functions represents a determinant of therapeutic failure. pd-03322991 23-34 cyclin dependent kinase 2 Homo sapiens 83-87 20587660-4 2010 Ascofuranone-induced p21(WAF1/CIP1) associates with CDK2 and prevents CDK2-cyclin E complex formation, leading to the inactivation of E2F transcriptional activity. ascofuranone 0-12 cyclin dependent kinase 2 Homo sapiens 70-74 20368335-6 2010 C37 with alanine substitution for Thr-507 (C37/T507A) that imitated the cleavage product during staurosporine treatment interacted with Cdc2, Cdk2, cyclin A, and cyclin B1 and markedly activated cyclin B1/Cdc2. Staurosporine 96-109 cyclin dependent kinase 2 Homo sapiens 142-146 20479412-0 2010 Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 35-42 cyclin dependent kinase 2 Homo sapiens 67-71 20479412-1 2010 PURPOSE: SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) 2, 7, and 9, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 9-16 cyclin dependent kinase 2 Homo sapiens 89-93 20530684-5 2010 Specifically, the cyclin E/CDK2 complex phosphorylates Cdc25C on Ser(214), leading to its premature activation, which coincides with higher cyclin B/CDK1 and Polo-like kinase 1 (PLK1) activities in an S-phase-enriched population that result in faster mitotic entry. Serine 65-68 cyclin dependent kinase 2 Homo sapiens 27-31 20368335-7 2010 The dephosphorylation of Thr-507 might expose the Cdc2/Cdk2-docking site in C37. Threonine 25-28 cyclin dependent kinase 2 Homo sapiens 55-59 20466538-12 2010 Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. Threonine 81-84 cyclin dependent kinase 2 Homo sapiens 72-76 20466538-12 2010 Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. Threonine 81-84 cyclin dependent kinase 2 Homo sapiens 286-290 20466538-12 2010 Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. Serine 101-104 cyclin dependent kinase 2 Homo sapiens 72-76 20466538-12 2010 Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. Serine 101-104 cyclin dependent kinase 2 Homo sapiens 286-290 20422243-4 2010 In this analysis, the canonical cyclin binding motif PSTAIRE of CDK2 is replaced by a novel DARTLRE motif and Thr160 residue, phosphorylation of which is required for positive regulation of CDK2, is replaced by a tyrosine (Tyr174) in ( Ta ) 5B2. Tyrosine 213-221 cyclin dependent kinase 2 Homo sapiens 64-68 20385192-5 2010 Astaxanthin-induced activation of PI3K and its downstream mediators, p-MEK, p-ERK, and p-Stat3 in NSCs resulted in subsequent induction of expression of proliferation-related transcription factors (Rex1, CDK1, and CDK2) and stemness genes (OCT4, SOX2, Nanog, and KLF4). astaxanthine 0-11 cyclin dependent kinase 2 Homo sapiens 214-218 20448906-10 2010 N-Alkylation of the sulfonamide reduced CDK-2 inhibitory activity, while a substituted benzyl or 3-phenylpropyl group on the sulfonamide resulted in a loss of potency compared with 3-(6-cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide. Sulfonamides 20-31 cyclin dependent kinase 2 Homo sapiens 40-45 20361800-1 2010 To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3"-oxime derivatives with combined substitutions at the 5 and 5" positions. indirubin 26-35 cyclin dependent kinase 2 Homo sapiens 59-63 20361800-2 2010 A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5" position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Halogens 74-81 cyclin dependent kinase 2 Homo sapiens 142-146 20361800-2 2010 A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5" position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Halogens 74-81 cyclin dependent kinase 2 Homo sapiens 214-218 20361800-2 2010 A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5" position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Adenosine Triphosphate 122-125 cyclin dependent kinase 2 Homo sapiens 142-146 20361800-2 2010 A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5" position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Adenosine Triphosphate 122-125 cyclin dependent kinase 2 Homo sapiens 214-218 20361800-3 2010 Among the synthesized derivatives, the 5-nitro-5"-hydroxy analogue 3a and the 5-nitro-5"-fluoro analogue 5a displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. 5-nitro-5" 39-49 cyclin dependent kinase 2 Homo sapiens 153-157 20361800-3 2010 Among the synthesized derivatives, the 5-nitro-5"-hydroxy analogue 3a and the 5-nitro-5"-fluoro analogue 5a displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. hydroxide ion 50-57 cyclin dependent kinase 2 Homo sapiens 153-157 20361800-3 2010 Among the synthesized derivatives, the 5-nitro-5"-hydroxy analogue 3a and the 5-nitro-5"-fluoro analogue 5a displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. 5-nitro-5"-fluoro 78-95 cyclin dependent kinase 2 Homo sapiens 153-157 19941148-6 2010 RESULTS: The treatment with DHA resulted in a dose-dependent G(0)/G(1) cell cycle arrest and regulated the expression of some cyclins, cdks and cdk inhibitors that involved in the G(0)/G(1) cell cycle progression such as cyclin E, cdk2, cdk4 and p27(Kip1) in pancreatic cancer BxPC-3 and AsPC-1 cells. artenimol 28-31 cyclin dependent kinase 2 Homo sapiens 231-235 20448898-0 2010 Synthesis and biological evaluation of 5-substituted O4-alkylpyrimidines as CDK2 inhibitors. 5-substituted o4-alkylpyrimidines 39-72 cyclin dependent kinase 2 Homo sapiens 76-80 20448898-1 2010 CDK2 inhibitory structure-activity relationships have been explored for a range of 5-substituted O(4)-alkylpyrimidines. o(4)-alkylpyrimidines 97-118 cyclin dependent kinase 2 Homo sapiens 0-4 20448898-6 2010 Similarly, in the N(2)-arylsulfonamido-5-(hydroxyiminomethyl) series the O(4)-sec-butyl substituent conferred greater potency than the cyclohexylmethyl (23c, (rac)-4-(4-amino-6-sec-butoxy-5-(hydroxyiminomethyl)pyrimidin-2-ylamino)benzenesulfonamide; CDK2 IC(50) = 7.4 nM). n(2)-arylsulfonamido-5-(hydroxyiminomethyl) 18-61 cyclin dependent kinase 2 Homo sapiens 250-254 20448898-6 2010 Similarly, in the N(2)-arylsulfonamido-5-(hydroxyiminomethyl) series the O(4)-sec-butyl substituent conferred greater potency than the cyclohexylmethyl (23c, (rac)-4-(4-amino-6-sec-butoxy-5-(hydroxyiminomethyl)pyrimidin-2-ylamino)benzenesulfonamide; CDK2 IC(50) = 7.4 nM). 2-ethylhexanal 82-87 cyclin dependent kinase 2 Homo sapiens 250-254 20448898-6 2010 Similarly, in the N(2)-arylsulfonamido-5-(hydroxyiminomethyl) series the O(4)-sec-butyl substituent conferred greater potency than the cyclohexylmethyl (23c, (rac)-4-(4-amino-6-sec-butoxy-5-(hydroxyiminomethyl)pyrimidin-2-ylamino)benzenesulfonamide; CDK2 IC(50) = 7.4 nM). cyclohexylmethyl ( 135-153 cyclin dependent kinase 2 Homo sapiens 250-254 20448906-7 2010 3-(6-Cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide derivatives were assayed as inhibitors of human cyclin-dependent kinase 2. 3-(6-cyclohexylmethoxy-9h-purin-2-ylamino)phenylmethanesulfonamide 0-66 cyclin dependent kinase 2 Homo sapiens 115-140 20448906-8 2010 Previous structure-activity studies demonstrated that relocating the sulfonamide group of O(6)-cyclohexylmethoxy-2-(4"-sulfamoylanilino)purine from the 4- to the 3-position on the 2-arylamino ring resulted in a 40-fold reduction in potency against CDK2. Sulfonamides 69-80 cyclin dependent kinase 2 Homo sapiens 248-252 20448906-8 2010 Previous structure-activity studies demonstrated that relocating the sulfonamide group of O(6)-cyclohexylmethoxy-2-(4"-sulfamoylanilino)purine from the 4- to the 3-position on the 2-arylamino ring resulted in a 40-fold reduction in potency against CDK2. NU6102 90-142 cyclin dependent kinase 2 Homo sapiens 248-252 20646592-5 2010 And the expressions of cell cycle protein P53, P21, CDK2 were detected by Western blot after the treatment of capsaicin. Capsaicin 110-119 cyclin dependent kinase 2 Homo sapiens 52-56 20646592-11 2010 After a 48-hour treatment with capsaicin, the expressions of P53 and P21 were up-regulated in contrary to the expression of CDK2. Capsaicin 31-40 cyclin dependent kinase 2 Homo sapiens 124-128 20646592-12 2010 CONCLUSION: Capsaicin induces the cell cycle arrest of bladder cancer RT4 cells G(0)/G(1) phase and growth inhibition via TRPV1 receptor by modulating the expression of P53, P21 and CDK2. Capsaicin 12-21 cyclin dependent kinase 2 Homo sapiens 182-186 20422243-4 2010 In this analysis, the canonical cyclin binding motif PSTAIRE of CDK2 is replaced by a novel DARTLRE motif and Thr160 residue, phosphorylation of which is required for positive regulation of CDK2, is replaced by a tyrosine (Tyr174) in ( Ta ) 5B2. Tyrosine 213-221 cyclin dependent kinase 2 Homo sapiens 190-194 20183853-3 2010 Four kinase systems (Src family, Abl/c-Kit, Syk/ZAP-70, and CDK2/4) were investigated, and differences in predicted water molecule locations and energetics were able to explain the experimentally observed binding selectivity profiles. Water 116-121 cyclin dependent kinase 2 Homo sapiens 60-66 21188035-6 2010 Present study is focused on development, optimization and validation of cyclin-dependent kinase 2 assay which is suitable for identification potent and selective, ATP competitive and non-competitive inhibitors of cyclin-dependent kinase 2. Adenosine Triphosphate 163-166 cyclin dependent kinase 2 Homo sapiens 72-97 21188035-6 2010 Present study is focused on development, optimization and validation of cyclin-dependent kinase 2 assay which is suitable for identification potent and selective, ATP competitive and non-competitive inhibitors of cyclin-dependent kinase 2. Adenosine Triphosphate 163-166 cyclin dependent kinase 2 Homo sapiens 213-238 21188035-8 2010 Both cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E complexes, have different affinity for ATP. Adenosine Triphosphate 154-157 cyclin dependent kinase 2 Homo sapiens 5-30 21188035-8 2010 Both cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E complexes, have different affinity for ATP. Adenosine Triphosphate 154-157 cyclin dependent kinase 2 Homo sapiens 41-66 21188035-8 2010 Both cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E complexes, have different affinity for ATP. Adenosine Triphosphate 154-157 cyclin dependent kinase 2 Homo sapiens 41-66 20153225-0 2010 Why pyridine containing pyrido[2,3-d]pyrimidin-7-ones selectively inhibit CDK4 than CDK2: insights from molecular dynamics simulation. pyrido[2,3-d]pyrimidin-7-ones 24-53 cyclin dependent kinase 2 Homo sapiens 84-88 20198345-4 2010 In addition, inhibition of cyclin A/Cdk2 interfered with S-phase progression further in agreement with the result of bivariate flow cytometric analysis which indicated that DNA synthesis time (Ts) was significantly prolonged by DHA in MHCC97L. Dihydroalprenolol 228-231 cyclin dependent kinase 2 Homo sapiens 36-40 20153225-0 2010 Why pyridine containing pyrido[2,3-d]pyrimidin-7-ones selectively inhibit CDK4 than CDK2: insights from molecular dynamics simulation. pyridine 4-12 cyclin dependent kinase 2 Homo sapiens 84-88 20445224-6 2010 The ability of Myc to suppress senescence was dependent on phosphorylation of Myc at Ser 62 by cyclin-dependent kinase 2 (Cdk2), uncovering a new non-redundant role of this kinase. Serine 85-88 cyclin dependent kinase 2 Homo sapiens 95-120 20445224-6 2010 The ability of Myc to suppress senescence was dependent on phosphorylation of Myc at Ser 62 by cyclin-dependent kinase 2 (Cdk2), uncovering a new non-redundant role of this kinase. Serine 85-88 cyclin dependent kinase 2 Homo sapiens 122-126 19825886-1 2010 BACKGROUND: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. AZD5438 12-19 cyclin dependent kinase 2 Homo sapiens 68-72 19825886-1 2010 BACKGROUND: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. AZD5438 12-19 cyclin dependent kinase 2 Homo sapiens 83-87 19828235-4 2010 Induction of G1 arrest by widdrol was correlated with induction of Chk2, p53 phosphorylation and CDK inhibitor p21 expression as well as inhibition of cyclin E, cyclin-dependent kinase (CDK2) and retinoblastoma protein (pRB). widdrol 26-33 cyclin dependent kinase 2 Homo sapiens 186-190 20079829-6 2010 Expression of various cell cycle regulators such as Cdk2, cyclin B, and cyclin E was significantly augmented in cells treated with 10-50 microM DETA-NO. DETA-NO 144-151 cyclin dependent kinase 2 Homo sapiens 52-56 20334651-9 2010 We found that alsterpaullone effectively inhibits cdk2 activity in HIV-1 infected cells with a low IC50 compared to control uninfected cells. alsterpaullone 14-28 cyclin dependent kinase 2 Homo sapiens 50-54 20334651-10 2010 The effects of alsterpaullone were associated with suppression of cdk2 and cyclin expression. alsterpaullone 15-29 cyclin dependent kinase 2 Homo sapiens 66-70 20079829-7 2010 The proliferative effect of NO was blocked by roscovitine, a Cdk2 inhibitor. Roscovitine 46-57 cyclin dependent kinase 2 Homo sapiens 61-65 20079829-8 2010 S-nitrosylation of Cdk2 and an increase in the Cdk2-associated kinase activity was observed for the first time in DETA-NO-treated cells. DETA-NO 114-121 cyclin dependent kinase 2 Homo sapiens 19-23 20079829-8 2010 S-nitrosylation of Cdk2 and an increase in the Cdk2-associated kinase activity was observed for the first time in DETA-NO-treated cells. DETA-NO 114-121 cyclin dependent kinase 2 Homo sapiens 47-51 20079829-9 2010 This study demonstrates that the DETA-NO-mediated biphasic effect was dependent on Cdk2 nitrosylation/activation and the loss of mitochondrial potential at low and high concentrations, respectively. DETA-NO 33-40 cyclin dependent kinase 2 Homo sapiens 83-87 20146435-4 2010 The most potent compound reported in this study inhibits CDK2 with an IC(50) of 0.7 nM ([ATP] = 100 microM). Adenosine Triphosphate 89-92 cyclin dependent kinase 2 Homo sapiens 57-61 20146435-5 2010 Furthermore, an X-ray crystal structure of 2-methyl-N-(3-(nitro)phenyl)-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine (11g), a representative from the chemical series in complex with cyclin A-CDK2, is reported, confirming the design rationale and expected binding mode within the CDK2 ATP binding pocket. 2-methyl-n-(3-(nitro)phenyl)-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine 43-116 cyclin dependent kinase 2 Homo sapiens 191-195 20146435-5 2010 Furthermore, an X-ray crystal structure of 2-methyl-N-(3-(nitro)phenyl)-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine (11g), a representative from the chemical series in complex with cyclin A-CDK2, is reported, confirming the design rationale and expected binding mode within the CDK2 ATP binding pocket. 2-methyl-n-(3-(nitro)phenyl)-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine 43-116 cyclin dependent kinase 2 Homo sapiens 279-283 20186868-5 2010 Western blot analysis on DU145 cells treated with compounds 7 and 9 demonstrated that 7-azaisoindigo derivatives could decrease the level of CDK2 activity (phosphorylation) and the expression of cyclin D1, and increase the expression of endogenous cyclin-dependent inhibitor p27. 7-azaisoindigo 86-100 cyclin dependent kinase 2 Homo sapiens 141-145 20215421-7 2010 Consistent with these growth results, molecular analysis indicates that tamoxifen-resistant cells express higher levels of cyclin E1, cdk2, ACTR, and E2F1. Tamoxifen 72-81 cyclin dependent kinase 2 Homo sapiens 134-138 20147522-7 2010 Reduction in CDK2 activity by 1,25-(OH)(2)D(3) was associated with decreased T160 phosphorylation, a residue whose phosphorylation in the nucleus is essential for CDK2 activity. 2,2',2''-trichlorotriethylamine 77-81 cyclin dependent kinase 2 Homo sapiens 13-17 20147522-7 2010 Reduction in CDK2 activity by 1,25-(OH)(2)D(3) was associated with decreased T160 phosphorylation, a residue whose phosphorylation in the nucleus is essential for CDK2 activity. 2,2',2''-trichlorotriethylamine 77-81 cyclin dependent kinase 2 Homo sapiens 163-167 20147522-13 2010 These data establish central roles for CDK2 nuclear-cytoplasmic trafficking and cyclin E in the mechanism of 1,25-(OH)(2)D(3)-mediated growth inhibition in prostate cancer cells. 25-(oh) 111-118 cyclin dependent kinase 2 Homo sapiens 39-43 19908241-7 2010 In Western blot, combined TGZ and ASA also could downregulate Cdk2, E2F-1, cyclin B1, cyclin D3 protein, and the ratio of phospho-Rb/Rb. Troglitazone 26-29 cyclin dependent kinase 2 Homo sapiens 62-66 19908241-7 2010 In Western blot, combined TGZ and ASA also could downregulate Cdk2, E2F-1, cyclin B1, cyclin D3 protein, and the ratio of phospho-Rb/Rb. Aspirin 34-37 cyclin dependent kinase 2 Homo sapiens 62-66 19908243-4 2010 In mechanistic studies, silibinin (50-75 microM) modulated the protein levels of cyclin-dependent kinases (CDKs) (4, 6, and 2), cyclins (D1, D3, and E), CDKIs (p18/INK4C, p21/Cip1, and p27/Kip1) in a differential manner in these three cell lines. Silybin 24-33 cyclin dependent kinase 2 Homo sapiens 107-111 20147522-0 2010 Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Vitamin D 129-138 cyclin dependent kinase 2 Homo sapiens 21-46 20045222-0 2010 Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. pyrimidine 54-64 cyclin dependent kinase 2 Homo sapiens 80-84 20045222-1 2010 Novel derivatives of 2,4,5,6-tetrasubstituted pyrimidine cyclin-dependent kinase (CDK2) inhibitors was designed and synthesized. 2,4,5,6-tetrasubstituted 21-45 cyclin dependent kinase 2 Homo sapiens 82-86 20127023-5 2010 KBH-A42 mediated G0/G1 cell cycle arrest, probably as the result of the down-regulation of CDK2, CDK4 and CDK6 and the up-regulation of p21WAF1. KBH A42 0-7 cyclin dependent kinase 2 Homo sapiens 91-95 19895793-6 2010 Cell cycle regulatory gene analysis showed increased protein levels of cyclin A, cyclin B, Chk2, Cdk2, and P27 in hepatoma cells after time courses of emodin treatment, and Western blot analysis showed decreased protein levels of Cdc25c and P21. Emodin 151-157 cyclin dependent kinase 2 Homo sapiens 97-101 20145171-7 2010 Androstenedione-induced G(1) exit correlated with increased cyclin E-associated kinase activity and increased CDK2 levels. Androstenedione 0-15 cyclin dependent kinase 2 Homo sapiens 110-114 20097066-1 2010 Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. Aristolochic Acids 19-37 cyclin dependent kinase 2 Homo sapiens 127-131 20097066-3 2010 Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. Aristololactam 15-27 cyclin dependent kinase 2 Homo sapiens 85-89 20145171-8 2010 Letrozole treatment inhibited cyclin E-CDK2 kinase activity by preventing the androstenedione-induced increase in CDK2. Letrozole 0-9 cyclin dependent kinase 2 Homo sapiens 39-43 20145171-8 2010 Letrozole treatment inhibited cyclin E-CDK2 kinase activity by preventing the androstenedione-induced increase in CDK2. Letrozole 0-9 cyclin dependent kinase 2 Homo sapiens 114-118 20145171-8 2010 Letrozole treatment inhibited cyclin E-CDK2 kinase activity by preventing the androstenedione-induced increase in CDK2. Androstenedione 78-93 cyclin dependent kinase 2 Homo sapiens 39-43 20145171-8 2010 Letrozole treatment inhibited cyclin E-CDK2 kinase activity by preventing the androstenedione-induced increase in CDK2. Androstenedione 78-93 cyclin dependent kinase 2 Homo sapiens 114-118 20145171-10 2010 Roscovitine blocked the androstenedione-induced increase in CDK2, and LMW-E overexpression could not bypass this effect. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 60-64 20145171-10 2010 Roscovitine blocked the androstenedione-induced increase in CDK2, and LMW-E overexpression could not bypass this effect. Androstenedione 24-39 cyclin dependent kinase 2 Homo sapiens 60-64 19922488-8 2010 These findings strongly suggest that anti-proliferative effects of gamma-tocotrienol are associated with reduction in cell cycle progression from G(1) to S, as evidenced by increased p27 levels, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6 and phosphorylated Rb levels. plastochromanol 8 67-84 cyclin dependent kinase 2 Homo sapiens 238-242 20460749-7 2010 Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). Ouabain 121-128 cyclin dependent kinase 2 Homo sapiens 280-314 19585470-6 2010 When treated with the compound in T47D cells, schizandrin induced the accumulation of a cell population in the G0/G1 phase, which was further demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A, CDK2 and CDK4. schizandrin 46-57 cyclin dependent kinase 2 Homo sapiens 304-308 19747539-8 2010 Both SP600125 and PD98059 attenuated Bad up-regulation, and reversed down-regulation of Bcl-2, Bcl-X(L), survivin, cyclin A, cyclin B, and Cdk2 in NFD-treated cells. pyrazolanthrone 5-13 cyclin dependent kinase 2 Homo sapiens 139-143 19747539-8 2010 Both SP600125 and PD98059 attenuated Bad up-regulation, and reversed down-regulation of Bcl-2, Bcl-X(L), survivin, cyclin A, cyclin B, and Cdk2 in NFD-treated cells. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 18-25 cyclin dependent kinase 2 Homo sapiens 139-143 20010939-2 2010 Anti-estrogens, such as tamoxifen, antagonise estrogen-induced ERalpha transactivation of cyclin D1, resulting in reduced CDK4/6 activity, p27(Kip1)-mediated inhibition of CDK2 and growth arrest. Tamoxifen 24-33 cyclin dependent kinase 2 Homo sapiens 172-176 20010939-4 2010 METHODS: The cellular effects of CDK2/1 siRNA knockdown and purine-based CDK2/1 inhibitors, NU2058 and NU6102, were measured in anti-estrogen-sensitive and resistant breast cancer cell lines. purine 60-66 cyclin dependent kinase 2 Homo sapiens 73-77 20008003-7 2010 Cdk2/cyclin A also potentiated the partial agonist activity of RU486; however, phosphorylation of serine 400 was not required, indicating that JDP-2 and Cdk2/cyclin A act by distinct mechanisms. Mifepristone 63-68 cyclin dependent kinase 2 Homo sapiens 0-4 20008003-7 2010 Cdk2/cyclin A also potentiated the partial agonist activity of RU486; however, phosphorylation of serine 400 was not required, indicating that JDP-2 and Cdk2/cyclin A act by distinct mechanisms. Mifepristone 63-68 cyclin dependent kinase 2 Homo sapiens 153-157 20080565-4 2010 We report that GRK2 protein levels are transiently down-regulated during the G2/M transition by a mechanism involving CDK2-mediated phosphorylation of GRK2 at Serine670, which triggers binding to the prolyl-isomerase Pin1 and subsequent degradation. serine670 159-168 cyclin dependent kinase 2 Homo sapiens 118-122 20460749-7 2010 Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). Ouabain 0-7 cyclin dependent kinase 2 Homo sapiens 280-314 20460749-7 2010 Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). Ouabain 0-7 cyclin dependent kinase 2 Homo sapiens 316-320 20460749-7 2010 Ouabain could induce HepG2 cell apoptosis and generate S phase arrest, and siRNA could enhance the anti-cancer effect of ouabain that induced HepG2 cells apoptosis via an intracellular Ca(2+) and ROS increase-mediated, and generated cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/proliferating cell nuclear antigen (PCNA) complex product and increasing the expression of cyclin-dependent kinase inhibitor 1A (P21(CIP1)). Ouabain 121-128 cyclin dependent kinase 2 Homo sapiens 316-320 19797611-6 2010 In cells arrested in S phase by a thymidine block and then released into a synchronous cell cycle, there was a clear dissociation among the activation of CDK2 and the expression of UGT1A1, CYP2B6, and CYP3A4. Thymidine 34-43 cyclin dependent kinase 2 Homo sapiens 154-158 20686221-9 2010 Moreover, curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. Curcumin 10-18 cyclin dependent kinase 2 Homo sapiens 179-183 19879023-4 2010 Quinolin-4-yl-substituted compound, 8, presents cytotoxic activity and is most effective and selective against CDK1/CycA than against CDK2/CycB. quinolin-4-yl 0-13 cyclin dependent kinase 2 Homo sapiens 134-138 20030297-0 2010 Computational study of the interactions between guanine derivatives and cyclin-dependent kinase 2 (CDK2) by CoMFA and QM/MM. Guanine 48-55 cyclin dependent kinase 2 Homo sapiens 72-97 20030297-0 2010 Computational study of the interactions between guanine derivatives and cyclin-dependent kinase 2 (CDK2) by CoMFA and QM/MM. Guanine 48-55 cyclin dependent kinase 2 Homo sapiens 99-103 20030297-1 2010 Comparative molecular field analysis (CoMFA) and QM/MM hybrid calculations were performed on 9H-purine derivatives as CDK2 inhibitors. purine 93-102 cyclin dependent kinase 2 Homo sapiens 118-122 19956888-1 2010 Roscovitine, a cyclin-dependent kinases (CDKs) inhibitor, has been reported to have anti-tumor effects in some cancer cell lines by inducing apoptosis. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 41-45 19858290-2 2010 Inactivating human cyclin A/Cdk2 complexes through diverse approaches delays mitotic entry and promotes inhibitory phosphorylation of Cdk1 on tyrosine 15, a modification performed by Wee1. Tyrosine 142-150 cyclin dependent kinase 2 Homo sapiens 28-32 20010815-6 2010 Cdk2-/- MEFs also senesced upon ectopic Wnt signalling or, without an oncogene, upon oxygen-induced culture shock. Oxygen 85-91 cyclin dependent kinase 2 Homo sapiens 0-4 19956888-5 2010 CDK2 activity and PCNA expression were repressed with increasing dose of roscovitine. Roscovitine 73-84 cyclin dependent kinase 2 Homo sapiens 0-4 20067177-1 2009 The nanosecond-long molecular dynamics of the movement of the active protein kinase CDK2/ATP complex has been analyzed. Adenosine Triphosphate 89-92 cyclin dependent kinase 2 Homo sapiens 84-88 19812034-3 2009 Exposure of cells to mitomycin C or UV irradiation, but not ionizing radiation, induces stabilization of cyclin E. Stabilization of cyclin E reduces the activity of Cdk2-cyclin A, resulting in a slowing of S phase progression and arrest. Mitomycin 21-32 cyclin dependent kinase 2 Homo sapiens 165-169 19487074-2 2009 The treatment of cells with piceatannol for 24h resulted in an increase in the percentage of cells in G1 phase and dose-dependent decreases in [(3)H]thymidine incorporation, as well as in protein levels of cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 and CDK4. 3,3',4,5'-tetrahydroxystilbene 28-39 cyclin dependent kinase 2 Homo sapiens 256-261 19487074-4 2009 Piceatannol reduced CDK4 and CDK2 activity. 3,3',4,5'-tetrahydroxystilbene 0-11 cyclin dependent kinase 2 Homo sapiens 29-33 19686743-8 2009 In HCCP, however, SKP2 was not degraded because of down-regulation of the phosphatase CDC14B, CDK2-dependent serine phosphorylation (which inhibits interaction between CDH1 and SKP2), and HINT1 inactivation. Serine 109-115 cyclin dependent kinase 2 Homo sapiens 94-98 19773423-9 2009 Moreover, we also observed that PCAF acetylates cdk2 at lysine 33. Lysine 56-62 cyclin dependent kinase 2 Homo sapiens 48-52 19626680-9 2009 Our results suggest that lower HIV-1 transcription at 3% O(2) compared to 21% O(2) may be mediated by lower activity of CDK9/cyclin T1 and Sp1 at 3% O(2) and that additional host cell factors such as CDK2 and NF-kappaB might be major regulators of HIV-1 transcription at low O(2) concentrations. Oxygen 57-61 cyclin dependent kinase 2 Homo sapiens 200-204 19787257-8 2009 Treatment with lovastatin or celecoxib decreased the levels of cyclin D1, CDK2, pRb and E2F1, while the combination treatment showed more pronounced suppression. Lovastatin 15-25 cyclin dependent kinase 2 Homo sapiens 74-78 19787257-8 2009 Treatment with lovastatin or celecoxib decreased the levels of cyclin D1, CDK2, pRb and E2F1, while the combination treatment showed more pronounced suppression. Celecoxib 29-38 cyclin dependent kinase 2 Homo sapiens 74-78 19773423-10 2009 As this lysine is essential for the interaction with ATP, acetylation of this residue inhibits cdk2 activity. Lysine 8-14 cyclin dependent kinase 2 Homo sapiens 95-99 19773423-10 2009 As this lysine is essential for the interaction with ATP, acetylation of this residue inhibits cdk2 activity. Adenosine Triphosphate 53-56 cyclin dependent kinase 2 Homo sapiens 95-99 19703905-6 2009 We have demonstrated that cyclin A/cdk2 specifically associates with APC in late G2 phase and phosphorylates it at Ser-1360, located in the mutation cluster region of APC. Serine 115-118 cyclin dependent kinase 2 Homo sapiens 35-39 19620837-6 2009 We show that gefitinib reduces p-Akt levels, concomitant with elevation of p21 levels and suppression of cdk2/4 and cyclinE/D1 activities, which result in impaired cell cycle progression through G1 arrest only in parental PC-9 cells, in which it inhibits growth. Gefitinib 13-22 cyclin dependent kinase 2 Homo sapiens 105-111 19631369-6 2009 However, the nuclear expression of CDK2 in epithelial cells was slightly elevated in PCOSE and significantly increased in HPCOSE when compared to NE. hpcose 122-128 cyclin dependent kinase 2 Homo sapiens 35-39 19789217-3 2009 Molecular analysis of tumors from animals treated sequentially with doxorubicin followed by zoledronic acid showed reduced numbers of proliferating tumor cells and decreased expression of cyclins E1, B, D1, and D3 as well as cdk2 and cdk4. Doxorubicin 68-79 cyclin dependent kinase 2 Homo sapiens 225-229 19789217-3 2009 Molecular analysis of tumors from animals treated sequentially with doxorubicin followed by zoledronic acid showed reduced numbers of proliferating tumor cells and decreased expression of cyclins E1, B, D1, and D3 as well as cdk2 and cdk4. Zoledronic Acid 92-107 cyclin dependent kinase 2 Homo sapiens 225-229 19346066-4 2009 Pentobarbital also leads to a G1 phase cell cycle arrest accompanied by suppressed G1 cell cycle regulatory proteins Cyclin D1, Cyclin D3, CDK2 and phosphorylated Rb. Pentobarbital 0-13 cyclin dependent kinase 2 Homo sapiens 139-143 19478553-4 2009 Treatment of synchronized leukemia cells with varying concentrations of SP600125 results in significant G2/M cell cycle arrest with elevated p21 levels, phosphorylation of histone H3 within 24 h, and endoreduplication with elevated Cdk2 protein levels after 48 h. SP600125 also induces significant abnormal microtubule dynamics in vivo. pyrazolanthrone 72-80 cyclin dependent kinase 2 Homo sapiens 232-236 19497615-1 2009 The aim of this study was to investigate whether roscovitine (the cyclin-dependent kinase 2 inhibitor) effectively induces synchronization of the donor cell cycle at G0/G1 and to examine the effect of donor cell cycle synchronization protocols on canine somatic cell nucleus transfer. Roscovitine 49-60 cyclin dependent kinase 2 Homo sapiens 66-91 19561638-2 2009 Previous studies have shown that the human NPM"s phosphorylation by cyclin E-cyclin-dependent kinase 2 (cdk2) on threonine (Thr) 199 regulates its translocation from the centrosome during cell cycle progression. Threonine 113-122 cyclin dependent kinase 2 Homo sapiens 75-102 19561638-2 2009 Previous studies have shown that the human NPM"s phosphorylation by cyclin E-cyclin-dependent kinase 2 (cdk2) on threonine (Thr) 199 regulates its translocation from the centrosome during cell cycle progression. Threonine 113-122 cyclin dependent kinase 2 Homo sapiens 104-108 19561638-2 2009 Previous studies have shown that the human NPM"s phosphorylation by cyclin E-cyclin-dependent kinase 2 (cdk2) on threonine (Thr) 199 regulates its translocation from the centrosome during cell cycle progression. Threonine 124-127 cyclin dependent kinase 2 Homo sapiens 75-102 19561638-2 2009 Previous studies have shown that the human NPM"s phosphorylation by cyclin E-cyclin-dependent kinase 2 (cdk2) on threonine (Thr) 199 regulates its translocation from the centrosome during cell cycle progression. Threonine 124-127 cyclin dependent kinase 2 Homo sapiens 104-108 19169685-0 2009 SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 0-7 cyclin dependent kinase 2 Homo sapiens 34-39 19169685-1 2009 PURPOSE: SNS-032 (formerly BMS-387032) is a potent, selective inhibitor of cyclin-dependent kinases (CDK) 2, 7 and 9, currently in phase 1 clinical trial for chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 9-16 cyclin dependent kinase 2 Homo sapiens 101-104 19169685-5 2009 RESULTS: SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 9-16 cyclin dependent kinase 2 Homo sapiens 57-61 19614620-2 2009 In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide 202-206 cyclin dependent kinase 2 Homo sapiens 84-88 19384950-6 2009 Additionally, we found that diosgenin caused G1 cell cycle arrest by downregulating cyclin D1, cdk-2 and cdk-4 expression in both ER(+) and ER(-) BCa cells resulting in the inhibition of cell proliferation and induction of apoptosis. Diosgenin 28-37 cyclin dependent kinase 2 Homo sapiens 95-100 19645506-4 2009 The CDK2-p21/Cip1 complex was increased, and the CDK2 kinase activity was decreased in the magnolol-treated U373. magnolol 91-99 cyclin dependent kinase 2 Homo sapiens 4-8 19645506-4 2009 The CDK2-p21/Cip1 complex was increased, and the CDK2 kinase activity was decreased in the magnolol-treated U373. magnolol 91-99 cyclin dependent kinase 2 Homo sapiens 49-53 19723061-0 2009 Is olomoucine, a weak CDK2 inhibitor, able to induce apoptosis in cancer cells? olomoucine 3-13 cyclin dependent kinase 2 Homo sapiens 22-26 19614620-2 2009 In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide 202-206 cyclin dependent kinase 2 Homo sapiens 90-115 19614620-2 2009 In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. pyrene dihydrodiol epoxide 216-242 cyclin dependent kinase 2 Homo sapiens 84-88 19614620-2 2009 In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. pyrene dihydrodiol epoxide 216-242 cyclin dependent kinase 2 Homo sapiens 90-115 19478079-3 2009 Phosphorylation on Thr(188) by MAPK or cyclin A/cdk2 primes the phosphorylations on Ser(184)/Thr(179) by GSK3beta, and these phosphorylations are required for the acquisition of DNA binding activity of C/EBPbeta. Threonine 19-22 cyclin dependent kinase 2 Homo sapiens 48-52 19478079-3 2009 Phosphorylation on Thr(188) by MAPK or cyclin A/cdk2 primes the phosphorylations on Ser(184)/Thr(179) by GSK3beta, and these phosphorylations are required for the acquisition of DNA binding activity of C/EBPbeta. Serine 84-87 cyclin dependent kinase 2 Homo sapiens 48-52 19478079-3 2009 Phosphorylation on Thr(188) by MAPK or cyclin A/cdk2 primes the phosphorylations on Ser(184)/Thr(179) by GSK3beta, and these phosphorylations are required for the acquisition of DNA binding activity of C/EBPbeta. Threonine 93-96 cyclin dependent kinase 2 Homo sapiens 48-52 19233286-6 2009 After heterodimer formation, Cyclin-A2 was phosphorylated only on Ser(14), whereas CDK2 contained two phosphorylated residues (Thr(39) and Thr(160)). Threonine 127-130 cyclin dependent kinase 2 Homo sapiens 83-87 19410453-2 2009 A preliminary screen of these compounds as phosphate donors with a typical wild type protein kinase (cdk2) and one of its known substrates p27(kip1) is also presented. Phosphates 43-52 cyclin dependent kinase 2 Homo sapiens 101-105 19423708-3 2009 We also show that mutation of the Ser(516) and Ser(645) residues causes a prolonged S phase checkpoint recovery after treatment with UV or aphidicolin, and that this delayed recovery process coincides with a prolonged stabilization of cyclin E and down-regulation of Cdk2 kinase activity. Serine 34-37 cyclin dependent kinase 2 Homo sapiens 267-271 19423708-3 2009 We also show that mutation of the Ser(516) and Ser(645) residues causes a prolonged S phase checkpoint recovery after treatment with UV or aphidicolin, and that this delayed recovery process coincides with a prolonged stabilization of cyclin E and down-regulation of Cdk2 kinase activity. Serine 47-50 cyclin dependent kinase 2 Homo sapiens 267-271 19535344-5 2009 Consistent with flavopiridol activity, phosphorylation at cdk2, cdk4, cdk9 sites on RB and RNA polymerase II was inhibited. alvocidib 16-28 cyclin dependent kinase 2 Homo sapiens 58-62 19233286-5 2009 The analysis of the monomeric proteins showed that Cyclin-A2 was phosphorylated on two Ser residues (Ser(14) and Ser(421)) and CDK2 on a single residue (Thr(160)). Threonine 153-156 cyclin dependent kinase 2 Homo sapiens 127-131 19472269-1 2009 Peptides that inhibit cyclin-dependent kinase 2 by blocking the macromolecular substrate recruitment site of cyclin A were simplified, for example, by replacement of dipeptide units with beta-amino acids. Dipeptides 166-175 cyclin dependent kinase 2 Homo sapiens 22-47 19472269-1 2009 Peptides that inhibit cyclin-dependent kinase 2 by blocking the macromolecular substrate recruitment site of cyclin A were simplified, for example, by replacement of dipeptide units with beta-amino acids. beta-amino acids 187-203 cyclin dependent kinase 2 Homo sapiens 22-47 19233286-6 2009 After heterodimer formation, Cyclin-A2 was phosphorylated only on Ser(14), whereas CDK2 contained two phosphorylated residues (Thr(39) and Thr(160)). Threonine 139-142 cyclin dependent kinase 2 Homo sapiens 83-87 19320493-7 2009 Significantly, the pep9 aptamers were able to detect subtle changes in the conformation of CDK2 associated with activation of its catalytic activity that may be caused by the phosphorylation of a single amino acid (threonine 160). Threonine 215-224 cyclin dependent kinase 2 Homo sapiens 91-95 19448431-3 2009 Here we report that pharmacologic inhibition of cdk2 with (R)-roscovitine blocked expansion of alloreactive T cells in vitro and in vivo and protected from lethal acute GvHD. Roscovitine 58-73 cyclin dependent kinase 2 Homo sapiens 48-52 19321444-2 2009 Coexpression of cyclin E results in further accumulation of CDC6 onto chromatin concomitantly with phosphorylation of CDK2 on Thr-160 and CDC6 on Ser-54. Threonine 126-129 cyclin dependent kinase 2 Homo sapiens 118-122 19135778-5 2009 The honokiol-induced cell cycle arrest was well correlated with the suppressive expression of CDK4, cyclin D1, CDK2, cyclin E, c-Myc, and phosphorylated retinoblastoma protein (pRb) at Ser780. honokiol 4-12 cyclin dependent kinase 2 Homo sapiens 111-115 19234140-2 2009 Here we studied the novel Cdk inhibitor SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 40-47 cyclin dependent kinase 2 Homo sapiens 113-117 19359655-10 2009 These findings demonstrate that combination low dose statin and gamma-tocotrienol treatment induced mammary tumor cell cycle arrest at G1, resulting from an increase in p27 expression, and a corresponding decrease in cyclin D1, CDK2, and hypophosphorylation of Rb protein. plastochromanol 8 64-81 cyclin dependent kinase 2 Homo sapiens 228-232 19472189-2 2009 It could specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes, including of several oncogenes (e.g., N-Myc, CrkL, Wnt10b, RIZ, and hTERT) and genes involved in the control of cell cycle (e.g., Cyclin G1 and CDK2) and signal transduction (e.g., STAT1, MAP3K11, and PIK3CB). Lysine 46-52 cyclin dependent kinase 2 Homo sapiens 260-264 19426695-0 2009 The kinase inhibitor O6-cyclohexylmethylguanine (NU2058) potentiates the cytotoxicity of cisplatin by mechanisms that are independent of its effect upon CDK2. NU2058 49-55 cyclin dependent kinase 2 Homo sapiens 153-157 19426695-1 2009 O(6)-Cyclohexylmethylguanine (NU2058) was developed as an inhibitor of CDK2 and was previously shown to potentiate cisplatin cytotoxicity in vitro. (6)-cyclohexylmethylguanine 1-28 cyclin dependent kinase 2 Homo sapiens 71-75 19426695-1 2009 O(6)-Cyclohexylmethylguanine (NU2058) was developed as an inhibitor of CDK2 and was previously shown to potentiate cisplatin cytotoxicity in vitro. NU2058 30-36 cyclin dependent kinase 2 Homo sapiens 71-75 19426695-8 2009 NU6230 (CDK2 IC(50) 18 microM) was equipotent to NU2058 (CDK2 IC(50) 17 microM) as a CDK2 inhibitor in cell-free and cell-based assays, yet did not potentiate cisplatin cytotoxicity. nu6230 0-6 cyclin dependent kinase 2 Homo sapiens 8-12 19426695-9 2009 Furthermore, NU6102 was >1000-fold more potent than NU2058 as a CDK2 inhibitor (CDK2 IC(50) 5 nM) yet was no more active than NU2058 in potentiating cisplatin. NU6102 13-19 cyclin dependent kinase 2 Homo sapiens 67-71 19426695-9 2009 Furthermore, NU6102 was >1000-fold more potent than NU2058 as a CDK2 inhibitor (CDK2 IC(50) 5 nM) yet was no more active than NU2058 in potentiating cisplatin. NU6102 13-19 cyclin dependent kinase 2 Homo sapiens 83-87 19426695-9 2009 Furthermore, NU6102 was >1000-fold more potent than NU2058 as a CDK2 inhibitor (CDK2 IC(50) 5 nM) yet was no more active than NU2058 in potentiating cisplatin. NU2058 55-61 cyclin dependent kinase 2 Homo sapiens 67-71 19426695-9 2009 Furthermore, NU6102 was >1000-fold more potent than NU2058 as a CDK2 inhibitor (CDK2 IC(50) 5 nM) yet was no more active than NU2058 in potentiating cisplatin. NU2058 55-61 cyclin dependent kinase 2 Homo sapiens 83-87 19383849-3 2009 DHE suppresses the expression of cyclin D, cyclin A, cyclin-dependent kinase 2, and cdc25A and increases the amount of p53 and p21, resulting in G(0)/G(1)-S phase arrest in MCF-7 cells. dehydrocostus lactone 0-3 cyclin dependent kinase 2 Homo sapiens 53-78 19383849-6 2009 Reduction of SOCS-1 and SOCS-3 expression by small interfering RNA inhibits DHE-mediated signal transducer and activator of transcription-3 inhibition, p21 up-regulation, and cyclin-dependent kinase 2 blockade, supporting the hypothesis that DHE inhibits cell cycle progression and cell death through SOCS-1 and SOCS-3. dehydrocostus lactone 76-79 cyclin dependent kinase 2 Homo sapiens 175-200 19323453-1 2009 N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. Guanine 22-29 cyclin dependent kinase 2 Homo sapiens 81-85 19317452-1 2009 The series of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-dione and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-dione derivatives reported here represents a novel class of potential antitumor agents, which potently and selectively inhibit CDK4 over CDK2 and CDK1. 4-(benzylaminomethylene)isoquinoline-1,3-(2h,4h)-dione 14-68 cyclin dependent kinase 2 Homo sapiens 268-272 19317452-1 2009 The series of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-dione and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-dione derivatives reported here represents a novel class of potential antitumor agents, which potently and selectively inhibit CDK4 over CDK2 and CDK1. 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2h,4h)-dione 73-136 cyclin dependent kinase 2 Homo sapiens 268-272 19428934-6 2009 We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27(kip1) and decreased those of cyclin D2 and p-cdk2 in hOBs. Indomethacin 22-34 cyclin dependent kinase 2 Homo sapiens 159-163 19428934-6 2009 We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27(kip1) and decreased those of cyclin D2 and p-cdk2 in hOBs. Celecoxib 36-45 cyclin dependent kinase 2 Homo sapiens 159-163 19428934-6 2009 We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27(kip1) and decreased those of cyclin D2 and p-cdk2 in hOBs. Dexamethasone 50-63 cyclin dependent kinase 2 Homo sapiens 159-163 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. Nitrogen 38-40 cyclin dependent kinase 2 Homo sapiens 83-108 19239702-0 2009 Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells. Paclitaxel 14-24 cyclin dependent kinase 2 Homo sapiens 49-53 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. Nitrogen 38-40 cyclin dependent kinase 2 Homo sapiens 110-114 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. 6-Oxamyristic acid 45-47 cyclin dependent kinase 2 Homo sapiens 83-108 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. 6-Oxamyristic acid 45-47 cyclin dependent kinase 2 Homo sapiens 110-114 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. Guanine 60-67 cyclin dependent kinase 2 Homo sapiens 83-108 19323453-0 2009 Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations. Guanine 60-67 cyclin dependent kinase 2 Homo sapiens 110-114 19323453-1 2009 N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. Nitrogen 0-2 cyclin dependent kinase 2 Homo sapiens 81-85 19323453-1 2009 N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. 6-Oxamyristic acid 7-9 cyclin dependent kinase 2 Homo sapiens 81-85 19101503-5 2009 Binding of Ca(2+) or Zn(2+) ions to the doubly phosphorylated CDK2 peptide did not cause any change in absorbance, but increased the affinity of the peptide for Fe(3+) ions. Zinc 21-23 cyclin dependent kinase 2 Homo sapiens 62-66 19101503-6 2009 These results demonstrate that double phosphorylation of CDK2 peptides increases the stoichiometry of metal ion binding, and hence may contribute to the previously observed regulation of CDK2 activity by metal ions. Metals 102-107 cyclin dependent kinase 2 Homo sapiens 57-61 19101503-6 2009 These results demonstrate that double phosphorylation of CDK2 peptides increases the stoichiometry of metal ion binding, and hence may contribute to the previously observed regulation of CDK2 activity by metal ions. Metals 102-107 cyclin dependent kinase 2 Homo sapiens 187-191 19101503-6 2009 These results demonstrate that double phosphorylation of CDK2 peptides increases the stoichiometry of metal ion binding, and hence may contribute to the previously observed regulation of CDK2 activity by metal ions. Metals 204-209 cyclin dependent kinase 2 Homo sapiens 57-61 19101503-6 2009 These results demonstrate that double phosphorylation of CDK2 peptides increases the stoichiometry of metal ion binding, and hence may contribute to the previously observed regulation of CDK2 activity by metal ions. Metals 204-209 cyclin dependent kinase 2 Homo sapiens 187-191 19017637-2 2009 We have observed that artemisinin treatment triggers a stringent G1 cell cycle arrest of LNCaP (lymph node carcinoma of the prostate) human prostate cancer cells that is accompanied by a rapid down-regulation of CDK2 and CDK4 protein and transcript levels. artemisinin 22-33 cyclin dependent kinase 2 Homo sapiens 212-216 19017637-3 2009 Transient transfection with promoter-linked luciferase reporter plasmids revealed that artemisinin strongly inhibits CDK2 and CDK4 promoter activity. artemisinin 87-98 cyclin dependent kinase 2 Homo sapiens 117-121 19150984-5 2009 It can be phosphorylated by cyclin E/Cdk2 at 3 phosphorylation sites (Ser(1791), Ser(1794), and Ser(2150)). Serine 70-73 cyclin dependent kinase 2 Homo sapiens 37-41 19150984-5 2009 It can be phosphorylated by cyclin E/Cdk2 at 3 phosphorylation sites (Ser(1791), Ser(1794), and Ser(2150)). Serine 81-84 cyclin dependent kinase 2 Homo sapiens 37-41 19150984-5 2009 It can be phosphorylated by cyclin E/Cdk2 at 3 phosphorylation sites (Ser(1791), Ser(1794), and Ser(2150)). Serine 81-84 cyclin dependent kinase 2 Homo sapiens 37-41 19059218-5 2009 Inhibition of CHK1 kinase by Go6976, an inhibitor of CHK1 activity, can promote DNA damage and lead to the activation of CHK2, converting G2/M checkpoint into intra-S-phase checkpoint in which two parallel branches, the ATM-CHK2-CDC25A-CDK2 and the ATM-NBS1/SMC1 cascades, are involved. Go 6976 29-35 cyclin dependent kinase 2 Homo sapiens 236-240 19221488-5 2009 We propose that the S-phase NAD(+)/NADH redox status constitutes a redox signaling, which along with the cyclin E/cdk2 signaling regulates histone expression and S-phase progression. NAD 28-34 cyclin dependent kinase 2 Homo sapiens 114-118 19221488-5 2009 We propose that the S-phase NAD(+)/NADH redox status constitutes a redox signaling, which along with the cyclin E/cdk2 signaling regulates histone expression and S-phase progression. NAD 35-39 cyclin dependent kinase 2 Homo sapiens 114-118 19201832-4 2009 Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr(8) (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Threonine 88-91 cyclin dependent kinase 2 Homo sapiens 40-44 19097791-2 2009 A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). 2-(6-phenyl-1h indazol-3-yl)-1h-benzo[d]imidazoles 12-62 cyclin dependent kinase 2 Homo sapiens 94-99 19147767-6 2009 Decreased levels of cyclin-dependent kinases 2, 4, and 6, CDC2, and cyclins D1, D3, E, and A were observed, indicating an inhibitory effect of silibinin on cell cycle progression. Silybin 143-152 cyclin dependent kinase 2 Homo sapiens 20-56 19239702-4 2009 We hypothesized that cyclin-dependent kinase (CDK) 1 activity and CDK2 activity in cancer cells, which reflect the activation state of the spindle assembly checkpoint and the growth state, respectively, predict sensitivity to paclitaxel. Paclitaxel 226-236 cyclin dependent kinase 2 Homo sapiens 66-70 19239702-10 2009 Baseline CDK2 specific activity was higher in tumors that were sensitive to paclitaxel than in tumors that were resistant to paclitaxel. Paclitaxel 76-86 cyclin dependent kinase 2 Homo sapiens 9-13 19239702-10 2009 Baseline CDK2 specific activity was higher in tumors that were sensitive to paclitaxel than in tumors that were resistant to paclitaxel. Paclitaxel 125-135 cyclin dependent kinase 2 Homo sapiens 9-13 19239702-11 2009 CONCLUSIONS: The change in CDK1 specific activity of xenograft tumors after paclitaxel treatment and the CDK2 specific activity before paclitaxel treatment are both associated with the drug sensitivity in vivo. Paclitaxel 135-145 cyclin dependent kinase 2 Homo sapiens 105-109 18615713-3 2009 Most cdk2 inhibitors in clinical development target almost exclusively the catalytic ATP-binding pocket of cdk2. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 5-9 18615713-3 2009 Most cdk2 inhibitors in clinical development target almost exclusively the catalytic ATP-binding pocket of cdk2. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 107-111 18222060-3 2008 Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4 kinase activities with no change in their expression. esculetin 29-38 cyclin dependent kinase 2 Homo sapiens 76-80 18798266-6 2008 Treatment with OSU03012 also markedly reduced the levels of cyclin A and Cdk2 in TE/E7 and TE/V, but not in TE/E6 cell lines, which had significantly enhanced basal levels of cyclin A and Cdk2. OSU 03012 15-23 cyclin dependent kinase 2 Homo sapiens 73-77 18798266-6 2008 Treatment with OSU03012 also markedly reduced the levels of cyclin A and Cdk2 in TE/E7 and TE/V, but not in TE/E6 cell lines, which had significantly enhanced basal levels of cyclin A and Cdk2. OSU 03012 15-23 cyclin dependent kinase 2 Homo sapiens 188-192 18761330-3 2008 Recently synthesized CKIs, e.g., purine derivatives such as olomoucine (OLO) and roscovitine (ROSC) are non-genotoxic and exhibit increased selectivity towards CDK2 and CDK7/9. purine 33-39 cyclin dependent kinase 2 Homo sapiens 160-164 18761330-3 2008 Recently synthesized CKIs, e.g., purine derivatives such as olomoucine (OLO) and roscovitine (ROSC) are non-genotoxic and exhibit increased selectivity towards CDK2 and CDK7/9. olomoucine 60-70 cyclin dependent kinase 2 Homo sapiens 160-164 18761330-3 2008 Recently synthesized CKIs, e.g., purine derivatives such as olomoucine (OLO) and roscovitine (ROSC) are non-genotoxic and exhibit increased selectivity towards CDK2 and CDK7/9. olomoucine 72-75 cyclin dependent kinase 2 Homo sapiens 160-164 18761330-3 2008 Recently synthesized CKIs, e.g., purine derivatives such as olomoucine (OLO) and roscovitine (ROSC) are non-genotoxic and exhibit increased selectivity towards CDK2 and CDK7/9. Roscovitine 81-92 cyclin dependent kinase 2 Homo sapiens 160-164 18761330-3 2008 Recently synthesized CKIs, e.g., purine derivatives such as olomoucine (OLO) and roscovitine (ROSC) are non-genotoxic and exhibit increased selectivity towards CDK2 and CDK7/9. Roscovitine 94-98 cyclin dependent kinase 2 Homo sapiens 160-164 18761330-14 2008 Thus, the biological action of substituted purines is not restricted to the inhibition of CDKs and open new perspectives for their therapeutic applications. Purines 43-50 cyclin dependent kinase 2 Homo sapiens 90-94 18798257-4 2008 In the premalignant and malignant cell lines, OSU03012-induced growth inhibition, S-phase arrest, and apoptosis were accompanied by a marked increase in the activity of Erk1/2 and Cdk2/cyclin A. OSU 03012 46-54 cyclin dependent kinase 2 Homo sapiens 180-184 18761329-3 2008 In this study we raised the question whether roscovitine (ROSC), an inhibitor of cyclin-dependent kinases (CDKs) with increased selectivity towards CDK2, could be able to affect human leukemia HL-60 cells in which the p53 gene is inactivated and whether ROSC-induced effects could be additionally modulated by compounds of natural origin, especially by polyphenols e.g. RES. Roscovitine 45-56 cyclin dependent kinase 2 Homo sapiens 107-111 18761329-3 2008 In this study we raised the question whether roscovitine (ROSC), an inhibitor of cyclin-dependent kinases (CDKs) with increased selectivity towards CDK2, could be able to affect human leukemia HL-60 cells in which the p53 gene is inactivated and whether ROSC-induced effects could be additionally modulated by compounds of natural origin, especially by polyphenols e.g. RES. Roscovitine 45-56 cyclin dependent kinase 2 Homo sapiens 148-152 18761329-3 2008 In this study we raised the question whether roscovitine (ROSC), an inhibitor of cyclin-dependent kinases (CDKs) with increased selectivity towards CDK2, could be able to affect human leukemia HL-60 cells in which the p53 gene is inactivated and whether ROSC-induced effects could be additionally modulated by compounds of natural origin, especially by polyphenols e.g. RES. Roscovitine 58-62 cyclin dependent kinase 2 Homo sapiens 107-111 18761329-3 2008 In this study we raised the question whether roscovitine (ROSC), an inhibitor of cyclin-dependent kinases (CDKs) with increased selectivity towards CDK2, could be able to affect human leukemia HL-60 cells in which the p53 gene is inactivated and whether ROSC-induced effects could be additionally modulated by compounds of natural origin, especially by polyphenols e.g. RES. Roscovitine 58-62 cyclin dependent kinase 2 Homo sapiens 148-152 18222060-3 2008 Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4 kinase activities with no change in their expression. esculetin 29-38 cyclin dependent kinase 2 Homo sapiens 138-142 18784074-5 2008 Here we report that inhibition of cyclin-dependent kinases (Cdks) by kenpaullone and roscovitine (two small molecule inhibitors of Cdks that we identified in a screen for compounds that activate hPXR) leads to activation of hPXR-mediated CYP3A4 gene expression in HepG2 human liver carcinoma cells. Roscovitine 85-96 cyclin dependent kinase 2 Homo sapiens 60-64 18663430-8 2008 Mana-Hox induced mitotic arrest of the cell cycle identified by downregulation of cyclin E, cyclin A, and cyclin-dependent kinase 2 (Cdk2) and an increase of MPM-2 expression. hydrogen oxalate 5-8 cyclin dependent kinase 2 Homo sapiens 106-131 18663430-8 2008 Mana-Hox induced mitotic arrest of the cell cycle identified by downregulation of cyclin E, cyclin A, and cyclin-dependent kinase 2 (Cdk2) and an increase of MPM-2 expression. hydrogen oxalate 5-8 cyclin dependent kinase 2 Homo sapiens 133-137 18649995-6 2008 Immunoprecipitation showed that the formation of the CDK2-p21 complex, but not the CDK2-p27, CDK4-p21, and CDK4-p27 complex, was increased in the DPTH-N10-treated HUVEC. 5,5-diphenyl-2-thiohydantoin-N10 146-154 cyclin dependent kinase 2 Homo sapiens 53-57 18649995-7 2008 Kinase assay further demonstrated that CDK2, but not CDK4, kinase activity was decreased in the DPTH-N10-treated HUVEC. 5,5-diphenyl-2-thiohydantoin-N10 96-104 cyclin dependent kinase 2 Homo sapiens 39-43 18784074-5 2008 Here we report that inhibition of cyclin-dependent kinases (Cdks) by kenpaullone and roscovitine (two small molecule inhibitors of Cdks that we identified in a screen for compounds that activate hPXR) leads to activation of hPXR-mediated CYP3A4 gene expression in HepG2 human liver carcinoma cells. kenpaullone 69-80 cyclin dependent kinase 2 Homo sapiens 60-64 18784074-5 2008 Here we report that inhibition of cyclin-dependent kinases (Cdks) by kenpaullone and roscovitine (two small molecule inhibitors of Cdks that we identified in a screen for compounds that activate hPXR) leads to activation of hPXR-mediated CYP3A4 gene expression in HepG2 human liver carcinoma cells. kenpaullone 69-80 cyclin dependent kinase 2 Homo sapiens 131-135 18649995-9 2008 Taken together, these data suggest that DPTH-N10 inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally interrupts the cell cycle. 5,5-diphenyl-2-thiohydantoin-N10 40-48 cyclin dependent kinase 2 Homo sapiens 141-145 18784074-5 2008 Here we report that inhibition of cyclin-dependent kinases (Cdks) by kenpaullone and roscovitine (two small molecule inhibitors of Cdks that we identified in a screen for compounds that activate hPXR) leads to activation of hPXR-mediated CYP3A4 gene expression in HepG2 human liver carcinoma cells. Roscovitine 85-96 cyclin dependent kinase 2 Homo sapiens 131-135 19189664-5 2008 Berberine much greatly decreased G0/G1 phase-associated cyclin and cyclin-dependent kinase (cyclin D1, cyclin E, Cdk2, and Cdk4) expression, and increased apoptotic gene expression and activation of caspase-3 in SK-N-SH cells. Berberine 0-9 cyclin dependent kinase 2 Homo sapiens 113-117 18850315-4 2008 The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased in the progesterone-treated HUVEC. Progesterone 97-109 cyclin dependent kinase 2 Homo sapiens 17-21 18850315-4 2008 The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased in the progesterone-treated HUVEC. Progesterone 97-109 cyclin dependent kinase 2 Homo sapiens 30-34 18850315-4 2008 The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased in the progesterone-treated HUVEC. Progesterone 97-109 cyclin dependent kinase 2 Homo sapiens 30-34 18554781-6 2008 When analyzing the expression of cell cycle-related proteins, we found that HS-1200 reduced the expression levels of cyclin D1, cyclin A, and Cdk2. HS 1200 76-83 cyclin dependent kinase 2 Homo sapiens 142-146 19138991-3 2008 In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G(1) arrest. flavokawain A 77-90 cyclin dependent kinase 2 Homo sapiens 156-181 19138991-3 2008 In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G(1) arrest. flavokawain A 77-90 cyclin dependent kinase 2 Homo sapiens 183-187 18729080-9 2008 Finally, helenalin increased protein-protein interactions between p21 and cyclin-dependent kinase 2 (Cdk2) which may account in part for the anti-proliferative effect in 3T3-L1 preadipocytes. helenalin 9-18 cyclin dependent kinase 2 Homo sapiens 74-99 18539384-3 2008 In addition, LMP1 abolished the potentials of retinoic acid (RA) to down-regulate Cdk2 and Cdk4 and to up-regulate p16, p21, and p27, resulting in activation of E2F1 in the presence of RA. Tretinoin 46-59 cyclin dependent kinase 2 Homo sapiens 82-86 18539384-3 2008 In addition, LMP1 abolished the potentials of retinoic acid (RA) to down-regulate Cdk2 and Cdk4 and to up-regulate p16, p21, and p27, resulting in activation of E2F1 in the presence of RA. Tretinoin 61-63 cyclin dependent kinase 2 Homo sapiens 82-86 18729080-9 2008 Finally, helenalin increased protein-protein interactions between p21 and cyclin-dependent kinase 2 (Cdk2) which may account in part for the anti-proliferative effect in 3T3-L1 preadipocytes. helenalin 9-18 cyclin dependent kinase 2 Homo sapiens 101-105 18617527-6 2008 Inhibition of Cdk2 (roscovitine) or proteasome (MG132) was associated with an enhanced nuclear punctuate distribution of SHP-1. Roscovitine 20-31 cyclin dependent kinase 2 Homo sapiens 14-18 18838553-8 2008 Finally, decreases in SMRT stability occur in response to the activation of Her2/Neu/ErbB2, and this receptor functions upstream of both Pin1 and Cdk2 in the signaling cascade that regulates SMRT stability and cellular response to tamoxifen. Tamoxifen 231-240 cyclin dependent kinase 2 Homo sapiens 146-150 18769144-4 2008 We showed that chemical agents or siRNA inhibiting the activity of ATM, CDK2 and p70s6K kinases blocked degradation of Delta Np63 alpha in HNSCC cells after cisplatin exposure. Cisplatin 157-166 cyclin dependent kinase 2 Homo sapiens 72-76 18847512-10 2008 CONCLUSIONS: We used methods entailing engineered kinases and thiophosphate enrichment to identify a large number of candidate CDK2 substrates in cell lysates. thiophosphoric acid 62-75 cyclin dependent kinase 2 Homo sapiens 127-131 18567737-4 2008 Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Resveratrol 0-11 cyclin dependent kinase 2 Homo sapiens 164-189 18567737-4 2008 Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Resveratrol 0-11 cyclin dependent kinase 2 Homo sapiens 191-195 18617527-11 2008 Mutational analysis of Tyr(208) and Ser(591) (a Cdk2 phosphorylation site) residues on SHP-1 abolished the expression of the amino-truncated 45-kDa SHP-1 protein. Tyrosine 23-26 cyclin dependent kinase 2 Homo sapiens 48-52 18617527-11 2008 Mutational analysis of Tyr(208) and Ser(591) (a Cdk2 phosphorylation site) residues on SHP-1 abolished the expression of the amino-truncated 45-kDa SHP-1 protein. Serine 36-39 cyclin dependent kinase 2 Homo sapiens 48-52 18790752-2 2008 Ten low molecular weight pharmacologic inhibitors of CDKs are currently in clinical trials against various cancers, including the 2,6,9-trisubstituted purine (R)-roscovitine (CYC202/Seliciclib). 2,6,9-trisubstituted purine 130-157 cyclin dependent kinase 2 Homo sapiens 53-57 18521083-6 2008 During differentiation, the activating phosphorylation site of CDK2 Thr-160 becomes dephosphorylated and cyclins A and E become degraded. Threonine 68-71 cyclin dependent kinase 2 Homo sapiens 63-67 18521083-7 2008 The target for CDK2 kinase in p53 molecule, Ser-315, also becomes dephosphorylated. Serine 44-47 cyclin dependent kinase 2 Homo sapiens 15-19 18296682-4 2008 In addition, naringin treatment strongly induced p21WAF1 expression, independent of the p53 pathway, and downregulated expression of cyclins and cyclin dependent kinases (CDKs). naringin 13-21 cyclin dependent kinase 2 Homo sapiens 171-175 18790752-5 2008 Inhibition of retinoblastoma protein phosphorylation and RNA polymerase II Ser2 phosphorylation in neuroblastoma SH-SY5Y cells exposed to N-&-N1 indicates that N-&-N1 is able to inhibit CDKs in a cellular context. n-& 138-144 cyclin dependent kinase 2 Homo sapiens 194-198 18790752-5 2008 Inhibition of retinoblastoma protein phosphorylation and RNA polymerase II Ser2 phosphorylation in neuroblastoma SH-SY5Y cells exposed to N-&-N1 indicates that N-&-N1 is able to inhibit CDKs in a cellular context. n-& 164-170 cyclin dependent kinase 2 Homo sapiens 194-198 18790752-7 2008 Cocrystal structures of N-&-N1 and (R)-roscovitine in complex with CDK2/cyclin A reveal that both inhibitors adopt similar binding modes. n-& 24-31 cyclin dependent kinase 2 Homo sapiens 71-75 18790752-7 2008 Cocrystal structures of N-&-N1 and (R)-roscovitine in complex with CDK2/cyclin A reveal that both inhibitors adopt similar binding modes. 4-(2-(4-isopropylbenzamido)ethoxy)benzoic acid 31-34 cyclin dependent kinase 2 Homo sapiens 71-75 18790752-2 2008 Ten low molecular weight pharmacologic inhibitors of CDKs are currently in clinical trials against various cancers, including the 2,6,9-trisubstituted purine (R)-roscovitine (CYC202/Seliciclib). Roscovitine 158-173 cyclin dependent kinase 2 Homo sapiens 53-57 18790752-7 2008 Cocrystal structures of N-&-N1 and (R)-roscovitine in complex with CDK2/cyclin A reveal that both inhibitors adopt similar binding modes. Roscovitine 39-54 cyclin dependent kinase 2 Homo sapiens 71-75 18790752-4 2008 N-&-N1 shows exquisite selectivity for CDKs, with 2- to 3-fold enhanced potency compared with (R)-roscovitine. n-& 0-6 cyclin dependent kinase 2 Homo sapiens 43-47 18656911-3 2008 The majority of this paper details the structure-guided optimization of indazole (6) using information gained from multiple ligand-CDK2 cocrystal structures. Indazoles 72-80 cyclin dependent kinase 2 Homo sapiens 131-135 18804536-8 2008 We also found that simvastatin inhibited phosphorylation of Rb, promoted expression of p53, p16, p21, p27 and decreased CDK2/4 activity. Simvastatin 19-30 cyclin dependent kinase 2 Homo sapiens 120-124 18804536-9 2008 In conclusion, simvastatin inhibits VSMC proliferation in high glucose status, mimicking diabetes, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and up-regulation of p53, p21, p16, and p27. Simvastatin 15-26 cyclin dependent kinase 2 Homo sapiens 216-220 18652887-3 2008 DNA flow cytometric analysis indicated that PG induced a G2 phase arrest of the cell cycle in Calu-6 cells at 72 h. PG down-regulated the expression of CDKI (p27), CDK2, CDK4 and CDK6 as well as cyclin D1, and increased cyclin A and cyclin B1 proteins. Pyrogallol 44-46 cyclin dependent kinase 2 Homo sapiens 164-168 18430509-7 2008 Protoapigenone arrested MDAH-2774 and SKOV3 cells at S and G2/M phases via decreasing the expression of p-Cdk2, Cdk2, p-Cyclin B1 and Cyclin B1, as well as increasing the expression of inactive p-Cdc25C. protoapigenone 0-14 cyclin dependent kinase 2 Homo sapiens 106-110 18430509-7 2008 Protoapigenone arrested MDAH-2774 and SKOV3 cells at S and G2/M phases via decreasing the expression of p-Cdk2, Cdk2, p-Cyclin B1 and Cyclin B1, as well as increasing the expression of inactive p-Cdc25C. protoapigenone 0-14 cyclin dependent kinase 2 Homo sapiens 112-116 17960384-0 2008 Combination of all-trans retinoic acid and interferon-gamma upregulated p27(kip1) and down regulated CDK2 to cause cell cycle arrest leading to differentiation and apoptosis in human glioblastoma LN18 (PTEN-proficient) and U87MG (PTEN-deficient) cells. Tretinoin 25-38 cyclin dependent kinase 2 Homo sapiens 101-105 18474441-6 2008 Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. Troglitazone 10-22 cyclin dependent kinase 2 Homo sapiens 136-140 18470542-1 2008 The structures of fully active cyclin-dependent kinase-2 (CDK2) complexed with ATP and peptide substrate, CDK2 after the catalytic reaction, and CDK2 inhibited by phosphorylation at Thr14/Tyr15 were studied using molecular dynamics (MD) simulations. Adenosine Triphosphate 79-82 cyclin dependent kinase 2 Homo sapiens 31-56 18470542-1 2008 The structures of fully active cyclin-dependent kinase-2 (CDK2) complexed with ATP and peptide substrate, CDK2 after the catalytic reaction, and CDK2 inhibited by phosphorylation at Thr14/Tyr15 were studied using molecular dynamics (MD) simulations. Adenosine Triphosphate 79-82 cyclin dependent kinase 2 Homo sapiens 58-62 18470542-5 2008 The inhibitory phosphorylation causes the G-loop to shift from the ATP binding site, which leads to opening of the CDK2 substrate binding box, thus probably weakening substrate binding. Adenosine Triphosphate 67-70 cyclin dependent kinase 2 Homo sapiens 115-119 18583928-6 2008 Using an in vitro splicing assay, we show that phosphorylation of CDC5L at threonines 411 and 438 within recognition sequences for CDKs are required for CDC5L-mediated pre-mRNA splicing. Threonine 75-85 cyclin dependent kinase 2 Homo sapiens 131-135 18494457-3 2008 The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. SCHEMBL3572467 14-67 cyclin dependent kinase 2 Homo sapiens 175-179 18950011-4 2008 Antisense oligonucleotide which directed blocked up the translation site resulted in growth inhibition, downregulation of Stat3, p-Stat3, Cyclins and CDKs, and upregulation of p21 and p27. Oligonucleotides 10-25 cyclin dependent kinase 2 Homo sapiens 150-154 18627125-19 2008 Tyrosine phosphorylation relieves kinase inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue within the flexible C-terminus of p27. Tyrosine 0-8 cyclin dependent kinase 2 Homo sapiens 64-68 18627125-19 2008 Tyrosine phosphorylation relieves kinase inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue within the flexible C-terminus of p27. Threonine 99-108 cyclin dependent kinase 2 Homo sapiens 64-68 18673142-0 2008 3D-QSAR CoMFA and CoMSIA study on benzodipyrazoles as cyclin dependent kinase 2 inhibitors. benzodipyrazoles 34-50 cyclin dependent kinase 2 Homo sapiens 54-79 18673142-2 2008 With the intention of designing compounds with enhanced inhibitory potencies against CDK2, the 3D-QSAR CoMFA and CoMSIA study on benzodipyrazoles series is presented here. benzodipyrazoles 129-145 cyclin dependent kinase 2 Homo sapiens 85-89 18264135-4 2008 Centrosome amplification was dependent on cdk2/cyclin activity since treatment with the small molecule inhibitor SU9516 suppressed centriole reduplication. SU 9516 113-119 cyclin dependent kinase 2 Homo sapiens 42-46 18396144-1 2008 Improvements to phosphopeptide enrichment protocols employing titanium dioxide (TiO2) are described and applied to identification of phosphorylation sites on recombinant human cyclin-dependent kinase 2 (CDK2). titanium dioxide 62-78 cyclin dependent kinase 2 Homo sapiens 176-201 18396144-1 2008 Improvements to phosphopeptide enrichment protocols employing titanium dioxide (TiO2) are described and applied to identification of phosphorylation sites on recombinant human cyclin-dependent kinase 2 (CDK2). titanium dioxide 62-78 cyclin dependent kinase 2 Homo sapiens 203-207 18396144-1 2008 Improvements to phosphopeptide enrichment protocols employing titanium dioxide (TiO2) are described and applied to identification of phosphorylation sites on recombinant human cyclin-dependent kinase 2 (CDK2). titanium dioxide 80-84 cyclin dependent kinase 2 Homo sapiens 176-201 18396144-1 2008 Improvements to phosphopeptide enrichment protocols employing titanium dioxide (TiO2) are described and applied to identification of phosphorylation sites on recombinant human cyclin-dependent kinase 2 (CDK2). titanium dioxide 80-84 cyclin dependent kinase 2 Homo sapiens 203-207 18598164-4 2008 Of the G(1) phase cycle-related proteins examined, the expressions of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 and of cyclin D(1), D(2), and D(3) were found to be markedly reduced by EAPP, whereas cyclin E was unaffected. eapp 190-194 cyclin dependent kinase 2 Homo sapiens 70-101 18544167-7 2008 The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine 15-27 cyclin dependent kinase 2 Homo sapiens 64-68 18495657-6 2008 This effect was associated with a sustained phosphorylation of the cyclin-dependent kinase (CDK)2 at threonine 14 and tyrosine 15 residues, an event that inactivates the CDK2-cyclin complex and blocks S-G(2) phase cell cycle transition. Threonine 101-110 cyclin dependent kinase 2 Homo sapiens 92-97 18495657-6 2008 This effect was associated with a sustained phosphorylation of the cyclin-dependent kinase (CDK)2 at threonine 14 and tyrosine 15 residues, an event that inactivates the CDK2-cyclin complex and blocks S-G(2) phase cell cycle transition. Threonine 101-110 cyclin dependent kinase 2 Homo sapiens 170-174 18495657-6 2008 This effect was associated with a sustained phosphorylation of the cyclin-dependent kinase (CDK)2 at threonine 14 and tyrosine 15 residues, an event that inactivates the CDK2-cyclin complex and blocks S-G(2) phase cell cycle transition. Tyrosine 118-126 cyclin dependent kinase 2 Homo sapiens 170-174 18495657-7 2008 Consistently, mesalazine reduced the protein content of CDC25A, a phosphatase that regulates CDK2 phosphorylation status. Mesalamine 14-24 cyclin dependent kinase 2 Homo sapiens 93-97 18519679-9 2008 In these cells, cyclin-dependent kinase (Cdk)-4 and Cdk2 activities were affected by Mel-18, which were mediated by changes in cyclin D1 expression and p27(Kip1) phosphorylation at Thr(157), but not by INK4a/ARF genes. Threonine 181-184 cyclin dependent kinase 2 Homo sapiens 52-56 18446845-6 2008 ESS-mediated G2/M arrest was found to be associated with up-regulation of cyclin A, Cdc2, tumor suppressor p53 and cyclin dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), whereas the expressions of other G2/M regulatory proteins, including cyclin B1 and Cdk2, were down-regulated compared with the control. ESS 0-3 cyclin dependent kinase 2 Homo sapiens 254-258 18337475-3 2008 Blockade of cell cycle by protoapigenone was associated with an increase in the levels of inactivated phospho (p)-Cdc25C (Ser216) and a decrease in the levels of activated p-cyclin B1 (Ser147), cyclin B1, and cyclin-dependent kinase (Cdk) 2. protoapigenone 26-40 cyclin dependent kinase 2 Homo sapiens 209-240 18337475-7 2008 In contrast, p38 MAPK, but not JNK1/2, was involved in the protoapigenone-mediated S and G(2)/M arrest by modulating the levels of Cdk2 and p-Cdc25C (Ser216). protoapigenone 59-73 cyclin dependent kinase 2 Homo sapiens 131-135 18402936-5 2008 Furthermore, in terms of the effects of YSK2821 on cell cycle-related proteins, YSK2821 enhanced the expression of the cyclin-dependent protein kinase (CDK) inhibitor p27 and down-regulated CDK2 and cyclin E expression, but did not affect CDK4 and cyclin D1 expression. YSK 2821 40-47 cyclin dependent kinase 2 Homo sapiens 152-155 18402936-5 2008 Furthermore, in terms of the effects of YSK2821 on cell cycle-related proteins, YSK2821 enhanced the expression of the cyclin-dependent protein kinase (CDK) inhibitor p27 and down-regulated CDK2 and cyclin E expression, but did not affect CDK4 and cyclin D1 expression. YSK 2821 80-87 cyclin dependent kinase 2 Homo sapiens 152-155 18402936-5 2008 Furthermore, in terms of the effects of YSK2821 on cell cycle-related proteins, YSK2821 enhanced the expression of the cyclin-dependent protein kinase (CDK) inhibitor p27 and down-regulated CDK2 and cyclin E expression, but did not affect CDK4 and cyclin D1 expression. YSK 2821 80-87 cyclin dependent kinase 2 Homo sapiens 190-194 18353638-2 2008 Potent inhibitors against CDK1 and CDK2 were obtained by introduction of 1lambda(6)-isothiazolidine-1,1-dioxide at 5-position of indazole. 1lambda(6)-isothiazolidine-1,1-dioxide 73-111 cyclin dependent kinase 2 Homo sapiens 35-39 18408738-5 2008 NaBT decreased cyclin-dependent kinase CDK2 activity and induced p27 Kip1 expression; inhibition of GSK-3 rescued NaBT-inhibited CDK2 activity and blocked NaBT-induced p27 Kip1 expression in the nucleus but not in the cytoplasm. NABT 0-4 cyclin dependent kinase 2 Homo sapiens 39-43 18408738-5 2008 NaBT decreased cyclin-dependent kinase CDK2 activity and induced p27 Kip1 expression; inhibition of GSK-3 rescued NaBT-inhibited CDK2 activity and blocked NaBT-induced p27 Kip1 expression in the nucleus but not in the cytoplasm. NABT 114-118 cyclin dependent kinase 2 Homo sapiens 129-133 18408738-5 2008 NaBT decreased cyclin-dependent kinase CDK2 activity and induced p27 Kip1 expression; inhibition of GSK-3 rescued NaBT-inhibited CDK2 activity and blocked NaBT-induced p27 Kip1 expression in the nucleus but not in the cytoplasm. NABT 114-118 cyclin dependent kinase 2 Homo sapiens 129-133 18408738-7 2008 Furthermore, NaBT increased p27 Kip1 binding to CDK2, which was completely abolished by GSK-3 inhibition. NABT 13-17 cyclin dependent kinase 2 Homo sapiens 48-52 18276582-4 2008 Coexpression of SV40 small t antigen (st), but not other tested oncogenes, efficiently induces mitogen-independent CDK2 phosphorylation on Thr-160, CDK2 activation, and DNA synthesis. Threonine 139-142 cyclin dependent kinase 2 Homo sapiens 115-119 18183483-1 2008 The proline-directed serine threonine kinase, Cdk5, is an unusual molecule that belongs to the well-known large family of proteins, cyclin-dependent kinases (Cdks). Proline 4-11 cyclin dependent kinase 2 Homo sapiens 158-162 18183483-1 2008 The proline-directed serine threonine kinase, Cdk5, is an unusual molecule that belongs to the well-known large family of proteins, cyclin-dependent kinases (Cdks). Serine 21-27 cyclin dependent kinase 2 Homo sapiens 158-162 18202593-7 2008 Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21(WAF1/CIP1), and enhanced interaction of p21(WAF1/CIP1) with cyclin-dependent kinase 2, eventually inhibiting its activity. Medroxyprogesterone Acetate 0-27 cyclin dependent kinase 2 Homo sapiens 150-175 18202593-8 2008 CONCLUSIONS: Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. Medroxyprogesterone Acetate 13-40 cyclin dependent kinase 2 Homo sapiens 133-158 18321631-5 2008 Cdc25A down-regulation by RNA interference (RNAi) prolonged the S-phase arrest induced by BaP and decreased clearly the expression levels of cyclin A and cyclin E. Therefore, our results further demonstrated that Cdc25A was an effector in Chk1-Cdc25A-cyclin A/Cdk2 pathway of S-phase checkpoint elicited by the carcinogen BaP in 16HBE cells. Benzo(a)pyrene 90-93 cyclin dependent kinase 2 Homo sapiens 260-264 18321631-5 2008 Cdc25A down-regulation by RNA interference (RNAi) prolonged the S-phase arrest induced by BaP and decreased clearly the expression levels of cyclin A and cyclin E. Therefore, our results further demonstrated that Cdc25A was an effector in Chk1-Cdc25A-cyclin A/Cdk2 pathway of S-phase checkpoint elicited by the carcinogen BaP in 16HBE cells. Benzo(a)pyrene 322-325 cyclin dependent kinase 2 Homo sapiens 260-264 18379040-5 2008 Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins. Berberine 38-47 cyclin dependent kinase 2 Homo sapiens 151-182 18353638-2 2008 Potent inhibitors against CDK1 and CDK2 were obtained by introduction of 1lambda(6)-isothiazolidine-1,1-dioxide at 5-position of indazole. Indazoles 129-137 cyclin dependent kinase 2 Homo sapiens 35-39 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Docetaxel 411-420 cyclin dependent kinase 2 Homo sapiens 103-107 18239466-5 2008 Our data show that Serine-59 regulates Sp1 proteolytic processing, and thereby provides a mechanism for the upregulation of Sp1-dependent transcription by CyclinA/cdk2 phosphorylation of Serine-59. Serine 19-25 cyclin dependent kinase 2 Homo sapiens 163-167 18413795-1 2008 AG-012986 is a multitargeted cyclin-dependent kinase (CDK) inhibitor active against CDK1, CDK2, CDK4/6, CDK5, and CDK9, with selectivity over a diverse panel of non-CDK kinases. AG-012986 0-9 cyclin dependent kinase 2 Homo sapiens 90-94 18356301-0 2008 ATP-dependent activation of p21WAF1/CIP1-associated Cdk2 by Cdc6. Adenosine Triphosphate 0-3 cyclin dependent kinase 2 Homo sapiens 52-56 18356301-3 2008 Here, we report that Cdc6 protein can activate p21-associated Cdk2 in an ATP-dependent manner in vitro. Adenosine Triphosphate 73-76 cyclin dependent kinase 2 Homo sapiens 62-66 18332217-3 2008 We identify on protein expression arrays novel cyclin E-Cdk2 substrates, including SIRT2, a member of the Sirtuin family of NAD(+)-dependent deacetylases that targets alpha-tubulin. NAD 124-130 cyclin dependent kinase 2 Homo sapiens 56-60 18332217-4 2008 We define Ser-331 as the site phosphorylated by cyclin E-Cdk2, cyclin A-Cdk2, and p35-Cdk5 both in vitro and in cells. Serine 10-13 cyclin dependent kinase 2 Homo sapiens 57-61 18332217-4 2008 We define Ser-331 as the site phosphorylated by cyclin E-Cdk2, cyclin A-Cdk2, and p35-Cdk5 both in vitro and in cells. Serine 10-13 cyclin dependent kinase 2 Homo sapiens 72-76 18354084-2 2008 Akt phosphorylates CDK2 at threonine 39 residue both in vitro and in vivo. Threonine 27-36 cyclin dependent kinase 2 Homo sapiens 19-23 18354084-3 2008 Although CDK2 threonine 39 phosphorylation mediated by Akt enhances cyclin-A binding, it is dispensable for its basal binding and the kinase activity. Threonine 14-23 cyclin dependent kinase 2 Homo sapiens 9-13 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Methotrexate 394-406 cyclin dependent kinase 2 Homo sapiens 4-8 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Methotrexate 394-406 cyclin dependent kinase 2 Homo sapiens 103-107 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Methotrexate 394-406 cyclin dependent kinase 2 Homo sapiens 103-107 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Docetaxel 411-420 cyclin dependent kinase 2 Homo sapiens 4-8 18354084-6 2008 The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Docetaxel 411-420 cyclin dependent kinase 2 Homo sapiens 103-107 18239466-5 2008 Our data show that Serine-59 regulates Sp1 proteolytic processing, and thereby provides a mechanism for the upregulation of Sp1-dependent transcription by CyclinA/cdk2 phosphorylation of Serine-59. Serine 187-193 cyclin dependent kinase 2 Homo sapiens 163-167 18232649-0 2008 Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. meriolins 0-9 cyclin dependent kinase 2 Homo sapiens 121-125 18288380-7 2008 Apicidin attenuated the expression of cyclin E and CDK2 in MCF10A cells, decreased cyclin D1 and cyclin E levels in MCF10A-ras cells, and increased the levels of CDK inhibitors, p21WAF1/Cip1 and p27Kip1, in both cell lines. apicidin 0-8 cyclin dependent kinase 2 Homo sapiens 51-55 18307332-5 2008 The performance of GANDI is tested on cyclin-dependent kinase 2 (CDK2) using a library of about 14 000 fragments and the binding mode of a known oxindole inhibitor to bias the design. 2-oxindole 145-153 cyclin dependent kinase 2 Homo sapiens 38-63 18307332-5 2008 The performance of GANDI is tested on cyclin-dependent kinase 2 (CDK2) using a library of about 14 000 fragments and the binding mode of a known oxindole inhibitor to bias the design. 2-oxindole 145-153 cyclin dependent kinase 2 Homo sapiens 65-69 18307332-6 2008 Top ranking GANDI molecules are involved in one to three hydrogen bonds with the backbone polar groups in the hinge region of CDK2, an interaction pattern observed in potent kinase inhibitors. Hydrogen 57-65 cyclin dependent kinase 2 Homo sapiens 126-130 18307332-7 2008 Notably, a GANDI molecule with very favorable predicted binding affinity shares a 2-N-phenyl-1,3-thiazole-2,4-diamine moiety with a known nanomolar inhibitor of CDK2. Kinome_1250 82-117 cyclin dependent kinase 2 Homo sapiens 161-165 18232649-8 2008 Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease. meriolins 0-9 cyclin dependent kinase 2 Homo sapiens 164-168 18232649-0 2008 Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. 3-(pyrimidin-4-yl)-7-azaindoles 11-42 cyclin dependent kinase 2 Homo sapiens 121-125 18232649-0 2008 Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. meriolin 135-143 cyclin dependent kinase 2 Homo sapiens 121-125 18232649-2 2008 Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). meriolins 0-9 cyclin dependent kinase 2 Homo sapiens 80-84 18232649-4 2008 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. Adenosine Triphosphate 131-134 cyclin dependent kinase 2 Homo sapiens 37-41 18232649-7 2008 Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. meriolins 25-34 cyclin dependent kinase 2 Homo sapiens 62-66 18383818-8 2008 CDK2 protein and Thr-160 phosphorylated CDK2 were remarkably reduced in the resistant cell lines. Threonine 17-20 cyclin dependent kinase 2 Homo sapiens 40-44 18202766-5 2008 Consistently, Roscovitine, an inhibitor of CDK2, induced cell cycle arrest in normally proliferating cells and a chemical inhibitor of CDK4, 3-ATA [3-Amino-9-thio(10H)-acridone], was found to induce growth arrest. Roscovitine 14-25 cyclin dependent kinase 2 Homo sapiens 43-47 18202766-5 2008 Consistently, Roscovitine, an inhibitor of CDK2, induced cell cycle arrest in normally proliferating cells and a chemical inhibitor of CDK4, 3-ATA [3-Amino-9-thio(10H)-acridone], was found to induce growth arrest. 3-amino-10H-acridine-9-thione 141-146 cyclin dependent kinase 2 Homo sapiens 43-47 18295547-2 2008 Our data suggest that DPTH inhibits human umbilical venous endothelial cells (HUVEC) proliferation by increasing the level of p21 protein, which in turn inhibits the activities of cyclin-dependent kinase (CDK)2 and CDK4, and finally interrupts the cell cycle. diphenylthiohydantoin 22-26 cyclin dependent kinase 2 Homo sapiens 205-210 18063365-0 2008 A flavonoid gossypin binds to cyclin-dependent kinase 2. Flavonoids 2-11 cyclin dependent kinase 2 Homo sapiens 30-55 18063365-0 2008 A flavonoid gossypin binds to cyclin-dependent kinase 2. gossypin 12-20 cyclin dependent kinase 2 Homo sapiens 30-55 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-27 cyclin dependent kinase 2 Homo sapiens 36-61 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-27 cyclin dependent kinase 2 Homo sapiens 63-67 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-27 cyclin dependent kinase 2 Homo sapiens 158-162 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-26 cyclin dependent kinase 2 Homo sapiens 36-61 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-26 cyclin dependent kinase 2 Homo sapiens 63-67 18063365-2 2008 In order to find flavonoids showing cyclin-dependent kinase 2 (CDK2) binding effects, 347 flavonoid derivatives were docked into the crystal structure of the CDK2. Flavonoids 17-26 cyclin dependent kinase 2 Homo sapiens 158-162 18063365-3 2008 The docking study showed that gossypin has a good conformational match with CDK2, which was confirmed by the binding affinity assay using NMR experiments. gossypin 30-38 cyclin dependent kinase 2 Homo sapiens 76-80 18006504-2 2008 In this study, RA is found to cause MAPK activation with sustained association of RAF to MEK or ERK, leading to a MAPK-dependent accumulation of p21(Waf1/Cip1) and binding to CDK2 blocking G(1)/S transition. Tretinoin 15-17 cyclin dependent kinase 2 Homo sapiens 175-179 17997402-5 2008 Furthermore, M cyclin directed cdk2 to phosphorylate p27(Kip1) on threonine 187 (T187) and cellular expression of M cyclin led to down-regulation of p27(Kip1) and the partial subversion of the associated G1 arrest. Threonine 66-75 cyclin dependent kinase 2 Homo sapiens 31-35 17942543-4 2008 To examine the role of cyclin-dependent kinases (cdks) in the establishment of this site, we used roscovitine, a specific inhibitor of cdk1, cdk2, cdk7, and cdk9, that alters processing of viral IE transcripts and inhibits expression of viral early genes. Roscovitine 98-109 cyclin dependent kinase 2 Homo sapiens 141-145 17959232-9 2008 Furthermore, DPF provoked S phase arrest in SKOV-3 cells with down-regulation of cyclin A, E, D1 and CDK2. diethyl phosphate 13-16 cyclin dependent kinase 2 Homo sapiens 101-105 17928568-8 2008 SIM induces a partial blockade of retinoblastoma protein phosphorylation and inhibition of cyclin E/cyclin-dependent kinase (CDK)2 activity associated with increased levels of the CDK inhibitors p21(Cip1) and p27(kip1). Simvastatin 0-3 cyclin dependent kinase 2 Homo sapiens 100-130 17928568-8 2008 SIM induces a partial blockade of retinoblastoma protein phosphorylation and inhibition of cyclin E/cyclin-dependent kinase (CDK)2 activity associated with increased levels of the CDK inhibitors p21(Cip1) and p27(kip1). Simvastatin 0-3 cyclin dependent kinase 2 Homo sapiens 125-128 18773862-6 2008 Consistent with the inhibition effect and G1 arrest, ATRA and SB, alone or in combination, induced the expression of G1 phase markers cyclin-dependent kinase (CDK) 6, p21, and p27; inhibited the expression of S-G2 phase proteins CDK2; and decreased Rb phosphorylation. Tretinoin 53-57 cyclin dependent kinase 2 Homo sapiens 229-233 18773862-6 2008 Consistent with the inhibition effect and G1 arrest, ATRA and SB, alone or in combination, induced the expression of G1 phase markers cyclin-dependent kinase (CDK) 6, p21, and p27; inhibited the expression of S-G2 phase proteins CDK2; and decreased Rb phosphorylation. Butyric Acid 62-64 cyclin dependent kinase 2 Homo sapiens 229-233 18773862-9 2008 These results indicate that the growth inhibition and G1 arrest of oral squamous carcinoma cells in response to ATRA and/or SB correlates with the induction of G1 phase cell cycle regulatory proteins CDK6, p21, and p27 and the inhibition of S-G2 phase cell cycle regulatory protein CDK2. Tretinoin 112-116 cyclin dependent kinase 2 Homo sapiens 282-286 18773862-9 2008 These results indicate that the growth inhibition and G1 arrest of oral squamous carcinoma cells in response to ATRA and/or SB correlates with the induction of G1 phase cell cycle regulatory proteins CDK6, p21, and p27 and the inhibition of S-G2 phase cell cycle regulatory protein CDK2. Butyric Acid 124-126 cyclin dependent kinase 2 Homo sapiens 282-286 17975794-4 2007 The present article shows that olomoucine (OLO), a weak CDK2 inhibitor has new, unexpected activity. olomoucine 31-41 cyclin dependent kinase 2 Homo sapiens 56-60 17975794-4 2007 The present article shows that olomoucine (OLO), a weak CDK2 inhibitor has new, unexpected activity. olomoucine 43-46 cyclin dependent kinase 2 Homo sapiens 56-60 17697781-3 2007 Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. Urea 8-12 cyclin dependent kinase 2 Homo sapiens 96-100 17599054-4 2007 We present the first investigation of the therapeutic potential of CDK inhibitors, using the guanine-based CDK inhibitor NU2058 (CDK2 IC(50)=17 microM, CDK1 IC(50)=26 microM), in comparison with the antiandrogen bicalutamide (Casodex) in AIPC cells. Guanine 93-100 cyclin dependent kinase 2 Homo sapiens 129-133 17599054-4 2007 We present the first investigation of the therapeutic potential of CDK inhibitors, using the guanine-based CDK inhibitor NU2058 (CDK2 IC(50)=17 microM, CDK1 IC(50)=26 microM), in comparison with the antiandrogen bicalutamide (Casodex) in AIPC cells. NU2058 121-127 cyclin dependent kinase 2 Homo sapiens 129-133 18156799-3 2007 Here, we evaluated the in vitro cytotoxic activity of the cdk2 inhibitor CVT-313 against several human DLBCL cells. CVT 313 73-80 cyclin dependent kinase 2 Homo sapiens 58-62 18156799-9 2007 Further, cdk2 inhibition led to decreased Mcl-1 mRNA levels, which was proceeded by reduced phosphorylation of serine 2 on the carboxyl terminal domain (CTD) of RNA polymerase II. serine 2 111-119 cyclin dependent kinase 2 Homo sapiens 9-13 18088467-10 2007 In addition, 8-Cl-cAMP was able to inhibit the cell growth through modulating expression of cell cycle regulators CDK2 and cyclin E. It is concluded that 8-cl-cAMP inhibits the proliferation and induce apoptosis of multiple myeloma cells effectively. 8-chloro-cyclic adenosine monophosphate 13-22 cyclin dependent kinase 2 Homo sapiens 114-118 18088467-10 2007 In addition, 8-Cl-cAMP was able to inhibit the cell growth through modulating expression of cell cycle regulators CDK2 and cyclin E. It is concluded that 8-cl-cAMP inhibits the proliferation and induce apoptosis of multiple myeloma cells effectively. 8-chloro-cyclic adenosine monophosphate 154-163 cyclin dependent kinase 2 Homo sapiens 114-118 17726381-6 2007 Following the identification of this active sequence, here we propose a computer-generated three-dimensional model of the interaction between the Cdk2/Cyclin A complex and the N-terminal nine-amino acid sequence of the Spa310 peptide. spa310 219-225 cyclin dependent kinase 2 Homo sapiens 146-150 17804818-5 2007 When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. Alanine 66-73 cyclin dependent kinase 2 Homo sapiens 7-11 17631934-2 2007 Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Deferoxamine 24-27 cyclin dependent kinase 2 Homo sapiens 170-194 17631934-2 2007 Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Deferoxamine 24-27 cyclin dependent kinase 2 Homo sapiens 196-200 17631934-2 2007 Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone 32-84 cyclin dependent kinase 2 Homo sapiens 170-194 17631934-2 2007 Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone 32-84 cyclin dependent kinase 2 Homo sapiens 196-200 17631934-3 2007 Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Iron 132-136 cyclin dependent kinase 2 Homo sapiens 31-35 17631934-3 2007 Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Iron 132-136 cyclin dependent kinase 2 Homo sapiens 124-128 17631934-9 2007 In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Iron 53-57 cyclin dependent kinase 2 Homo sapiens 116-120 17869226-6 2007 In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. dhts 13-17 cyclin dependent kinase 2 Homo sapiens 53-57 18056467-3 2007 When exposed to the antiestrogen ICI 182780, these cells accumulate in G(1) by reducing the expression of Cks1, and increasing the levels of p130/Rb2, a cdk2 inhibitor and SCF(Skp2) target. ici 33-36 cyclin dependent kinase 2 Homo sapiens 153-157 17904366-2 2007 From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors. pyrazolo(1,5-a)pyrimidine 47-72 cyclin dependent kinase 2 Homo sapiens 181-185 17977533-5 2007 Accordingly, we provide the evidence that PM induces AEC G1 arrest by altered regulation of G1 cyclins and CDKs. Promethium 42-44 cyclin dependent kinase 2 Homo sapiens 107-111 17697781-3 2007 Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. Urea 89-93 cyclin dependent kinase 2 Homo sapiens 96-100 17697781-3 2007 Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. 3,4-dihydroquinazolin-2(1h)-ones 146-178 cyclin dependent kinase 2 Homo sapiens 96-100 17438528-5 2007 This mechanism was initially identified in cells treated with the peptide vinyl sulfone proteasome inhibitor Z-L(3)VS. We subsequently found that the formation of more than one daughter at maternal centrioles requires cyclin E/cyclin-dependent kinase 2 as well as Polo-like kinase 4 and that overexpression of these proteins mimics this phenotype in the absence of a proteasome inhibitor. z-l 109-112 cyclin dependent kinase 2 Homo sapiens 227-252 17602833-8 2007 Cdk-2 phosphorylates Thr(187)-p27, and immunoblotting demonstrated that cyclopamine treatment of PC-3 cells reduces the expression of cdk-2. Threonine 21-24 cyclin dependent kinase 2 Homo sapiens 0-5 17602833-8 2007 Cdk-2 phosphorylates Thr(187)-p27, and immunoblotting demonstrated that cyclopamine treatment of PC-3 cells reduces the expression of cdk-2. cyclopamine 72-83 cyclin dependent kinase 2 Homo sapiens 0-5 17602833-8 2007 Cdk-2 phosphorylates Thr(187)-p27, and immunoblotting demonstrated that cyclopamine treatment of PC-3 cells reduces the expression of cdk-2. cyclopamine 72-83 cyclin dependent kinase 2 Homo sapiens 134-139 18156791-3 2007 A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. 6-bromo-2,3,4,9-tetrahydrocarbolin-1-one 97-102 cyclin dependent kinase 2 Homo sapiens 76-80 18156791-4 2007 This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Adenosine Triphosphate 141-144 cyclin dependent kinase 2 Homo sapiens 48-52 18156791-4 2007 This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Adenosine Triphosphate 141-144 cyclin dependent kinase 2 Homo sapiens 163-167 18156791-4 2007 This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Hydrogen 185-193 cyclin dependent kinase 2 Homo sapiens 48-52 18156791-4 2007 This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Hydrogen 185-193 cyclin dependent kinase 2 Homo sapiens 163-167 17696482-10 2007 Pterostilbene increased the p53, p21, p27, and p16 proteins and decreased levels of cyclin A, cyclin E, cyclin-dependent kinase 2 (Cdk2), Cdk4, and Cdk6, but the expression of cyclin D1 was not affected. pterostilbene 0-13 cyclin dependent kinase 2 Homo sapiens 104-129 17696482-10 2007 Pterostilbene increased the p53, p21, p27, and p16 proteins and decreased levels of cyclin A, cyclin E, cyclin-dependent kinase 2 (Cdk2), Cdk4, and Cdk6, but the expression of cyclin D1 was not affected. pterostilbene 0-13 cyclin dependent kinase 2 Homo sapiens 131-135 17639507-7 2007 Conversely, the malignant SP was of undetermined acinar origin and with a complete loss of expression of the CDK2 inhibitor p21(WAF1/Cip1). sp 26-28 cyclin dependent kinase 2 Homo sapiens 109-113 17713901-2 2007 In the present paper, eight Molecular Dynamics (MD) simulations are carried out to examine the importance of structure and dynamics of water in the active site of both CDK2 and CDK5 complexes with roscovitine and indirubin analogues. Water 135-140 cyclin dependent kinase 2 Homo sapiens 168-172 17970072-8 2007 Sodium butyrate also significantly decreased the expression of the cell cycle regulatory proteins (cyclin D1/cyclin dependent kinase (CDK)4, CDK6, and cyclin E/CDK2) in the LNCaP cells after 48 h treatment. Butyric Acid 0-15 cyclin dependent kinase 2 Homo sapiens 160-164 17804748-5 2007 A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. meriolins 78-87 cyclin dependent kinase 2 Homo sapiens 153-157 17634406-4 2007 Among the G1 phase cell cycle-related proteins, the levels of cyclin-dependent protein kinase (CDK)2, CDK6, cyclin D1, cyclin D2, cyclin D3 and cyclin E were reduced by acteoside, whereas the steady-state level of CDK4 was unaffected. acteoside 169-178 cyclin dependent kinase 2 Homo sapiens 95-100 17634406-6 2007 In addition, acteoside markedly enhanced the binding of p21(CIP1/WAF1) and p27(KIP1) to CDK4 and CDK6, resulting in the reduction of CDK2, CDK4 and CDK6 activities. acteoside 13-22 cyclin dependent kinase 2 Homo sapiens 133-137 17634406-9 2007 In conclusion, the onset of acteoside-induced G1 arrest of HL-60 cells prior to the differentiation appears to be tightly linked to up-regulation of the p21(CIP1/WAF1) and p27(KIP1) levels and decreases in the CDK2, CDK4 and CDK6 activities. acteoside 28-37 cyclin dependent kinase 2 Homo sapiens 210-214 17713901-2 2007 In the present paper, eight Molecular Dynamics (MD) simulations are carried out to examine the importance of structure and dynamics of water in the active site of both CDK2 and CDK5 complexes with roscovitine and indirubin analogues. Roscovitine 197-208 cyclin dependent kinase 2 Homo sapiens 168-172 17713901-2 2007 In the present paper, eight Molecular Dynamics (MD) simulations are carried out to examine the importance of structure and dynamics of water in the active site of both CDK2 and CDK5 complexes with roscovitine and indirubin analogues. indirubin 213-222 cyclin dependent kinase 2 Homo sapiens 168-172 17713901-3 2007 Together with previous results, the current work shows a highly conserved water-involved hydrogen bonding (HB) network in both CDK2- and CDK5-indirubin combinations to complete information from the X-ray crystallography. Water 74-79 cyclin dependent kinase 2 Homo sapiens 127-131 17713901-3 2007 Together with previous results, the current work shows a highly conserved water-involved hydrogen bonding (HB) network in both CDK2- and CDK5-indirubin combinations to complete information from the X-ray crystallography. Hydrogen 89-97 cyclin dependent kinase 2 Homo sapiens 127-131 17713901-5 2007 Different binding patterns of roscovitine in CDK2 and CDK5 are detected during the simulations because of the different binding conformations of the group on the C2 side chain, which might offer a clue toward finding highly selective inhibitors with regards to CDK2 and CDK5. Roscovitine 30-41 cyclin dependent kinase 2 Homo sapiens 45-49 17713901-5 2007 Different binding patterns of roscovitine in CDK2 and CDK5 are detected during the simulations because of the different binding conformations of the group on the C2 side chain, which might offer a clue toward finding highly selective inhibitors with regards to CDK2 and CDK5. Roscovitine 30-41 cyclin dependent kinase 2 Homo sapiens 261-265 17456787-2 2007 Here, we demonstrate that erlotinib-induced cell growth inhibition in EGFR high-expressing human H322 NSCLC cells was accompanied by G1/S phase arrest, which was largely caused by a decrease in expression of G1/S-related cyclins, suppression of activities of cyclin-dependent kinase (CDK) 2 and CDK4, induction of CDK inhibitor p27(KIP1), and retinoblastoma hypophosphorylation. Erlotinib Hydrochloride 26-35 cyclin dependent kinase 2 Homo sapiens 259-290 17545210-5 2007 Coimmunoprecipitation experiments confirm that cyclin E-cdk2 is more phosphorylated at Thr14 and Tyr15 in the presence of arsenite, and kinase activity assays reveal a decrease in cyclin E-associated cdk2 activity. arsenite 122-130 cyclin dependent kinase 2 Homo sapiens 56-60 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 148-173 cyclin dependent kinase 2 Homo sapiens 17-42 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 148-173 cyclin dependent kinase 2 Homo sapiens 44-49 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 148-173 cyclin dependent kinase 2 Homo sapiens 250-255 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 175-179 cyclin dependent kinase 2 Homo sapiens 17-42 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 175-179 cyclin dependent kinase 2 Homo sapiens 44-49 17655502-2 2007 Considering that cyclin-dependent kinase-2 (CDK-2) performs essential functions for cellular proliferation, our aim was to test the hypothesis that l-3,3",5-triiodothyronine (T(3)) stimulates liver cell proliferation by upstream mechanisms involving CDK-2 expression dependent on Kupffer cell signaling. Triiodothyronine 175-179 cyclin dependent kinase 2 Homo sapiens 250-255 17655502-6 2007 We conclude that T(3) administration triggers liver CDK-2 expression and cellular proliferation through a cascade associated with Kupffer cell-dependent TNF-alpha generation, JNK phosphorylation, and AP-1 activation. Triiodothyronine 17-21 cyclin dependent kinase 2 Homo sapiens 52-57 17655502-7 2007 Since CDK-2 promotes phase S progression within the cell cycle, this response may constitute a major mechanism involved in T(3)-induced liver preconditioning to ischemia/reperfusion injury. Triiodothyronine 123-127 cyclin dependent kinase 2 Homo sapiens 6-11 17507429-8 2007 Testosterone significantly reduced kinase activity of CDK2 and -6, but not CDK4, -7, or -1. Testosterone 0-12 cyclin dependent kinase 2 Homo sapiens 54-65 17601773-8 2007 Mass spectrometric analysis revealed that cdk2/cyclinA phosphorylates C/EBPbeta on Thr(188) and is required for phosphorylation (on Ser(184) or Thr(179)) of C/EBPbeta by GSK3beta and maintenance of DNA binding activity. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 42-46 17671085-0 2007 Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity. Erlotinib Hydrochloride 38-47 cyclin dependent kinase 2 Homo sapiens 59-84 17671085-5 2007 However, suppression of CDK2 activity after erlotinib treatment correlated with erlotinib sensitivity (P < 0.0001). Erlotinib Hydrochloride 44-53 cyclin dependent kinase 2 Homo sapiens 24-28 17671085-5 2007 However, suppression of CDK2 activity after erlotinib treatment correlated with erlotinib sensitivity (P < 0.0001). Erlotinib Hydrochloride 80-89 cyclin dependent kinase 2 Homo sapiens 24-28 17671085-6 2007 Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. Erlotinib Hydrochloride 74-83 cyclin dependent kinase 2 Homo sapiens 15-19 17671085-6 2007 Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. Erlotinib Hydrochloride 98-107 cyclin dependent kinase 2 Homo sapiens 15-19 17671085-6 2007 Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. Erlotinib Hydrochloride 98-107 cyclin dependent kinase 2 Homo sapiens 230-234 17671085-6 2007 Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. Erlotinib Hydrochloride 98-107 cyclin dependent kinase 2 Homo sapiens 15-19 17671085-6 2007 Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. Erlotinib Hydrochloride 98-107 cyclin dependent kinase 2 Homo sapiens 230-234 17671085-9 2007 These findings indicate that the ability of erlotinib to suppress CDK2 activity is critical for cellular sensitivity to erlotinib, regardless of EGFR expression level, and that the presence of p27 in the cytoplasm also participates in erlotinib resistance. Erlotinib Hydrochloride 44-53 cyclin dependent kinase 2 Homo sapiens 66-70 17671085-9 2007 These findings indicate that the ability of erlotinib to suppress CDK2 activity is critical for cellular sensitivity to erlotinib, regardless of EGFR expression level, and that the presence of p27 in the cytoplasm also participates in erlotinib resistance. Erlotinib Hydrochloride 120-129 cyclin dependent kinase 2 Homo sapiens 66-70 17671085-9 2007 These findings indicate that the ability of erlotinib to suppress CDK2 activity is critical for cellular sensitivity to erlotinib, regardless of EGFR expression level, and that the presence of p27 in the cytoplasm also participates in erlotinib resistance. Erlotinib Hydrochloride 120-129 cyclin dependent kinase 2 Homo sapiens 66-70 17601773-8 2007 Mass spectrometric analysis revealed that cdk2/cyclinA phosphorylates C/EBPbeta on Thr(188) and is required for phosphorylation (on Ser(184) or Thr(179)) of C/EBPbeta by GSK3beta and maintenance of DNA binding activity. Serine 132-135 cyclin dependent kinase 2 Homo sapiens 42-46 17601773-8 2007 Mass spectrometric analysis revealed that cdk2/cyclinA phosphorylates C/EBPbeta on Thr(188) and is required for phosphorylation (on Ser(184) or Thr(179)) of C/EBPbeta by GSK3beta and maintenance of DNA binding activity. Threonine 144-147 cyclin dependent kinase 2 Homo sapiens 42-46 17601773-10 2007 Thus, MAPK and cdk2/cyclinA act sequentially to maintain Thr(188) of C/EBPbeta in the primed phosphorylated state during MCE and thereby progression of terminal differentiation. Threonine 57-60 cyclin dependent kinase 2 Homo sapiens 15-19 17389612-4 2007 In the studies examining changes in cell cycle and apoptosis regulators, isosilybin B and isosilybin A resulted in a decrease in the levels of both cyclins (D1, D3, E and A) and cyclin-dependent kinases (Cdk2, Cdk4 and cell division cycle 25A), but caused an increase in p21, p27 and p53 levels, except in 22Rv1 cells where isosilybin B caused a decrease in p21 protein level. isosilybin A 73-85 cyclin dependent kinase 2 Homo sapiens 204-208 17252195-2 2007 Here, we show that upregulated Cyclin A/Cdk2 activity precedes the proteolytic cleavage of PARP and is correlated with the mitochondrial translocation of Bax and the loss of mitochondrial transmembrane potential (Deltapsim) during etoposide-induced apoptosis in human cervical adenocarcinoma (HeLa) cells. Etoposide 231-240 cyclin dependent kinase 2 Homo sapiens 40-44 17252195-3 2007 Etoposide-induced apoptotic cell death is efficiently prevented in cells that overexpress a dominant negative mutant of Cdk2 (Cdk2-dn) or p21(WAF1/CIP1), a specific Cdk inhibitor. Etoposide 0-9 cyclin dependent kinase 2 Homo sapiens 120-124 17252195-3 2007 Etoposide-induced apoptotic cell death is efficiently prevented in cells that overexpress a dominant negative mutant of Cdk2 (Cdk2-dn) or p21(WAF1/CIP1), a specific Cdk inhibitor. Etoposide 0-9 cyclin dependent kinase 2 Homo sapiens 126-130 17252195-5 2007 Disruption of the mitochondrial transmembrane potential in etoposide-induced cells is prevented in cells that overexpress Cdk2-dn or p21(WAF1/CIP1), while this transition is prominently promoted in Cyclin A-expressing cells. Etoposide 59-68 cyclin dependent kinase 2 Homo sapiens 122-126 17252195-6 2007 We screened for mitochondrial Cdk2 targets in the etoposide-induced cells and found that the mitochondrial level of Bax is elevated by more than three fold in etoposide-treated cells and this elevation is effectively prevented in cells expressing Cdk2-dn under the same conditions. Etoposide 50-59 cyclin dependent kinase 2 Homo sapiens 30-34 17252195-6 2007 We screened for mitochondrial Cdk2 targets in the etoposide-induced cells and found that the mitochondrial level of Bax is elevated by more than three fold in etoposide-treated cells and this elevation is effectively prevented in cells expressing Cdk2-dn under the same conditions. Etoposide 50-59 cyclin dependent kinase 2 Homo sapiens 247-251 17252195-6 2007 We screened for mitochondrial Cdk2 targets in the etoposide-induced cells and found that the mitochondrial level of Bax is elevated by more than three fold in etoposide-treated cells and this elevation is effectively prevented in cells expressing Cdk2-dn under the same conditions. Etoposide 159-168 cyclin dependent kinase 2 Homo sapiens 30-34 17252195-6 2007 We screened for mitochondrial Cdk2 targets in the etoposide-induced cells and found that the mitochondrial level of Bax is elevated by more than three fold in etoposide-treated cells and this elevation is effectively prevented in cells expressing Cdk2-dn under the same conditions. Etoposide 159-168 cyclin dependent kinase 2 Homo sapiens 247-251 17389612-4 2007 In the studies examining changes in cell cycle and apoptosis regulators, isosilybin B and isosilybin A resulted in a decrease in the levels of both cyclins (D1, D3, E and A) and cyclin-dependent kinases (Cdk2, Cdk4 and cell division cycle 25A), but caused an increase in p21, p27 and p53 levels, except in 22Rv1 cells where isosilybin B caused a decrease in p21 protein level. isosilybin A 90-102 cyclin dependent kinase 2 Homo sapiens 204-208 17414622-7 2007 LY293111 reduced the expression of CDK2, cyclin A and cyclin E, consistent with the S-phase arrest observed in these cells. LY 293111 0-8 cyclin dependent kinase 2 Homo sapiens 35-39 17335939-0 2007 3D-QSAR and molecular docking study on bisarylmaleimide series as glycogen synthase kinase 3, cyclin dependent kinase 2 and cyclin dependent kinase 4 inhibitors: an insight into the criteria for selectivity. bisarylmaleimide 39-55 cyclin dependent kinase 2 Homo sapiens 94-119 17335939-3 2007 Initially, sets of three individual CoMFA models were developed, using 36 compounds of bisarylmaleimide series to correlate with the GSK3, CDK2 and CDK4 inhibitory potencies. bisarylmaleimide 87-103 cyclin dependent kinase 2 Homo sapiens 139-143 17530771-5 2007 Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showed that propolin H has inhibited CDK2 and CDK4 kinase activities. propolin H 195-205 cyclin dependent kinase 2 Homo sapiens 79-104 17530771-5 2007 Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showed that propolin H has inhibited CDK2 and CDK4 kinase activities. propolin H 195-205 cyclin dependent kinase 2 Homo sapiens 106-110 17530771-5 2007 Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showed that propolin H has inhibited CDK2 and CDK4 kinase activities. propolin H 195-205 cyclin dependent kinase 2 Homo sapiens 154-158 17530771-5 2007 Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showed that propolin H has inhibited CDK2 and CDK4 kinase activities. propolin H 195-205 cyclin dependent kinase 2 Homo sapiens 220-224 17530771-6 2007 Accordingly, coimmunoprecipitations revealed an increased association of both CDK2 and CDK4 immunoreactive protein with the p21Waf1/Cip1 protein complex under propolin H-treated conditions. propolin H 159-169 cyclin dependent kinase 2 Homo sapiens 78-82 17213809-7 2007 The distinct genes that are selectively modulated by dasatinib are cyclin-dependent kinase 2 (CDK2) and CDK8, which had a maximal reduction of <5-fold in microarray screen. Dasatinib 53-62 cyclin dependent kinase 2 Homo sapiens 67-92 17213809-7 2007 The distinct genes that are selectively modulated by dasatinib are cyclin-dependent kinase 2 (CDK2) and CDK8, which had a maximal reduction of <5-fold in microarray screen. Dasatinib 53-62 cyclin dependent kinase 2 Homo sapiens 94-98 17213809-9 2007 K562 and TF-1BCR-ABL cells, pretreated with CDK2 or CDK8 small interfering RNA, showed additive growth inhibition with imatinib, but not with dasatinib. Imatinib Mesylate 119-127 cyclin dependent kinase 2 Homo sapiens 44-48 17213809-10 2007 These findings demonstrate that the additive/synergistic growth inhibition by imatinib and dasatinib may be mediated in part by CDK2 and CDK8. Imatinib Mesylate 78-86 cyclin dependent kinase 2 Homo sapiens 128-132 17213809-10 2007 These findings demonstrate that the additive/synergistic growth inhibition by imatinib and dasatinib may be mediated in part by CDK2 and CDK8. Dasatinib 91-100 cyclin dependent kinase 2 Homo sapiens 128-132 17414622-10 2007 LY293111 also induces S-phase arrest with downregulation of CDK2, cyclin A and cyclin E. Blockade of leukotriene B4 metabolic pathway may provide a novel treatment for human pancreatic cancer. LY 293111 0-8 cyclin dependent kinase 2 Homo sapiens 60-64 17545545-6 2007 Mifepristone blocked DNA synthesis, arrested the cell cycle at the G(1)-S transition, up-regulated cyclin-dependent kinase (cdk) inhibitors p21(cip1)and p27(kip1), down-regulated transcription factor E2F1, decreased expression of the E2F1-regulated genes cdk1 (cdc2) and cyclin A, and modestly decreased cdk2 and cyclin E levels. Mifepristone 0-12 cyclin dependent kinase 2 Homo sapiens 304-308 17343830-4 2007 Analysis of cell cycle proteins revealed that the major difference between the cell lines was that in HCT116, 17-AAG resulted in profound inhibition of expression and phosphorylation of late G1 proteins cyclin E and cdk2, with no effect on p21/WAF1 induction. tanespimycin 110-116 cyclin dependent kinase 2 Homo sapiens 216-220 17343830-7 2007 Inhibition of G1/S progression using cdk2 inhibitor also enhanced oxaliplatin cytotoxicity. Oxaliplatin 66-77 cyclin dependent kinase 2 Homo sapiens 37-41 17450625-0 2007 6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors. 6-substituted pyrrolo[3,4-c]pyrazoles 0-37 cyclin dependent kinase 2 Homo sapiens 60-64 17450625-1 2007 We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. bicyclic tetrahydropyrrolo[3,4-c]pyrazole 77-118 cyclin dependent kinase 2 Homo sapiens 41-45 17545545-7 2007 The abrupt arrest in cell growth induced by mifepristone correlated with reduced cdk2 activity, increased association of cdk2 with p21(cip1) and p27(kip1), increased nuclear localization of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In vivo, mifepristone significantly delayed the growth of ovarian carcinoma xenografts in a dose-dependent manner and without apparent toxic effects for the animals. Mifepristone 44-56 cyclin dependent kinase 2 Homo sapiens 81-85 17545545-7 2007 The abrupt arrest in cell growth induced by mifepristone correlated with reduced cdk2 activity, increased association of cdk2 with p21(cip1) and p27(kip1), increased nuclear localization of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In vivo, mifepristone significantly delayed the growth of ovarian carcinoma xenografts in a dose-dependent manner and without apparent toxic effects for the animals. Mifepristone 44-56 cyclin dependent kinase 2 Homo sapiens 121-125 17545545-7 2007 The abrupt arrest in cell growth induced by mifepristone correlated with reduced cdk2 activity, increased association of cdk2 with p21(cip1) and p27(kip1), increased nuclear localization of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In vivo, mifepristone significantly delayed the growth of ovarian carcinoma xenografts in a dose-dependent manner and without apparent toxic effects for the animals. Mifepristone 44-56 cyclin dependent kinase 2 Homo sapiens 121-125 17545545-9 2007 Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21(cip1) and p27(kip1) and reduced nuclear cdk2/cyclin E complex availability. Mifepristone 0-12 cyclin dependent kinase 2 Homo sapiens 30-34 17545545-9 2007 Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21(cip1) and p27(kip1) and reduced nuclear cdk2/cyclin E complex availability. Mifepristone 0-12 cyclin dependent kinase 2 Homo sapiens 83-87 17545545-9 2007 Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21(cip1) and p27(kip1) and reduced nuclear cdk2/cyclin E complex availability. Mifepristone 0-12 cyclin dependent kinase 2 Homo sapiens 83-87 17571187-0 2007 Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinase 2. 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine 26-85 cyclin dependent kinase 2 Homo sapiens 100-125 17222494-7 2007 The kinase activities of cyclin-dependent kinase 2 (CDK2) and CDK4 were suppressed in MEC-treated cells. Meclizine 86-89 cyclin dependent kinase 2 Homo sapiens 25-50 17222494-7 2007 The kinase activities of cyclin-dependent kinase 2 (CDK2) and CDK4 were suppressed in MEC-treated cells. Meclizine 86-89 cyclin dependent kinase 2 Homo sapiens 52-56 17571187-1 2007 An efficient synthesis of 2-substituted O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines from 6-amino-2-mercaptopyrimidin-4-ol has been developed and used to prepare a range of derivatives for evaluation as inhibitors of cyclin-dependent kinase 2 (CDK2). 2-substituted o(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines 26-90 cyclin dependent kinase 2 Homo sapiens 223-248 17571187-1 2007 An efficient synthesis of 2-substituted O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines from 6-amino-2-mercaptopyrimidin-4-ol has been developed and used to prepare a range of derivatives for evaluation as inhibitors of cyclin-dependent kinase 2 (CDK2). 2-substituted o(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines 26-90 cyclin dependent kinase 2 Homo sapiens 250-254 17571187-1 2007 An efficient synthesis of 2-substituted O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines from 6-amino-2-mercaptopyrimidin-4-ol has been developed and used to prepare a range of derivatives for evaluation as inhibitors of cyclin-dependent kinase 2 (CDK2). 6-amino-2-thiouracil 96-128 cyclin dependent kinase 2 Homo sapiens 223-248 17571187-1 2007 An efficient synthesis of 2-substituted O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines from 6-amino-2-mercaptopyrimidin-4-ol has been developed and used to prepare a range of derivatives for evaluation as inhibitors of cyclin-dependent kinase 2 (CDK2). 6-amino-2-thiouracil 96-128 cyclin dependent kinase 2 Homo sapiens 250-254 17437483-3 2007 GSP-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest at 24 h, which was mediated through the inhibition of cyclin-dependent kinases (Cdk) Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and simultaneous increase in protein expression of cyclin-dependent kinase inhibitors (Cdki), Cip1/p21 and Kip1/p27, and enhanced binding of Cdki-Cdk. Grape Seed Proanthocyanidins 0-3 cyclin dependent kinase 2 Homo sapiens 181-185 17096381-5 2007 It is further demonstrated that p27 was phosphorylated on threonine 187 during S phase progression by Cdk2 and that phosphorylated p27 was polyubiquitylated and degraded. Threonine 58-67 cyclin dependent kinase 2 Homo sapiens 102-106 17217918-5 2007 In vitro kinase assay revealed that amlodipine significantly decreased CDK2-, CDK4-, and their partners cyclin E- and cyclin D1-associated kinase activities. Amlodipine 36-46 cyclin dependent kinase 2 Homo sapiens 71-75 17217918-6 2007 The amlodipine-induced reductions in cyclin D1 protein expression and in CDK2 kinase activity were reproduced by a dihydropyridine derivative, nicardipine, having an inhibitory effect on A431 cell growth, but not by nifedipine, lacking the antiproliferative activity. Amlodipine 4-14 cyclin dependent kinase 2 Homo sapiens 73-77 17217918-6 2007 The amlodipine-induced reductions in cyclin D1 protein expression and in CDK2 kinase activity were reproduced by a dihydropyridine derivative, nicardipine, having an inhibitory effect on A431 cell growth, but not by nifedipine, lacking the antiproliferative activity. 1,4-dihydropyridine 115-130 cyclin dependent kinase 2 Homo sapiens 73-77 17217918-6 2007 The amlodipine-induced reductions in cyclin D1 protein expression and in CDK2 kinase activity were reproduced by a dihydropyridine derivative, nicardipine, having an inhibitory effect on A431 cell growth, but not by nifedipine, lacking the antiproliferative activity. Nicardipine 143-154 cyclin dependent kinase 2 Homo sapiens 73-77 17361108-2 2007 The trimeric complex CDK7/cyclin H/Mat1 phosphorylates the cell cycle regulated cyclin-dependent kinase, CDK2 at Thr-160 in the activation segment in vitro. Threonine 113-116 cyclin dependent kinase 2 Homo sapiens 105-109 17361108-4 2007 Here we show that monomeric human CDK2 purified from bacteria is phosphorylated at Thr-160. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 34-38 17361108-6 2007 The kinase activity was dependent on both the catalytic activity of CDK2 and Thr-160 phosphorylation since it was abolished when CDK2 was mutated at Lys33 in the ATP binding site (K33R) or Thr160 (T160A) or when treated with lambda phosphatase. Threonine 77-80 cyclin dependent kinase 2 Homo sapiens 68-72 17361108-6 2007 The kinase activity was dependent on both the catalytic activity of CDK2 and Thr-160 phosphorylation since it was abolished when CDK2 was mutated at Lys33 in the ATP binding site (K33R) or Thr160 (T160A) or when treated with lambda phosphatase. Threonine 77-80 cyclin dependent kinase 2 Homo sapiens 129-133 17361108-6 2007 The kinase activity was dependent on both the catalytic activity of CDK2 and Thr-160 phosphorylation since it was abolished when CDK2 was mutated at Lys33 in the ATP binding site (K33R) or Thr160 (T160A) or when treated with lambda phosphatase. Adenosine Triphosphate 162-165 cyclin dependent kinase 2 Homo sapiens 68-72 17361108-6 2007 The kinase activity was dependent on both the catalytic activity of CDK2 and Thr-160 phosphorylation since it was abolished when CDK2 was mutated at Lys33 in the ATP binding site (K33R) or Thr160 (T160A) or when treated with lambda phosphatase. Adenosine Triphosphate 162-165 cyclin dependent kinase 2 Homo sapiens 129-133 17361108-8 2007 Consistent with a role of CDK2 in auto-activation, inhibition of CDK2 in human cells either by pharmacological inhibition of CDK2 or by the coexpression of the CDK2 inhibitors p21 or p27, inhibited CDK2 Thr-160 phosphorylation. Threonine 203-206 cyclin dependent kinase 2 Homo sapiens 65-69 17361108-8 2007 Consistent with a role of CDK2 in auto-activation, inhibition of CDK2 in human cells either by pharmacological inhibition of CDK2 or by the coexpression of the CDK2 inhibitors p21 or p27, inhibited CDK2 Thr-160 phosphorylation. Threonine 203-206 cyclin dependent kinase 2 Homo sapiens 65-69 17361108-8 2007 Consistent with a role of CDK2 in auto-activation, inhibition of CDK2 in human cells either by pharmacological inhibition of CDK2 or by the coexpression of the CDK2 inhibitors p21 or p27, inhibited CDK2 Thr-160 phosphorylation. Threonine 203-206 cyclin dependent kinase 2 Homo sapiens 65-69 17361108-8 2007 Consistent with a role of CDK2 in auto-activation, inhibition of CDK2 in human cells either by pharmacological inhibition of CDK2 or by the coexpression of the CDK2 inhibitors p21 or p27, inhibited CDK2 Thr-160 phosphorylation. Threonine 203-206 cyclin dependent kinase 2 Homo sapiens 65-69 17056669-4 2007 In addition, 2-ME treatment upregulates the expression of cyclin-dependent kinase 2 (Cdk2). 2-Methoxyestradiol 13-17 cyclin dependent kinase 2 Homo sapiens 58-83 17431115-7 2007 Thus, Apo2L/TRAIL + CPT-11 treatment-induced apoptosis is regulated through an S-phase checkpoint controlled by the Chk2-Cdc25A and Chk1-Cdc25A pathways and inhibition of Cdk2-associated kinase activity. Irinotecan 20-26 cyclin dependent kinase 2 Homo sapiens 171-175 17056669-4 2007 In addition, 2-ME treatment upregulates the expression of cyclin-dependent kinase 2 (Cdk2). 2-Methoxyestradiol 13-17 cyclin dependent kinase 2 Homo sapiens 85-89 17056669-5 2007 The present study was designed to characterize endoreduplication of human SMCs and explore the potential roles of Cdk2 in endoreduplication induced by 2-ME. 2-Methoxyestradiol 151-155 cyclin dependent kinase 2 Homo sapiens 114-118 17056669-7 2007 Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. 2-Methoxyestradiol 13-17 cyclin dependent kinase 2 Homo sapiens 51-55 17056669-7 2007 Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. 2-Methoxyestradiol 13-17 cyclin dependent kinase 2 Homo sapiens 137-141 17056669-7 2007 Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. 2-Methoxyestradiol 249-253 cyclin dependent kinase 2 Homo sapiens 51-55 17056669-7 2007 Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. 2-Methoxyestradiol 249-253 cyclin dependent kinase 2 Homo sapiens 137-141 17056669-8 2007 We conclude that 2-ME induces endoreduplication of human SMCs and Cdk2 plays an important role in endoreduplication in response to 2-ME. 2-Methoxyestradiol 131-135 cyclin dependent kinase 2 Homo sapiens 66-70 17178224-2 2007 Isothiazolidine 1,1-dioxide analogues showed potent CDK1 and CDK2 inhibitory activities and inhibited proliferation of EJ, HCT116, SW620, and MDAMB468 cancer cells. isothiazolidine 1,1-dioxide 0-27 cyclin dependent kinase 2 Homo sapiens 61-65 17138864-8 2007 Immunoprecipitation studies demonstrated increased association of both p21(Cip1) and p27(Kip1) with Cdk2 as well as diminished Cdk2 kinase activity after isoprenoid exposure, indicating a cell cycle-inhibitory role for p21(Cip1) and p27(Kip1) in pancreatic adenocarcinoma cells. Terpenes 154-164 cyclin dependent kinase 2 Homo sapiens 127-131 17273780-6 2007 The iberin-induced cell cycle arrest in neuroblastoma cells was associated with inhibition of expression of Cdk2, Cdk4, and Cdk6 proteins. iberin 4-10 cyclin dependent kinase 2 Homo sapiens 108-112 17203463-2 2007 We reported recently that roscovitine (ROSC), a potent cyclin-dependent kinase 2 inhibitor, arrests human MCF-7 breast cancer cells in the G(2) phase of the cell cycle and concomitantly induces apoptosis. Roscovitine 26-37 cyclin dependent kinase 2 Homo sapiens 55-80 17203463-2 2007 We reported recently that roscovitine (ROSC), a potent cyclin-dependent kinase 2 inhibitor, arrests human MCF-7 breast cancer cells in the G(2) phase of the cell cycle and concomitantly induces apoptosis. Roscovitine 39-43 cyclin dependent kinase 2 Homo sapiens 55-80 17004068-6 2007 The dbcAMP (0.5 mM) treatment increased CDK2 activity, and it significantly decreased p27Kip1 expression with a decreased half-life of p27Kip1 protein. Bucladesine 4-10 cyclin dependent kinase 2 Homo sapiens 40-44 17125805-9 2007 Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Roscovitine 36-47 cyclin dependent kinase 2 Homo sapiens 120-124 17095507-0 2007 How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A. Tyrosine 4-12 cyclin dependent kinase 2 Homo sapiens 57-82 17095507-3 2007 Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate binding and through the creation of an environment that favors a non-productive conformation of the terminal group of ATP. Adenosine Triphosphate 275-278 cyclin dependent kinase 2 Homo sapiens 41-45 17095507-4 2007 By contrast, tyrosine phosphorylation of CDK2 alters neither its Km for ATP nor its significant intrinsic ATPase activity. Tyrosine 13-21 cyclin dependent kinase 2 Homo sapiens 41-45 17095507-4 2007 By contrast, tyrosine phosphorylation of CDK2 alters neither its Km for ATP nor its significant intrinsic ATPase activity. Adenosine Triphosphate 72-75 cyclin dependent kinase 2 Homo sapiens 41-45 17095507-5 2007 Tyr-15-phosphorylated CDK2 retains trace protein phosphorylation activity that should be considered in quantitative and qualitative cell cycle models. Tyrosine 0-3 cyclin dependent kinase 2 Homo sapiens 22-26 17283158-7 2007 We further show that nelfinavir inhibits CDK2 through proteasome-dependent degradation of Cdc25A phosphatase. Nelfinavir 21-31 cyclin dependent kinase 2 Homo sapiens 41-45 17004068-8 2007 CONCLUSIONS: cAMP up-regulates Skp2 protein by reducing its degradation probably through decreasing the ubiquitination of Skp2, which might result in accelerated degradation of p27Kip1, increase in CDK2 activity, and stimulation of SH-SY5Y cell proliferation in sequence. Cyclic AMP 13-17 cyclin dependent kinase 2 Homo sapiens 198-202 17404016-1 2007 Roscovitine (ROSC), a potent cyclin-dependent kinase inhibitor (CDI), inactivates cyclin-dependent kinase (CDK)2 resulting in the arrest of human MCF-7 breast cancer cells in G2 phase of the cell cycle. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 107-112 17224799-9 2007 Finally, causal relationships between ADAR1 and Cdk2 were confirmed by a study with the Cdk2 inhibitor, kenpaullone, which prevented the ADAR1-induced shift from the G0-G1 to the S phase. kenpaullone 104-115 cyclin dependent kinase 2 Homo sapiens 48-52 17224799-9 2007 Finally, causal relationships between ADAR1 and Cdk2 were confirmed by a study with the Cdk2 inhibitor, kenpaullone, which prevented the ADAR1-induced shift from the G0-G1 to the S phase. kenpaullone 104-115 cyclin dependent kinase 2 Homo sapiens 88-92 17223702-3 2007 The rate constant for dissociation is slow compared to the rate constant for phosphate transfer to form the phospho-enzyme intermediate (k2 = 1.1 s(-1)), making Cdk2-pTpY/CycA a sticky substrate. Phosphates 77-86 cyclin dependent kinase 2 Homo sapiens 161-165 17123821-0 2007 Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. alvocidib 88-100 cyclin dependent kinase 2 Homo sapiens 45-49 17123821-4 2007 Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol. alvocidib 170-182 cyclin dependent kinase 2 Homo sapiens 118-122 17108053-6 2007 The vPK physically associated with and strongly phosphorylated K-bZIP at threonine 111, a site also recognized by the cyclin-dependent kinase Cdk2. Threonine 73-82 cyclin dependent kinase 2 Homo sapiens 142-146 17064874-4 2007 Analysis of the cell cycle regulatory proteins demonstrated that THDB did not change the steady-state levels of cyclin B1, cyclin E, Cdk1 and Cdc25C, but decreased the protein levels of Cdk2 and cyclin A. (Z)-2-(6-(thieanisyl-2-yl)hexa-3-en-1,5-diynyl)benzenamine 65-69 cyclin dependent kinase 2 Homo sapiens 186-190 17254966-5 2007 Instead, it causes phosphorylated Y88 and the entire inhibitory 3(10)-helix of p27 to be ejected from the Cdk2 active site, thus restoring partial Cdk activity. y88 34-37 cyclin dependent kinase 2 Homo sapiens 106-110 17254966-6 2007 Importantly, this allows Y88-phosphorylated p27 to be efficiently phosphorylated on threonine 187 by Cdk2 which in turn promotes its SCF-Skp2-dependent degradation. y88 25-28 cyclin dependent kinase 2 Homo sapiens 101-105 17254966-6 2007 Importantly, this allows Y88-phosphorylated p27 to be efficiently phosphorylated on threonine 187 by Cdk2 which in turn promotes its SCF-Skp2-dependent degradation. Threonine 84-93 cyclin dependent kinase 2 Homo sapiens 101-105 17085505-1 2007 We report a combined quantum mechanics/molecular mechanics (QM/MM) study to determine the protein-ligand interaction energy between CDK2 (cyclin-dependent kinase 2) and five inhibitors with the N(2)-substituted 6-cyclohexyl-methoxy-purine scaffold. n(2)-substituted 6-cyclohexyl-methoxy-purine 194-238 cyclin dependent kinase 2 Homo sapiens 132-136 17085505-1 2007 We report a combined quantum mechanics/molecular mechanics (QM/MM) study to determine the protein-ligand interaction energy between CDK2 (cyclin-dependent kinase 2) and five inhibitors with the N(2)-substituted 6-cyclohexyl-methoxy-purine scaffold. n(2)-substituted 6-cyclohexyl-methoxy-purine 194-238 cyclin dependent kinase 2 Homo sapiens 138-163 17404016-1 2007 Roscovitine (ROSC), a potent cyclin-dependent kinase inhibitor (CDI), inactivates cyclin-dependent kinase (CDK)2 resulting in the arrest of human MCF-7 breast cancer cells in G2 phase of the cell cycle. Roscovitine 13-17 cyclin dependent kinase 2 Homo sapiens 107-112 16920736-5 2007 We further found that PFE treatment also resulted in (i) induction of WAF1/p21 and KIP1/p27, (ii) decrease in the protein expressions of cyclins D1, D2 and E, and (iii) decrease in cyclin-dependent kinase (cdk) 2, cdk4 and cdk6 expression. Coconut Oil 22-25 cyclin dependent kinase 2 Homo sapiens 181-212 17131463-1 2007 X-ray structures from CDK2-aminopyrimidine inhibitor complexes led to the idea to stabilize the active conformation of aminopyrimidine inhibitors by incorporating the recognition site into a macrocyclic framework. 2-aminopyrimidine 27-42 cyclin dependent kinase 2 Homo sapiens 22-26 17131463-1 2007 X-ray structures from CDK2-aminopyrimidine inhibitor complexes led to the idea to stabilize the active conformation of aminopyrimidine inhibitors by incorporating the recognition site into a macrocyclic framework. 2-aminopyrimidine 119-134 cyclin dependent kinase 2 Homo sapiens 22-26 17031514-5 2007 We evaluated growth-inhibitory activity of flavanone and 2"-OH flavanone against highly proliferative human lung cancer cells (A549) via anchorage-independent and -dependent colony formation assay, and further showed that treatment of flavanone resulted in a G1 cell cycle arrest with reduction of cyclin D, E and cyclin-dependent kinase (CDK) 2, while treatment of 2"-OH flavanone led to a G2/M phase accumulation with reduction of cyclin B, D and Cdc2. flavanone 43-52 cyclin dependent kinase 2 Homo sapiens 314-345 17636466-1 2007 A cyclin-dependent kinase, Cdk2, catalyzes the transfer of the gamma-phosphate from ATP to a threonine or serine residue of its polypeptide substrates. gamma-phosphate 63-78 cyclin dependent kinase 2 Homo sapiens 27-31 17636466-1 2007 A cyclin-dependent kinase, Cdk2, catalyzes the transfer of the gamma-phosphate from ATP to a threonine or serine residue of its polypeptide substrates. Adenosine Triphosphate 84-87 cyclin dependent kinase 2 Homo sapiens 27-31 17636466-1 2007 A cyclin-dependent kinase, Cdk2, catalyzes the transfer of the gamma-phosphate from ATP to a threonine or serine residue of its polypeptide substrates. Threonine 93-102 cyclin dependent kinase 2 Homo sapiens 27-31 17636466-1 2007 A cyclin-dependent kinase, Cdk2, catalyzes the transfer of the gamma-phosphate from ATP to a threonine or serine residue of its polypeptide substrates. Serine 106-112 cyclin dependent kinase 2 Homo sapiens 27-31 17161815-4 2007 PD98059 also decreased the Cdk-2, Cdk-4, cyclin D1, and cyclin E expression, and increased high levels of the mitotic inhibitors p16(INIa), p21(Waf1), and p27(Kip1). 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 0-7 cyclin dependent kinase 2 Homo sapiens 27-32 17325859-3 2007 Seliciclib (CYC202, R-roscovitine) is a purine analog developed as an inhibitor of CDK2/cyclin E CDK7/cyclin H and CDK9/cyclin T. Seliciclib has been shown to be active in B-cell neoplasms, such as mantle cell lymphoma, chronic lymphocytic leukemia and in multiple myeloma in vitro. Roscovitine 12-18 cyclin dependent kinase 2 Homo sapiens 83-87 16770643-1 2007 Molecular dynamics simulations were performed to elucidate the interactions of CDK2 and CDK5 complexes with three inhibitors: R-roscovitine, S-roscovitine, and indirubin-3"-oxime. Roscovitine 126-139 cyclin dependent kinase 2 Homo sapiens 79-83 16770643-1 2007 Molecular dynamics simulations were performed to elucidate the interactions of CDK2 and CDK5 complexes with three inhibitors: R-roscovitine, S-roscovitine, and indirubin-3"-oxime. Roscovitine 141-154 cyclin dependent kinase 2 Homo sapiens 79-83 16770643-1 2007 Molecular dynamics simulations were performed to elucidate the interactions of CDK2 and CDK5 complexes with three inhibitors: R-roscovitine, S-roscovitine, and indirubin-3"-oxime. indirubin-3'-monoxime 160-178 cyclin dependent kinase 2 Homo sapiens 79-83 16770643-4 2007 The simulations also showed two amino acid mutations in the active site of CDK5/R-roscovitine that favor binding-enhanced electrostatic contributions, making the inhibitor more effective for CDK5 than for CDK2. Roscovitine 82-93 cyclin dependent kinase 2 Homo sapiens 205-209 17266627-0 2007 3D-QSAR CoMFA study on oxindole derivatives as cyclin dependent kinase 1 (CDK1) and cyclin dependent kinase 2 (CDK2) inhibitors. 2-oxindole 23-31 cyclin dependent kinase 2 Homo sapiens 84-109 17325859-3 2007 Seliciclib (CYC202, R-roscovitine) is a purine analog developed as an inhibitor of CDK2/cyclin E CDK7/cyclin H and CDK9/cyclin T. Seliciclib has been shown to be active in B-cell neoplasms, such as mantle cell lymphoma, chronic lymphocytic leukemia and in multiple myeloma in vitro. Roscovitine 20-33 cyclin dependent kinase 2 Homo sapiens 83-87 17266627-0 2007 3D-QSAR CoMFA study on oxindole derivatives as cyclin dependent kinase 1 (CDK1) and cyclin dependent kinase 2 (CDK2) inhibitors. 2-oxindole 23-31 cyclin dependent kinase 2 Homo sapiens 111-115 17266627-2 2007 With the purpose of designing new chemical entities with enhanced inhibitory potencies against cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 1 (CDK1), the 3D-QSAR CoMFA study carried out on oxindole derivatives as inhibitors of these kinases is presented here. 2-oxindole 205-213 cyclin dependent kinase 2 Homo sapiens 95-120 17266627-2 2007 With the purpose of designing new chemical entities with enhanced inhibitory potencies against cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 1 (CDK1), the 3D-QSAR CoMFA study carried out on oxindole derivatives as inhibitors of these kinases is presented here. 2-oxindole 205-213 cyclin dependent kinase 2 Homo sapiens 122-126 17206862-6 2007 Broad inhibition of cell cycle-regulated kinases (Cdk1/Cdk2/Cdk5/Cdk9) with indirubin-3"-monoxime substantially decreases viral yields and synergizes with the viral UL97 kinase inhibitor, maribavir. indirubin-3'-monoxime 76-97 cyclin dependent kinase 2 Homo sapiens 55-59 17927510-3 2007 In the G1-phase related proteins, hesperetin downregulates the cyclin-dependent kinases (CDKs) and cyclins and upregulates p21(Cip1) and p27(Kip1) in cells treated with hesperetin for 48 h and 72 h. After 72 h treatment, these phenomenons were more pronounced. hesperetin 34-44 cyclin dependent kinase 2 Homo sapiens 89-93 17927510-4 2007 Hesperetin treatment at high concentration for 72 h resulted in a decrease in CDK2 and CDK4 together with cyclin D. In addition, hesperetin increases the binding of CDK4 with p21(Cip1) but not p27(Kip1) or p57(Kip2). hesperetin 0-10 cyclin dependent kinase 2 Homo sapiens 78-82 17927510-4 2007 Hesperetin treatment at high concentration for 72 h resulted in a decrease in CDK2 and CDK4 together with cyclin D. In addition, hesperetin increases the binding of CDK4 with p21(Cip1) but not p27(Kip1) or p57(Kip2). hesperetin 129-139 cyclin dependent kinase 2 Homo sapiens 78-82 17206862-6 2007 Broad inhibition of cell cycle-regulated kinases (Cdk1/Cdk2/Cdk5/Cdk9) with indirubin-3"-monoxime substantially decreases viral yields and synergizes with the viral UL97 kinase inhibitor, maribavir. maribavir 188-197 cyclin dependent kinase 2 Homo sapiens 55-59 17015463-3 2006 Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. Threonine 24-27 cyclin dependent kinase 2 Homo sapiens 63-67 17088910-0 2006 Upregulation of p27 and its inhibition of CDK2/cyclin E activity following DNA damage by a novel platinum agent are dependent on the expression of p21. Platinum 97-105 cyclin dependent kinase 2 Homo sapiens 42-46 17088910-3 2006 We have now evaluated the role of another CDK inhibitor p27 as a contributor to DAP-mediated inhibition of G1-phase CDK2 activity. (diaminocyclohexane)(diacetato)(dichloro)platinum 80-83 cyclin dependent kinase 2 Homo sapiens 116-120 17088910-6 2006 Moreover, DAP-induced p21 promoted the selective increase of p27 in the CDK2 complex, but not in CDK4 complex, and this selective increase contributed to inhibition of the CDK2 kinase activity. (diaminocyclohexane)(diacetato)(dichloro)platinum 10-13 cyclin dependent kinase 2 Homo sapiens 72-76 17088910-6 2006 Moreover, DAP-induced p21 promoted the selective increase of p27 in the CDK2 complex, but not in CDK4 complex, and this selective increase contributed to inhibition of the CDK2 kinase activity. (diaminocyclohexane)(diacetato)(dichloro)platinum 10-13 cyclin dependent kinase 2 Homo sapiens 172-176 17065226-7 2006 Interestingly, coincident with the accumulation of cells in the S/G2/M phase and histone H1 phosphorylation, E1A was relocated to the cytoplasm at the late stage of the viral cycle, which was blocked by the CDC2/CDK2 inhibitor roscovitine. Roscovitine 227-238 cyclin dependent kinase 2 Homo sapiens 212-216 17015463-3 2006 Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. Threonine 24-27 cyclin dependent kinase 2 Homo sapiens 36-61 17119452-11 2006 The increased expressions of p53 and p21, and the decreased expressions of cyclin A, cyclin E, CDK2 and CDK4, indicated the cell cycle arrest at G1/S phase after the cells had been treated with sodium ascorbate. Ascorbic Acid 194-210 cyclin dependent kinase 2 Homo sapiens 95-99 17015463-3 2006 Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. Threonine 180-183 cyclin dependent kinase 2 Homo sapiens 36-61 17015463-3 2006 Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. Threonine 180-183 cyclin dependent kinase 2 Homo sapiens 63-67 16930563-11 2006 Consequently, inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2 and Cdk4 were induced. Tyrosine 25-33 cyclin dependent kinase 2 Homo sapiens 81-85 17125257-4 2006 A computational approach employing fold recognition techniques revealed structural similarity to the cellular kinase Cdk2 with a high level of conservation of the functionally important residues in ATP binding sites and the catalytic centers. Adenosine Triphosphate 198-201 cyclin dependent kinase 2 Homo sapiens 117-121 17055492-0 2006 Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells. anandamide 0-10 cyclin dependent kinase 2 Homo sapiens 20-24 17055492-2 2006 We show that a metabolically stable analogue of anandamide, Met-F-AEA, induces an S phase growth arrest correlated with Chk1 activation, Cdc25A degradation and suppression of Cdk2 activity. anandamide 48-58 cyclin dependent kinase 2 Homo sapiens 175-179 16890327-0 2006 3D-QSAR CoMFA study on indenopyrazole derivatives as cyclin dependent kinase 4 (CDK4) and cyclin dependent kinase 2 (CDK2) inhibitors. indenopyrazole 23-37 cyclin dependent kinase 2 Homo sapiens 90-115 17064068-0 2006 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. 4-arylazo-3,5-diamino-1h-pyrazole 0-33 cyclin dependent kinase 2 Homo sapiens 95-99 17064068-1 2006 In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. 4-arylazo-3,5-diamino-1h-pyrazoles 88-122 cyclin dependent kinase 2 Homo sapiens 189-193 17064068-1 2006 In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Adenosine Triphosphate 143-146 cyclin dependent kinase 2 Homo sapiens 189-193 16890327-0 2006 3D-QSAR CoMFA study on indenopyrazole derivatives as cyclin dependent kinase 4 (CDK4) and cyclin dependent kinase 2 (CDK2) inhibitors. indenopyrazole 23-37 cyclin dependent kinase 2 Homo sapiens 117-121 16890327-2 2006 With the objective of designing new chemical entities with enhanced inhibitory potencies against CDK 2 (CDK2) and CDK 4 (CDK4), the 3D-QSAR CoMFA study carried out on indenopyrazole derivatives as inhibitors of these kinases is presented here. indenopyrazole 167-181 cyclin dependent kinase 2 Homo sapiens 97-102 16890327-2 2006 With the objective of designing new chemical entities with enhanced inhibitory potencies against CDK 2 (CDK2) and CDK 4 (CDK4), the 3D-QSAR CoMFA study carried out on indenopyrazole derivatives as inhibitors of these kinases is presented here. indenopyrazole 167-181 cyclin dependent kinase 2 Homo sapiens 104-108 17125195-1 2006 Anilinopyrazoles as CDK2 inhibitors can adopt multiple binding modes depending on the substituents at the 5-position of the pyrazole ring, based on CDK2/cyclin A crystallographic studies. anilinopyrazoles 0-16 cyclin dependent kinase 2 Homo sapiens 20-24 17125195-1 2006 Anilinopyrazoles as CDK2 inhibitors can adopt multiple binding modes depending on the substituents at the 5-position of the pyrazole ring, based on CDK2/cyclin A crystallographic studies. anilinopyrazoles 0-16 cyclin dependent kinase 2 Homo sapiens 148-152 17125195-1 2006 Anilinopyrazoles as CDK2 inhibitors can adopt multiple binding modes depending on the substituents at the 5-position of the pyrazole ring, based on CDK2/cyclin A crystallographic studies. pyrazole 7-15 cyclin dependent kinase 2 Homo sapiens 20-24 17125195-1 2006 Anilinopyrazoles as CDK2 inhibitors can adopt multiple binding modes depending on the substituents at the 5-position of the pyrazole ring, based on CDK2/cyclin A crystallographic studies. pyrazole 7-15 cyclin dependent kinase 2 Homo sapiens 148-152 16621886-4 2006 Our western blot analysis showed that berberine-induced G(1) cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), a simultaneous decrease in Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and enhanced binding of Cdki-Cdk. Berberine 38-47 cyclin dependent kinase 2 Homo sapiens 194-198 17038621-5 2006 CDK2 specifically phosphorylated FOXO1 at serine-249 (Ser249) in vitro and in vivo. Serine 42-48 cyclin dependent kinase 2 Homo sapiens 0-4 16733797-5 2006 Analysis of the cell cycle regulatory proteins demonstrated that THDA did not change the steady-state levels of cyclin B1, cyclin D3 and Cdc25C, but decreased the protein levels of Cdk1, Cdk2 and cyclin A. thda 65-69 cyclin dependent kinase 2 Homo sapiens 187-191 16942782-6 2006 Capsaicin induced G0-G1 phase arrest underwent the promotion of p53 and p21, which is an inhibitor of Cdk2 and cyclin E complex before leading to the inhibitions of both compounds. Capsaicin 0-9 cyclin dependent kinase 2 Homo sapiens 102-106 16806589-0 2006 Exploring QSAR on 3-aminopyrazoles as antitumor agents for their inhibitory activity of CDK2/cyclin A. 3-aminopyrazole 18-34 cyclin dependent kinase 2 Homo sapiens 88-92 16969075-8 2006 As a consequence, it induced inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2 and Cdk4 in Hep3B cells and the cells undergo an arrest in the G1 phase of the cell cycle. Tyrosine 40-48 cyclin dependent kinase 2 Homo sapiens 96-100 17013093-6 2006 Expression of CDK-2 was determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 76 lesions including 41 primary cutaneous melanomas, 15 lymph node melanoma metastases (in eight cases correlated with primary tumours), three melanoma recurrences (two cases correlated with both primary and metastatic melanomas) and 17 nevi. Formaldehyde 60-68 cyclin dependent kinase 2 Homo sapiens 14-19 17003443-14 2006 MG132 caused a significant increase in p21 and p27 protein and decrease in CDK2, but no change in p53, p57, CDK4, or CDK6 protein. benzyloxycarbonylleucyl-leucyl-leucine aldehyde 0-5 cyclin dependent kinase 2 Homo sapiens 75-79 17013093-6 2006 Expression of CDK-2 was determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 76 lesions including 41 primary cutaneous melanomas, 15 lymph node melanoma metastases (in eight cases correlated with primary tumours), three melanoma recurrences (two cases correlated with both primary and metastatic melanomas) and 17 nevi. Paraffin 75-83 cyclin dependent kinase 2 Homo sapiens 14-19 16766008-6 2006 In addition, CAPE enhanced ATRA-induced cell cycle arrest at the G1 phase by decreasing the association of cdk2-cyclin E complex. caffeic acid phenethyl ester 13-17 cyclin dependent kinase 2 Homo sapiens 107-111 17015473-3 2006 Here, we report that phosphorylation of AML1 serines 276 and 303 can be blocked in vivo by inhibitors of the cyclin-dependent kinases (CDKs) Cdk1 and Cdk2. Serine 45-52 cyclin dependent kinase 2 Homo sapiens 150-154 16766008-6 2006 In addition, CAPE enhanced ATRA-induced cell cycle arrest at the G1 phase by decreasing the association of cdk2-cyclin E complex. Tretinoin 27-31 cyclin dependent kinase 2 Homo sapiens 107-111 16936279-7 2006 Here, we report that CDK4 complexes from Nalm-6 extracts phosphorylated in vitro the CDK2-preferred serine 612, which was inhibited by p16INK4a, and fascaplysin. Serine 100-106 cyclin dependent kinase 2 Homo sapiens 85-89 16942020-4 2006 Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4"-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. 6-cyclohexylmethoxy-2-(4"-sulfamoylanilino)purine 47-96 cyclin dependent kinase 2 Homo sapiens 11-36 16942020-4 2006 Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4"-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. NU6102 98-104 cyclin dependent kinase 2 Homo sapiens 11-36 16936279-6 2006 We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Serine 36-43 cyclin dependent kinase 2 Homo sapiens 65-69 16969115-2 2006 Roscovitine arrests cell cycle progression in G(1) and in G(2) phase by inhibiting CDK2 and CDK1, and possibly CDK7 and CDK9. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 83-87 16936279-6 2006 We reasoned that phosphorylation of serines 608/612 by redundant CDKs could accelerate phospho group formation and determined which G1 CDK contributes to serine 612 phosphorylation. Serine 36-42 cyclin dependent kinase 2 Homo sapiens 65-69 16985050-5 2006 Rapamycin causes down-regulation of cyclin D3 protein, retinoblastoma hypophosphorylation, loss of cyclin-dependent kinase (cdk) 4, cdk6, and cdk2 activity. Sirolimus 0-9 cyclin dependent kinase 2 Homo sapiens 142-146 16914540-0 2006 Dependence of cisplatin-induced cell death in vitro and in vivo on cyclin-dependent kinase 2. Cisplatin 14-23 cyclin dependent kinase 2 Homo sapiens 67-92 16914540-5 2006 Herein is reported that cdk2 inhibitory drugs protect kidney cells in vivo and in vitro, that transduction of kidney cells in vitro with dominant-negative cdk2 also protected, and that cdk2 knockout cells were resistant to cisplatin. Cisplatin 223-232 cyclin dependent kinase 2 Homo sapiens 155-159 16914540-5 2006 Herein is reported that cdk2 inhibitory drugs protect kidney cells in vivo and in vitro, that transduction of kidney cells in vitro with dominant-negative cdk2 also protected, and that cdk2 knockout cells were resistant to cisplatin. Cisplatin 223-232 cyclin dependent kinase 2 Homo sapiens 155-159 16914540-6 2006 The cdk2 knockout cells regained cisplatin sensitivity after transduction with wild-type cdk2. Cisplatin 33-42 cyclin dependent kinase 2 Homo sapiens 4-8 16914540-7 2006 It is concluded that cisplatin cytotoxicity depends on cdk2 activation and that the mechanism of p21 protection is by direct inhibition of cdk2. Cisplatin 21-30 cyclin dependent kinase 2 Homo sapiens 55-59 16914540-7 2006 It is concluded that cisplatin cytotoxicity depends on cdk2 activation and that the mechanism of p21 protection is by direct inhibition of cdk2. Cisplatin 21-30 cyclin dependent kinase 2 Homo sapiens 139-143 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Lovastatin 19-29 cyclin dependent kinase 2 Homo sapiens 80-84 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Lovastatin 19-29 cyclin dependent kinase 2 Homo sapiens 244-248 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Fluvastatin 31-42 cyclin dependent kinase 2 Homo sapiens 80-84 16913703-5 2006 The Lys89 residue in the ATP-binding pocket of CDK2 is observed to form temporary hydrogen bonds with the three most potent inhibitors. Adenosine Triphosphate 25-28 cyclin dependent kinase 2 Homo sapiens 47-51 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Fluvastatin 31-42 cyclin dependent kinase 2 Homo sapiens 244-248 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Simvastatin 48-59 cyclin dependent kinase 2 Homo sapiens 80-84 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Simvastatin 48-59 cyclin dependent kinase 2 Homo sapiens 244-248 16913703-5 2006 The Lys89 residue in the ATP-binding pocket of CDK2 is observed to form temporary hydrogen bonds with the three most potent inhibitors. Hydrogen 82-90 cyclin dependent kinase 2 Homo sapiens 47-51 16750360-0 2006 CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation. CA 224 0-5 cyclin dependent kinase 2 Homo sapiens 67-71 16824683-4 2006 Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH-SY5Y cell numbers and thymidine incorporation at 24 h after depolarization, and increased the phosphorylation and expression of retinoblastoma protein (RB), the activity of Cdk2 (without changing the activities of Cdk4 and Cdk6), and the expressions of cyclin A and cyclin E. Single and repeated depolarization (once a day for 6 days) had similar effects on RB, Cdks, and cyclins levels and activities. Potassium Chloride 41-44 cyclin dependent kinase 2 Homo sapiens 255-259 16824683-4 2006 Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH-SY5Y cell numbers and thymidine incorporation at 24 h after depolarization, and increased the phosphorylation and expression of retinoblastoma protein (RB), the activity of Cdk2 (without changing the activities of Cdk4 and Cdk6), and the expressions of cyclin A and cyclin E. Single and repeated depolarization (once a day for 6 days) had similar effects on RB, Cdks, and cyclins levels and activities. Potassium Chloride 41-44 cyclin dependent kinase 2 Homo sapiens 444-448 16794187-4 2006 Consistent with the cell-cycle effects, at a molecular level (Western blots), 2-ME inhibited cyclin D(1) and cyclin B(1) expression; cyclin-dependent kinase (cdk)-1 and cdk-2 activity; and retinoblastoma protein (pRb), extracellular signal-regulated kinase (ERK) 1/2, and Akt phosphorylation. 2-Methoxyestradiol 78-82 cyclin dependent kinase 2 Homo sapiens 169-174 16672643-1 2006 Mechanisms of lethality of the three-substituted indolinone and putatively selective cyclin-dependent kinase (CDK)2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) were examined in human leukemia cells. SU 9516 126-201 cyclin dependent kinase 2 Homo sapiens 110-115 16880741-8 2006 These findings reveal that phosphorylation of threonine-373 by CDK2-cyclin E represent a potentially crucial event in the inactivation of the pRb protein. Threonine 46-55 cyclin dependent kinase 2 Homo sapiens 63-67 16861913-9 2006 As a result, trastuzumab inhibited Rb phosphorylation that associates with CDK2, cyclin E, CDK6, cyclin A, or cyclin D1. Rubidium 35-37 cyclin dependent kinase 2 Homo sapiens 75-79 16733081-5 2006 This effect on RGS2 mRNA was blocked by the cyclin-dependent kinase-2 (cdk2) inhibitors roscovitine and purvalanol. Roscovitine 88-99 cyclin dependent kinase 2 Homo sapiens 44-69 16858664-5 2006 Western blot analysis revealed that nimbolide-mediated G2/M arrest was accompanied by the up-regulation of p21, cyclin D2, Chk2; and down-regulation of cyclin A, cyclin E, Cdk2, Rad17. nimbolide 36-45 cyclin dependent kinase 2 Homo sapiens 172-176 16733081-5 2006 This effect on RGS2 mRNA was blocked by the cyclin-dependent kinase-2 (cdk2) inhibitors roscovitine and purvalanol. Roscovitine 88-99 cyclin dependent kinase 2 Homo sapiens 71-75 16733081-5 2006 This effect on RGS2 mRNA was blocked by the cyclin-dependent kinase-2 (cdk2) inhibitors roscovitine and purvalanol. purvalanol B 104-114 cyclin dependent kinase 2 Homo sapiens 44-69 16733081-5 2006 This effect on RGS2 mRNA was blocked by the cyclin-dependent kinase-2 (cdk2) inhibitors roscovitine and purvalanol. purvalanol B 104-114 cyclin dependent kinase 2 Homo sapiens 71-75 16418299-10 2006 ATP-induced stimulation of thymidine incorporation and increase of CDK-2 and CDK-4 expression were blocked by SB-203580 (a p38 MAPK inhibitor) and PD-98059 (an MEK inhibitor), but not by SP-600125 (a JNK inhibitor). 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 147-155 cyclin dependent kinase 2 Homo sapiens 67-72 16418299-11 2006 In conclusion, ATP stimulates proliferation by increasing intracellular Ca2+ concentration and activating p38, p44/42 MAPKs, and CDKs in PTCs. Adenosine Triphosphate 15-18 cyclin dependent kinase 2 Homo sapiens 129-133 16418299-8 2006 ATP increased expression levels of cyclin-dependent kinase (CDK)-2, CDK-4, and cyclin E, which were blocked by suramin, reactive blue 2, MRS-2179, MRS-2159, and nifedipine. Adenosine Triphosphate 0-3 cyclin dependent kinase 2 Homo sapiens 35-66 16574813-7 2006 Furthermore, the down-regulation of the cyclin E and CDK2 was clearly observed in GM3-treated HCT116 cells, but the down-regulation of cyclin D1 and CDK4 was not. gm3 82-85 cyclin dependent kinase 2 Homo sapiens 53-57 16418299-8 2006 ATP increased expression levels of cyclin-dependent kinase (CDK)-2, CDK-4, and cyclin E, which were blocked by suramin, reactive blue 2, MRS-2179, MRS-2159, and nifedipine. Suramin 111-118 cyclin dependent kinase 2 Homo sapiens 35-66 16418299-8 2006 ATP increased expression levels of cyclin-dependent kinase (CDK)-2, CDK-4, and cyclin E, which were blocked by suramin, reactive blue 2, MRS-2179, MRS-2159, and nifedipine. Cibacron Blue F 3GA 120-135 cyclin dependent kinase 2 Homo sapiens 35-66 16418299-8 2006 ATP increased expression levels of cyclin-dependent kinase (CDK)-2, CDK-4, and cyclin E, which were blocked by suramin, reactive blue 2, MRS-2179, MRS-2159, and nifedipine. Nifedipine 161-171 cyclin dependent kinase 2 Homo sapiens 35-66 16418299-10 2006 ATP-induced stimulation of thymidine incorporation and increase of CDK-2 and CDK-4 expression were blocked by SB-203580 (a p38 MAPK inhibitor) and PD-98059 (an MEK inhibitor), but not by SP-600125 (a JNK inhibitor). Adenosine Triphosphate 0-3 cyclin dependent kinase 2 Homo sapiens 67-72 16418299-10 2006 ATP-induced stimulation of thymidine incorporation and increase of CDK-2 and CDK-4 expression were blocked by SB-203580 (a p38 MAPK inhibitor) and PD-98059 (an MEK inhibitor), but not by SP-600125 (a JNK inhibitor). SB 203580 110-119 cyclin dependent kinase 2 Homo sapiens 67-72 16909847-0 2006 [Molecular dynamics modeling of the substitution of serine for the conservative glycine in the G loop in the yeast cdc28-srm mutant using the crystalline lattice of human kinase CDK2]. Serine 52-58 cyclin dependent kinase 2 Homo sapiens 178-182 16909847-0 2006 [Molecular dynamics modeling of the substitution of serine for the conservative glycine in the G loop in the yeast cdc28-srm mutant using the crystalline lattice of human kinase CDK2]. Glycine 80-87 cyclin dependent kinase 2 Homo sapiens 178-182 16909847-1 2006 Two-nanosecond molecular dynamics modeling of the crystalline lattice of an active complex of kinase pT160-CDK2/cyclin A/ATP-Mg2+ substrate has been performed. Adenosine Triphosphate 121-124 cyclin dependent kinase 2 Homo sapiens 107-111 16909847-1 2006 Two-nanosecond molecular dynamics modeling of the crystalline lattice of an active complex of kinase pT160-CDK2/cyclin A/ATP-Mg2+ substrate has been performed. magnesium ion 125-129 cyclin dependent kinase 2 Homo sapiens 107-111 16574813-4 2006 Results from our current study show that GM3 treatment dramatically increases cyclin-dependent kinase (CDK) inhibitor (CKI) p21(WAF1) expression through the accumulation of p53 protein by the PTEN-mediated inhibition of the PI-3K/AKT/MDM2 survival signaling in HCT116 colon cancer cells. gm3 41-44 cyclin dependent kinase 2 Homo sapiens 103-106 16765349-0 2006 Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced pre-B lymphoma cell apoptosis. Retinoids 69-77 cyclin dependent kinase 2 Homo sapiens 61-65 16765349-7 2006 Data presented here suggest a novel RA-signaling, by which RA-induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis. Tretinoin 36-38 cyclin dependent kinase 2 Homo sapiens 120-124 16765349-7 2006 Data presented here suggest a novel RA-signaling, by which RA-induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis. Tretinoin 36-38 cyclin dependent kinase 2 Homo sapiens 133-137 16616492-0 2006 A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a potent CDK2/cyclin A inhibitor. 3-hydroxy-2-pyrrolidinone 35-60 cyclin dependent kinase 2 Homo sapiens 84-88 16616492-1 2006 The synthesis of the major metabolite of a potent 3-aminopyrazole CDK2/cyclin A inhibitor is presented. 3-aminopyrazole 50-65 cyclin dependent kinase 2 Homo sapiens 66-70 16818510-7 2006 As a result of its action, tyrosine phosphorylation of the cellular Cdc25A substrates Cdk2 and Cdk4 was induced. Tyrosine 27-35 cyclin dependent kinase 2 Homo sapiens 86-90 16759374-4 2006 Recent work on Cdk2/Cdk4 double knockouts has indicated that these two Cdks are required to phosphorylate Rb during late embryogenesis. Rubidium 106-108 cyclin dependent kinase 2 Homo sapiens 15-19 16627785-8 2006 Taken together, these findings reveal CaM-dependent cyclin E/CDK2 activity as a mediator of the known Ca2+ sensitivity of the G1/S transition of VSMC. vsmc 145-149 cyclin dependent kinase 2 Homo sapiens 61-65 16685393-3 2006 While IFN-alpha or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-alpha and celecoxib or curcumin resulted in a significant growth inhibition of A549 cells, which was associated with down-regulation of CDK2, 4, and 6 and up-regulation of p27. Celecoxib 126-135 cyclin dependent kinase 2 Homo sapiens 252-256 16685393-3 2006 While IFN-alpha or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-alpha and celecoxib or curcumin resulted in a significant growth inhibition of A549 cells, which was associated with down-regulation of CDK2, 4, and 6 and up-regulation of p27. Curcumin 139-147 cyclin dependent kinase 2 Homo sapiens 252-256 17054019-4 2006 In this paper, we present simulation results of CDK2 and CDK5 with roscovitine using models with and without their activators (cyclinA and p25). Roscovitine 67-78 cyclin dependent kinase 2 Homo sapiens 48-52 17054019-7 2006 Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5. Roscovitine 35-46 cyclin dependent kinase 2 Homo sapiens 239-243 17054019-7 2006 Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5. Roscovitine 60-71 cyclin dependent kinase 2 Homo sapiens 239-243 17054019-7 2006 Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5. Glutamine 129-138 cyclin dependent kinase 2 Homo sapiens 22-26 17054019-7 2006 Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5. Glutamine 129-138 cyclin dependent kinase 2 Homo sapiens 239-243 16540140-6 2006 16E1--E4 serine 32 was found to be phosphorylated by Cdk2/cyclin A. Serine 9-15 cyclin dependent kinase 2 Homo sapiens 53-57 16669651-3 2006 When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. beta-aminoethylsulfone 7-29 cyclin dependent kinase 2 Homo sapiens 201-205 16575928-0 2006 Interaction energies for the purine inhibitor roscovitine with cyclin-dependent kinase 2: correlated ab initio quantum-chemical, DFT and empirical calculations. purine 29-35 cyclin dependent kinase 2 Homo sapiens 63-88 16575928-0 2006 Interaction energies for the purine inhibitor roscovitine with cyclin-dependent kinase 2: correlated ab initio quantum-chemical, DFT and empirical calculations. Roscovitine 46-57 cyclin dependent kinase 2 Homo sapiens 63-88 16575928-1 2006 The interaction between roscovitine and cyclin-dependent kinase 2 (cdk2) was investigated by performing correlated ab initio quantum-chemical calculations. Roscovitine 24-35 cyclin dependent kinase 2 Homo sapiens 40-65 16575928-1 2006 The interaction between roscovitine and cyclin-dependent kinase 2 (cdk2) was investigated by performing correlated ab initio quantum-chemical calculations. Roscovitine 24-35 cyclin dependent kinase 2 Homo sapiens 67-71 16669651-3 2006 When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. NU2058 101-127 cyclin dependent kinase 2 Homo sapiens 201-205 16669651-5 2006 The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. Hydrogen 110-118 cyclin dependent kinase 2 Homo sapiens 49-53 16337966-5 2006 Only a low dose of bile acid induced the expression of cyclin D1 and CDC25A and showed high Rb phosphorylation and high CDK2 kinase activity. Bile Acids and Salts 19-28 cyclin dependent kinase 2 Homo sapiens 120-124 16827131-3 2006 Capsaicin-induced G0/G1-phase arrest involved the suppression of CDK2 and the cyclin E complex, which are check-point enzymes for cells moving from G0/G1- to S-phase. Capsaicin 0-9 cyclin dependent kinase 2 Homo sapiens 65-69 16596481-2 2006 A novel inhibitor series based on the 2-amino-4-heteroaryl-pyrimidine scaffold was discovered using the LIDAEUS high-throughput docking methodology, and was subsequently optimized for CDK2 potency through information provided by crystallographic complex structures. 2-amino-4-heteroaryl-pyrimidine 38-69 cyclin dependent kinase 2 Homo sapiens 184-188 16770740-4 2006 The levels of CDK2, CDC2, Cyclin A and Cyclin B proteins decreased, while the levels of CDK inhibitors viz., p21 and p27 were found to increase on staurosporine treatment. Staurosporine 147-160 cyclin dependent kinase 2 Homo sapiens 14-18 16770740-5 2006 The mRNA levels of CDK2 and CDC2 genes were also found to decrease on staurosporine treatment. Staurosporine 70-83 cyclin dependent kinase 2 Homo sapiens 19-23 16770740-6 2006 Thus apart from staurosporine"s known direct inhibitory effect on CDK2 and CDC2 activities, staurosporine was found to down-regulate activities of these two kinases by modulating the expression of the kinases themselves as well that of their activating partners (Cyclins) and their inhibitors. Staurosporine 16-29 cyclin dependent kinase 2 Homo sapiens 66-70 16446360-7 2006 Three serine/proline sites were identified for Cdk2 and Cdk1, and a unique site was phosphorylated by CK2. Serine 6-12 cyclin dependent kinase 2 Homo sapiens 47-51 16446360-7 2006 Three serine/proline sites were identified for Cdk2 and Cdk1, and a unique site was phosphorylated by CK2. Proline 13-20 cyclin dependent kinase 2 Homo sapiens 47-51 16581786-4 2006 Mutagenesis studies show that the rapid turnover of MEF in S phase is dependent on the specific phosphorylation of threonine 643 and serine 648 at the C terminus of MEF by cdk2 and on the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex SCF(Skp2), which targets MEF for ubiquitination and proteolysis. Threonine 115-124 cyclin dependent kinase 2 Homo sapiens 172-176 16537916-1 2006 CrkRS is a Cdc2-related protein kinase that contains an arginine- and serine-rich (SR) domain, a characteristic of the SR protein family of splicing factors, and is proposed to be involved in RNA processing. Serine 70-76 cyclin dependent kinase 2 Homo sapiens 11-38 16581786-4 2006 Mutagenesis studies show that the rapid turnover of MEF in S phase is dependent on the specific phosphorylation of threonine 643 and serine 648 at the C terminus of MEF by cdk2 and on the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex SCF(Skp2), which targets MEF for ubiquitination and proteolysis. Serine 133-139 cyclin dependent kinase 2 Homo sapiens 172-176 16374872-9 2006 In particular, the residues relevant for PPI and for phosphate hydrolysis in the CDK2/Cyclin A and Ras/GAP complexes are analyzed. Phosphates 53-62 cyclin dependent kinase 2 Homo sapiens 81-85 16648567-7 2006 Furthermore, down-regulation of CDK2, CDK4, and cyclin D1 was observed in PC3 cells treated with 1,000 nmol/L of MONCPT, whereas overexpression of CDK7, CDK1, and cyclin B1 was seen in PC3 cells treated with 10 and 100 nmol/L of MONCPT. 10-methoxy-9-nitrocamptothecin 113-119 cyclin dependent kinase 2 Homo sapiens 32-36 16648567-7 2006 Furthermore, down-regulation of CDK2, CDK4, and cyclin D1 was observed in PC3 cells treated with 1,000 nmol/L of MONCPT, whereas overexpression of CDK7, CDK1, and cyclin B1 was seen in PC3 cells treated with 10 and 100 nmol/L of MONCPT. 10-methoxy-9-nitrocamptothecin 229-235 cyclin dependent kinase 2 Homo sapiens 32-36 16325401-0 2006 Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. triazolo(1,5-a)pyrimidine 0-26 cyclin dependent kinase 2 Homo sapiens 36-40 16628247-6 2006 Through a detailed case study of cyclin-dependent kinase 2, we also illustrate how the computational methods can be used to provide new understanding of how phosphorylation drives conformational change, why substituting Glu or Asp for a phosphorylated amino acid does not always mimic the effects of phosphorylation, and how a phosphatase can "capture" a phosphorylated amino acid. Glutamic Acid 220-223 cyclin dependent kinase 2 Homo sapiens 33-58 16628247-6 2006 Through a detailed case study of cyclin-dependent kinase 2, we also illustrate how the computational methods can be used to provide new understanding of how phosphorylation drives conformational change, why substituting Glu or Asp for a phosphorylated amino acid does not always mimic the effects of phosphorylation, and how a phosphatase can "capture" a phosphorylated amino acid. Aspartic Acid 227-230 cyclin dependent kinase 2 Homo sapiens 33-58 16293603-2 2006 Activation of Chk1 in response to cytarabine (ara-C) induced an S-phase checkpoint characterized by the inhibition of Cdk2, cell cycle arrest, no change in constitutively active Akt, or low-stress kinase signaling in ML-1 cells. Cytarabine 34-44 cyclin dependent kinase 2 Homo sapiens 118-122 16293603-2 2006 Activation of Chk1 in response to cytarabine (ara-C) induced an S-phase checkpoint characterized by the inhibition of Cdk2, cell cycle arrest, no change in constitutively active Akt, or low-stress kinase signaling in ML-1 cells. Cytarabine 46-51 cyclin dependent kinase 2 Homo sapiens 118-122 16582606-3 2006 In this context, we have identified RIalpha as a novel substrate for the G(1)/S-Cyclin-dependent kinase, CDK2/Cyclin E, and found that RIalpha is specifically phosphorylated at the serine residue. rialpha 36-43 cyclin dependent kinase 2 Homo sapiens 105-109 16582606-3 2006 In this context, we have identified RIalpha as a novel substrate for the G(1)/S-Cyclin-dependent kinase, CDK2/Cyclin E, and found that RIalpha is specifically phosphorylated at the serine residue. Serine 181-187 cyclin dependent kinase 2 Homo sapiens 105-109 16260160-0 2006 Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors. 2-aminothiazole 52-67 cyclin dependent kinase 2 Homo sapiens 68-72 16892371-1 2006 Recently developed hydrogen-bonding and hydrophobic analysis algorithms were used to investigate the interaction properties of the ATP binding sites of CDK2, CDK4, and ERK2. Hydrogen 19-27 cyclin dependent kinase 2 Homo sapiens 152-156 16892371-1 2006 Recently developed hydrogen-bonding and hydrophobic analysis algorithms were used to investigate the interaction properties of the ATP binding sites of CDK2, CDK4, and ERK2. Adenosine Triphosphate 131-134 cyclin dependent kinase 2 Homo sapiens 152-156 16260160-1 2006 N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50=808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. SCHEMBL5835735 0-38 cyclin dependent kinase 2 Homo sapiens 124-128 16374623-0 2006 The effect of a tightly bound water molecule on scaffold diversity in the computer-aided de novo ligand design of CDK2 inhibitors. Water 30-35 cyclin dependent kinase 2 Homo sapiens 114-118 16374623-1 2006 We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. Water 50-55 cyclin dependent kinase 2 Homo sapiens 96-121 16374623-1 2006 We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. Water 50-55 cyclin dependent kinase 2 Homo sapiens 123-127 16374623-2 2006 In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. Water 68-73 cyclin dependent kinase 2 Homo sapiens 229-233 16260160-2 2006 By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). sbdd 124-128 cyclin dependent kinase 2 Homo sapiens 62-66 16260160-2 2006 By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). sbdd 124-128 cyclin dependent kinase 2 Homo sapiens 181-185 16260160-2 2006 By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide 196-254 cyclin dependent kinase 2 Homo sapiens 62-66 16260160-2 2006 By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide 196-254 cyclin dependent kinase 2 Homo sapiens 181-185 16094629-6 2006 This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. Lovastatin 149-159 cyclin dependent kinase 2 Homo sapiens 241-245 16290148-0 2006 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors. 3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles 0-49 cyclin dependent kinase 2 Homo sapiens 66-70 16284058-1 2006 BACKGROUND: 7-Hydroxystaurosporine (UCN-01) inhibits serine-threonine kinases including the Ca2+ and phospholipid-dependent protein kinase C (PKC), CDKs 2, 4, 6, Chk-1 and PDK1. 7-hydroxystaurosporine 12-34 cyclin dependent kinase 2 Homo sapiens 148-160 16112786-6 2006 These data suggested that Epimedin C arrested the proliferation of these cells at G0/G1 phase through inhibition of CDK2 and CDK4 activities via an increased induction of p21(Cip1) and p27(Kip1). epimedin C 26-36 cyclin dependent kinase 2 Homo sapiens 116-120 16289656-4 2006 The peptides are not toxic to cells and target the Cdk2/Cyclin E complex, inhibiting the phosphorylation of serine 5 of RNAPII. Serine 108-114 cyclin dependent kinase 2 Homo sapiens 51-55 16289656-5 2006 Using the Cdk2 X-ray crystallography structure, we found that the low-energy wild-type peptides could bind to the ATP binding pocket, whereas the mutant peptide bound to the Cdk2 interface. Adenosine Triphosphate 114-117 cyclin dependent kinase 2 Homo sapiens 10-14 16452236-11 2006 Taken together, the data suggest that CDK2 activity may play an important event in the IL-1beta-induced COX-2 expression and prostaglandin E(2) synthesis and might represent a novel target for BMS-387032. Dinoprostone 125-143 cyclin dependent kinase 2 Homo sapiens 38-42 16094629-6 2006 This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. Troglitazone 164-176 cyclin dependent kinase 2 Homo sapiens 241-245 16505103-4 2006 The berberine-induced inhibition of proliferation of DU145, PC-3, and LNCaP cells was associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk. Berberine 4-13 cyclin dependent kinase 2 Homo sapiens 214-245 16386795-1 2006 The synthesis, characterization and biological activity of the first zinc(II) complexes with potent inhibitors of cyclin-dependent kinases (CDKs) derived from 6-benzylaminopurine are described. Zinc 69-77 cyclin dependent kinase 2 Homo sapiens 140-144 16386795-1 2006 The synthesis, characterization and biological activity of the first zinc(II) complexes with potent inhibitors of cyclin-dependent kinases (CDKs) derived from 6-benzylaminopurine are described. benzylaminopurine 159-178 cyclin dependent kinase 2 Homo sapiens 140-144 16505103-4 2006 The berberine-induced inhibition of proliferation of DU145, PC-3, and LNCaP cells was associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk. Berberine 4-13 cyclin dependent kinase 2 Homo sapiens 239-242 16505103-4 2006 The berberine-induced inhibition of proliferation of DU145, PC-3, and LNCaP cells was associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk. Berberine 4-13 cyclin dependent kinase 2 Homo sapiens 247-250 16376875-8 2006 These findings indicate the involvement of NPM in the regulation of pre-mRNA processing, and its activity is controlled by CDK2-mediated phosphorylation on Thr(199). Threonine 156-159 cyclin dependent kinase 2 Homo sapiens 123-127 16343435-5 2006 We propose that during TNFalpha-induced apoptosis, PKCdelta-mediated phosphorylation of p21(WAF1/CIP1) at (146)Ser attenuates the Cdk2 binding of p21(WAF1/CIP1) and thereby upregulates Cdk2 activity. Serine 111-114 cyclin dependent kinase 2 Homo sapiens 130-134 16343435-5 2006 We propose that during TNFalpha-induced apoptosis, PKCdelta-mediated phosphorylation of p21(WAF1/CIP1) at (146)Ser attenuates the Cdk2 binding of p21(WAF1/CIP1) and thereby upregulates Cdk2 activity. Serine 111-114 cyclin dependent kinase 2 Homo sapiens 185-189 16376875-3 2006 We have previously identified Thr(199) as the major phosphorylation site of NPM mediated by CDK2/cyclin E (and A), and this phosphorylation is involved in the regulation of centrosome duplication. Threonine 30-33 cyclin dependent kinase 2 Homo sapiens 92-96 16376875-4 2006 In this study, we further examined the effect of CDK2-mediated phosphorylation of NPM by using the antibody that specifically recognizes NPM phosphorylated on Thr(199). Threonine 159-162 cyclin dependent kinase 2 Homo sapiens 49-53 16205645-8 2006 Under this condition, the selenium effect on wild-type p53-activated fragment p21 (p21(WAF)), cyclin-dependent kinase (CDK)1 and CDK2 was also magnified in a manner consistent with enhanced cell growth arrest. Selenium 26-34 cyclin dependent kinase 2 Homo sapiens 129-133 16182537-1 2006 Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, has been known as a CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). indirubin 0-9 cyclin dependent kinase 2 Homo sapiens 201-205 17115080-1 2006 In the present work, we have reviewed data showing that triiodothyronine and its nuclear receptors modify expression of different genes/proteins involved in cell cycle control beginning from growth factors (such as EGF and TGF-beta), to cell surface receptors (EGFR), as well as proteins acting at the cell membrane (Ras), various transcription factors (c-Fos, c-Myc, E2F1), cyclins, Cip/Kip family of cdk2 inhibitors, and p53 inhibitor Mdm2 (Table 1). Triiodothyronine 56-72 cyclin dependent kinase 2 Homo sapiens 402-406 16397259-2 2006 In vitro kinase assays showed that IC50 values for AZ703 against purified cyclin E/cdk2 and cyclin B/cdk1 were 34 and 29 nmol/L, respectively. az703 51-56 cyclin dependent kinase 2 Homo sapiens 83-87 16397259-13 2006 AZ703-induced apoptosis in NCI-H1299 cells was enhanced by small interfering RNA-mediated depletion of cdk9, which caused reduced levels of Mcl-1 and XIAP, suggesting that cdk2, cdk1, and cdk9 represent a rational subset of family members for drug targeting. az703 0-5 cyclin dependent kinase 2 Homo sapiens 172-176 16376875-6 2006 Phosphorylation on Thr(199) by CDK2/cyclin E (and A) targets NPM to nuclear speckles, and enhances the RNA-binding activity of NPM. Threonine 19-22 cyclin dependent kinase 2 Homo sapiens 31-35 16424043-2 2006 A biochemical analysis of human mammary tumor cell lines indicated that rapamycin-induced antiproliferative effects correlated with down-regulation of cellular p21 levels and the levels of p21 in cyclin-dependent kinase (Cdk) 2 and 4 complexes. Sirolimus 72-81 cyclin dependent kinase 2 Homo sapiens 196-233 16182537-1 2006 Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, has been known as a CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Adenosine Triphosphate 134-137 cyclin dependent kinase 2 Homo sapiens 201-205 16426061-6 2006 Compounds from the Available Chemical Directory, along with the known active compounds, were docked into the ATP binding site of CDK2 using the program Glide, and the 650 ligands from the top scored poses were considered for a QRFF-MD analysis. Adenosine Triphosphate 109-112 cyclin dependent kinase 2 Homo sapiens 129-133 16173047-5 2006 8-Chloroadenosine has less effect on the expressions of cyclin-dependent kinase (cdk)2 and cdk4, G(1) phase cyclin-dependent kinases, and only moderately induces the expression of transforming growth factor beta1 (TGFbeta1) and the mitotic inhibitor p27(KIP1). 8-chloroadenosine 0-17 cyclin dependent kinase 2 Homo sapiens 56-86 17237623-6 2006 The vitamin D analogs modulated cell cycle regulators, including decreasing mRNA and protein levels of p21(Waf1/Cip1) (p21) and cyclin-dependent kinase 2 (cdk2), and increasing p27(Kip1) (p27) protein expression. Vitamin D 4-13 cyclin dependent kinase 2 Homo sapiens 128-153 17237623-6 2006 The vitamin D analogs modulated cell cycle regulators, including decreasing mRNA and protein levels of p21(Waf1/Cip1) (p21) and cyclin-dependent kinase 2 (cdk2), and increasing p27(Kip1) (p27) protein expression. Vitamin D 4-13 cyclin dependent kinase 2 Homo sapiens 155-159 16292742-2 2006 In the present study, we have performed a comparative molecular dynamics (MD) study of models of the complex CDK2/Cyclin A/Substrate, which differ for the presence or absence of the phosphate group bound to Thr160. Phosphates 182-191 cyclin dependent kinase 2 Homo sapiens 109-113 16292742-4 2006 In this way, we analyze the influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2 activation loop (AL) and substrate binding in CDK2. pthr160 68-75 cyclin dependent kinase 2 Homo sapiens 104-108 16292742-4 2006 In this way, we analyze the influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2 activation loop (AL) and substrate binding in CDK2. pthr160 68-75 cyclin dependent kinase 2 Homo sapiens 155-159 16292742-4 2006 In this way, we analyze the influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2 activation loop (AL) and substrate binding in CDK2. Aluminum 126-128 cyclin dependent kinase 2 Homo sapiens 104-108 16292742-4 2006 In this way, we analyze the influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2 activation loop (AL) and substrate binding in CDK2. Aluminum 126-128 cyclin dependent kinase 2 Homo sapiens 155-159 16292742-6 2006 Multiple alignments of the CDKs sequences point to the very high conservation of the AL sequence among the CDKs, thus extending our results to all CDKs. Aluminum 85-87 cyclin dependent kinase 2 Homo sapiens 27-31 16292742-6 2006 Multiple alignments of the CDKs sequences point to the very high conservation of the AL sequence among the CDKs, thus extending our results to all CDKs. Aluminum 85-87 cyclin dependent kinase 2 Homo sapiens 107-111 16292742-6 2006 Multiple alignments of the CDKs sequences point to the very high conservation of the AL sequence among the CDKs, thus extending our results to all CDKs. Aluminum 85-87 cyclin dependent kinase 2 Homo sapiens 107-111 16285732-3 2005 Treatment of K562 cells with the Hsp90 inhibitor, geldanamycin, caused a 75% reduction in Cdk2 levels and reduced the levels of its activating kinase, Cdk7, by more than 60%, suggesting that both of these kinases may be Hsp90 clients. geldanamycin 50-62 cyclin dependent kinase 2 Homo sapiens 90-94 16322252-4 2005 We found that DFMO caused a p53-independent increase in p21 and its association with cyclin-dependent kinase (cdk)-2 and decreased cdk-2 protein as well as its phosphorylation on Thr160. Eflornithine 14-18 cyclin dependent kinase 2 Homo sapiens 85-116 16322252-4 2005 We found that DFMO caused a p53-independent increase in p21 and its association with cyclin-dependent kinase (cdk)-2 and decreased cdk-2 protein as well as its phosphorylation on Thr160. Eflornithine 14-18 cyclin dependent kinase 2 Homo sapiens 131-136 16322252-6 2005 Cdk-2 activity was drastically reduced in DFMO-treated breast cancer cells which exhibited a reduction in retinoblastoma (Rb) phosphorylation and protein. Eflornithine 42-46 cyclin dependent kinase 2 Homo sapiens 0-5 16322252-9 2005 Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 36-43 cyclin dependent kinase 2 Homo sapiens 116-121 16322252-9 2005 Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein. U 0126 47-52 cyclin dependent kinase 2 Homo sapiens 116-121 16322252-9 2005 Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein. Eflornithine 65-69 cyclin dependent kinase 2 Homo sapiens 116-121 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 30-37 cyclin dependent kinase 2 Homo sapiens 161-166 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 30-37 cyclin dependent kinase 2 Homo sapiens 201-206 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. U 0126 41-46 cyclin dependent kinase 2 Homo sapiens 161-166 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. U 0126 41-46 cyclin dependent kinase 2 Homo sapiens 201-206 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. Eflornithine 78-82 cyclin dependent kinase 2 Homo sapiens 161-166 16322252-11 2005 MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. Eflornithine 78-82 cyclin dependent kinase 2 Homo sapiens 201-206 16322252-12 2005 As predicted, PD98059 treatment reduced cdk-2 activity and Rb phosphorylation while reversing the decrease in Rb protein induced by DFMO. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 14-21 cyclin dependent kinase 2 Homo sapiens 40-45 16213715-0 2005 Structural basis for the GSK-3beta binding affinity and selectivity against CDK-2 of 1-(4-aminofurazan-3yl)-5-dialkylaminomethyl-1H-[1,2,3] triazole-4-carboxylic acid derivatives. 1-(4-aminofurazan-3yl)-5-dialkylaminomethyl-1h-[1,2,3] triazole-4-carboxylic acid 85-166 cyclin dependent kinase 2 Homo sapiens 76-81 16322307-7 2005 Mechanistic studies revealed that silibinin induces Kip1/p27 but decreases cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)-2, and CDK4 levels in both cell lines. Silybin 34-43 cyclin dependent kinase 2 Homo sapiens 107-138 16322307-9 2005 Furthermore, silibinin strongly inhibited CDK2, CDK4, and CDC2 kinase activity in these HCC cells. Silybin 13-22 cyclin dependent kinase 2 Homo sapiens 42-46 16317137-8 2005 Fisetin decreased the activities of cyclin-dependent kinases (CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P < 0.05). fisetin 0-7 cyclin dependent kinase 2 Homo sapiens 62-67 16285732-4 2005 Using classical pull-down assays and the Hsp90 inhibitory agents geldanamycin and molybdate, Cdk2 is shown to be a genuine client of the Hsp90 chaperone complex. geldanamycin 65-77 cyclin dependent kinase 2 Homo sapiens 93-97 16285732-4 2005 Using classical pull-down assays and the Hsp90 inhibitory agents geldanamycin and molybdate, Cdk2 is shown to be a genuine client of the Hsp90 chaperone complex. molybdate 82-91 cyclin dependent kinase 2 Homo sapiens 93-97 16285732-6 2005 Mutant constructs containing deletions of secondary structural elements from the N- and C-termini of Cdk2 were prepared and assayed for their ability to coadsorb Hsp90 and Cdc37 in a salt-stable high-affinity manner with and without the addition of molybdate. Salts 183-187 cyclin dependent kinase 2 Homo sapiens 101-105 16107892-6 2005 Together with the immunocytochemical analysis at a single cell level that Rb was phosphorylated at serine 612 and threonine 821, sites known to be phosphorylated by CDK2, the data indicated the presence of CDK2 catalytic activity and loss of Rb"s nuclear affinity in ALL cells. Threonine 114-123 cyclin dependent kinase 2 Homo sapiens 206-210 16177568-2 2005 Cables inhibits cdk2 activity by enhancing cdk2 tyrosine 15 phosphorylation by Wee1, which consequently leads to inhibition of cell growth. Tyrosine 48-56 cyclin dependent kinase 2 Homo sapiens 16-20 16177568-2 2005 Cables inhibits cdk2 activity by enhancing cdk2 tyrosine 15 phosphorylation by Wee1, which consequently leads to inhibition of cell growth. Tyrosine 48-56 cyclin dependent kinase 2 Homo sapiens 43-47 15928920-7 2005 Asp86 is a key residue that recognizes NU6102 more effectively with Cdk2 rather than Cdk4. NU6102 39-45 cyclin dependent kinase 2 Homo sapiens 68-72 15928920-9 2005 Energetic analysis reveals that van der Waals interaction and nonpolar contributions to solvent are favorable in the formation of complexes and the sulfonamide group of the ligand plays a crucial role for binding selectivity between Cdk2 and Cdk4. Sulfonamides 148-159 cyclin dependent kinase 2 Homo sapiens 233-237 15931503-0 2005 Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones. indole-2-ones 87-100 cyclin dependent kinase 2 Homo sapiens 38-63 15931503-1 2005 The relationship between the topochemical indices and cyclin-dependent kinase 2 (CDK2) inhibitory activity of indole-2-ones has been investigated. indole-2-ones 110-123 cyclin dependent kinase 2 Homo sapiens 54-79 15931503-1 2005 The relationship between the topochemical indices and cyclin-dependent kinase 2 (CDK2) inhibitory activity of indole-2-ones has been investigated. indole-2-ones 110-123 cyclin dependent kinase 2 Homo sapiens 81-85 16007142-6 2005 Furthermore, the kinase activities of Cdc2 and Cdk2 were significantly decreased following sodium butyrate treatment, accompanying downregulation of cyclin A and cyclin B, as well as upregulation of p21. Butyric Acid 91-106 cyclin dependent kinase 2 Homo sapiens 47-51 16138853-1 2005 Based on the X-ray crystal structure of cAMP-dependent protein kinase (PKA) with the endogenous inhibitor PKI and the X-ray crystal structure of cyclin-dependent kinase 2 (CDK2) with a substrate peptide, a proposal is put forth that some protein kinases bind peptide substrates in their active sites in the poly-L-proline type II (PPII) conformation. Cyclic AMP 40-44 cyclin dependent kinase 2 Homo sapiens 145-170 16138853-1 2005 Based on the X-ray crystal structure of cAMP-dependent protein kinase (PKA) with the endogenous inhibitor PKI and the X-ray crystal structure of cyclin-dependent kinase 2 (CDK2) with a substrate peptide, a proposal is put forth that some protein kinases bind peptide substrates in their active sites in the poly-L-proline type II (PPII) conformation. polyproline 307-321 cyclin dependent kinase 2 Homo sapiens 145-170 16138853-1 2005 Based on the X-ray crystal structure of cAMP-dependent protein kinase (PKA) with the endogenous inhibitor PKI and the X-ray crystal structure of cyclin-dependent kinase 2 (CDK2) with a substrate peptide, a proposal is put forth that some protein kinases bind peptide substrates in their active sites in the poly-L-proline type II (PPII) conformation. polyproline 307-321 cyclin dependent kinase 2 Homo sapiens 172-176 16140252-13 2005 Using the kinase inhibitors BMS-250595, purvalanol B, AG-12275, flavopiridol, and several other compounds, it is demonstrated that one can obtain excellent comparisons between the Kd values of binding to CDK2 obtained by TdCD and ITC. purvalanol B 40-52 cyclin dependent kinase 2 Homo sapiens 204-208 16140252-13 2005 Using the kinase inhibitors BMS-250595, purvalanol B, AG-12275, flavopiridol, and several other compounds, it is demonstrated that one can obtain excellent comparisons between the Kd values of binding to CDK2 obtained by TdCD and ITC. ag-12275 54-62 cyclin dependent kinase 2 Homo sapiens 204-208 16140252-13 2005 Using the kinase inhibitors BMS-250595, purvalanol B, AG-12275, flavopiridol, and several other compounds, it is demonstrated that one can obtain excellent comparisons between the Kd values of binding to CDK2 obtained by TdCD and ITC. alvocidib 64-76 cyclin dependent kinase 2 Homo sapiens 204-208 16036217-0 2005 Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis. Doxorubicin 46-57 cyclin dependent kinase 2 Homo sapiens 9-13 16191191-5 2005 In contrast to Cdk2-cyclin A, which has a well-defined consensus target site ((S/T)PX(K/R)) that strongly favors substrates containing a lysine at the +3 position of substrates, Cdk2-Speedy/Ringo A2 displayed a broad substrate specificity at this position. Lysine 137-143 cyclin dependent kinase 2 Homo sapiens 15-19 16191191-10 2005 Unlike Cdk2-cyclin A, whose activity depends strongly on activating phosphorylation of Cdk2 on Thr-160, neither the overall catalytic activity nor the substrate recognition by Cdk2-Speedy/Ringo A2 was significantly affected by this phosphorylation. Threonine 95-98 cyclin dependent kinase 2 Homo sapiens 87-91 16191191-10 2005 Unlike Cdk2-cyclin A, whose activity depends strongly on activating phosphorylation of Cdk2 on Thr-160, neither the overall catalytic activity nor the substrate recognition by Cdk2-Speedy/Ringo A2 was significantly affected by this phosphorylation. Threonine 95-98 cyclin dependent kinase 2 Homo sapiens 87-91 16081423-9 2005 To confirm that the sequence surrounding serine 1237 was responsible for the differential regulation by Cdk1 and Cdk2, we replaced 4 amino acids flanking the phosphorylation site to mimic a known Cdk2 phosphorylation site present in the Cdc6 protein. Serine 41-47 cyclin dependent kinase 2 Homo sapiens 113-117 16081423-9 2005 To confirm that the sequence surrounding serine 1237 was responsible for the differential regulation by Cdk1 and Cdk2, we replaced 4 amino acids flanking the phosphorylation site to mimic a known Cdk2 phosphorylation site present in the Cdc6 protein. Serine 41-47 cyclin dependent kinase 2 Homo sapiens 196-200 16174846-6 2005 Pol lambda is phosphorylated in vitro by several Cdk/cyclin complexes, including Cdk2/cyclin A, in its proline-serine-rich domain. Proline 103-110 cyclin dependent kinase 2 Homo sapiens 81-85 16174846-6 2005 Pol lambda is phosphorylated in vitro by several Cdk/cyclin complexes, including Cdk2/cyclin A, in its proline-serine-rich domain. Serine 111-117 cyclin dependent kinase 2 Homo sapiens 81-85 16161999-2 2005 The design of the I45DCs was based in part on the structures of trisubstituted purines complexed with cyclin dependent kinase 2 (cdk2), a protein important in regulating the G1/S transition in the cell cycle, and the intramolecular hydrogen bond in I45DCs that predisposes the conformation to one that mimics substituted adenosines. Purines 79-86 cyclin dependent kinase 2 Homo sapiens 102-127 16161999-2 2005 The design of the I45DCs was based in part on the structures of trisubstituted purines complexed with cyclin dependent kinase 2 (cdk2), a protein important in regulating the G1/S transition in the cell cycle, and the intramolecular hydrogen bond in I45DCs that predisposes the conformation to one that mimics substituted adenosines. Purines 79-86 cyclin dependent kinase 2 Homo sapiens 129-133 16161999-2 2005 The design of the I45DCs was based in part on the structures of trisubstituted purines complexed with cyclin dependent kinase 2 (cdk2), a protein important in regulating the G1/S transition in the cell cycle, and the intramolecular hydrogen bond in I45DCs that predisposes the conformation to one that mimics substituted adenosines. Hydrogen 232-240 cyclin dependent kinase 2 Homo sapiens 129-133 16161999-2 2005 The design of the I45DCs was based in part on the structures of trisubstituted purines complexed with cyclin dependent kinase 2 (cdk2), a protein important in regulating the G1/S transition in the cell cycle, and the intramolecular hydrogen bond in I45DCs that predisposes the conformation to one that mimics substituted adenosines. Adenosine 321-331 cyclin dependent kinase 2 Homo sapiens 129-133 16161999-4 2005 The SAR of the I45DCs is consistent with anticipated hydrogen bonding interactions in the ATP-binding site of cdk2. Hydrogen 53-61 cyclin dependent kinase 2 Homo sapiens 110-114 16161999-4 2005 The SAR of the I45DCs is consistent with anticipated hydrogen bonding interactions in the ATP-binding site of cdk2. Adenosine Triphosphate 90-93 cyclin dependent kinase 2 Homo sapiens 110-114 15993080-1 2005 Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. purine 0-6 cyclin dependent kinase 2 Homo sapiens 47-50 15993080-1 2005 Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. Roscovitine 138-149 cyclin dependent kinase 2 Homo sapiens 47-50 15993080-2 2005 In this article, we describe a novel modification of the purine scaffold influencing CDK2 inhibitory activities as well as anticancer properties in cell lines of different histopathological origin. purine 57-63 cyclin dependent kinase 2 Homo sapiens 85-89 15993080-3 2005 The introduced N at position 8 of the purine ring generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3-triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines, whereas the antiproliferative potential of some derivatives remained very high, reflecting their ability to activate p53 tumor suppressor. purine 38-44 cyclin dependent kinase 2 Homo sapiens 68-72 15993080-3 2005 The introduced N at position 8 of the purine ring generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3-triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines, whereas the antiproliferative potential of some derivatives remained very high, reflecting their ability to activate p53 tumor suppressor. triazolopyrimidinone 100-112 cyclin dependent kinase 2 Homo sapiens 68-72 15993080-3 2005 The introduced N at position 8 of the purine ring generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3-triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines, whereas the antiproliferative potential of some derivatives remained very high, reflecting their ability to activate p53 tumor suppressor. 1,2,3-triazolo[4,5-d]pyrimidines 114-146 cyclin dependent kinase 2 Homo sapiens 68-72 15993080-3 2005 The introduced N at position 8 of the purine ring generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3-triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines, whereas the antiproliferative potential of some derivatives remained very high, reflecting their ability to activate p53 tumor suppressor. Purines 105-112 cyclin dependent kinase 2 Homo sapiens 68-72 16036217-6 2005 Our results demonstrate that differential regulation of Cdc2 and Cdk2 activity by different doses of doxorubicin may contribute to the induction of two distinct modes of cell death in hepatoma cells, either apoptosis or cell death through mitotic catastrophe. Doxorubicin 101-112 cyclin dependent kinase 2 Homo sapiens 65-69 16036217-2 2005 In this study, we investigated the role of Cdc2 and Cdk2 kinase in the regulation of the two modes of cell death induced by doxorubicin. Doxorubicin 124-135 cyclin dependent kinase 2 Homo sapiens 52-56 16036217-3 2005 During HD doxorubicin-induced apoptosis, the histone H1-associated activities of Cdc2 and Cdk2 both progressively declined in parallel with reductions in cyclin A and cyclin B protein levels. Doxorubicin 10-21 cyclin dependent kinase 2 Homo sapiens 90-94 16036217-4 2005 In contrast, during LD doxorubicin-induced cell death through mitotic catastrophe, the Cdc2 and Cdk2 kinases were transiently activated 1 day post-treatment, with similar changes seen in the protein levels of cyclin A, cyclin B, and Cdc2. Doxorubicin 23-34 cyclin dependent kinase 2 Homo sapiens 96-100 16036217-5 2005 Treatment with roscovitine, a specific inhibitor of Cdc2 and Cdk2, significantly blocked LD doxorubicin-induced mitotic catastrophe and cell death, but did not affect HD doxorubicin-induced apoptosis in Huh-7, SNU-398, and SNU-449 hepatoma cell lines. Roscovitine 15-26 cyclin dependent kinase 2 Homo sapiens 61-65 15840769-8 2005 Thus the data suggest that the mechanism of p21 protection is by direct inhibition of cdk2 activity and that cisplatin-induced apoptosis is caused by a cdk2-dependent pathway. Cisplatin 109-118 cyclin dependent kinase 2 Homo sapiens 152-156 15975926-4 2005 Altogether, the results show that (R)-roscovitine is rather selective for CDKs, in fact most kinases are not affected. Roscovitine 34-49 cyclin dependent kinase 2 Homo sapiens 74-78 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 18-27 cyclin dependent kinase 2 Homo sapiens 44-48 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 18-27 cyclin dependent kinase 2 Homo sapiens 129-133 16128747-8 2005 After treatment with TPY-835, the activation of Cdk2 was suppressed and phosphorylation of the retinoblastoma (Rb) protein was decreased in SBC-5 cells. tpy 21-24 cyclin dependent kinase 2 Homo sapiens 48-52 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 18-27 cyclin dependent kinase 2 Homo sapiens 129-133 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 44-48 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 129-133 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 129-133 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 44-48 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 129-133 15840769-7 2005 The dependence of cisplatin cytotoxicity on cdk2 activity was also demonstrated because 1) cisplatin caused a marked increase in cdk2 activity, which was prevented by the p21 expression adenovirus, and 2) a cdk2 dominant-negative adenovirus also protected cells from cisplatin-induced apoptosis. Cisplatin 91-100 cyclin dependent kinase 2 Homo sapiens 129-133 16082227-3 2005 We show that CDK2 suppression results in decreased MCM4 phosphorylation at multiple serine and threonine sites. Serine 84-90 cyclin dependent kinase 2 Homo sapiens 13-17 16082227-3 2005 We show that CDK2 suppression results in decreased MCM4 phosphorylation at multiple serine and threonine sites. Threonine 95-104 cyclin dependent kinase 2 Homo sapiens 13-17 16156860-8 2005 Sustained CDK2 catalytic activity, typically associated with megakaryocyte endomitosis, was dramatically decreased in TPA-stimulated Evi1-expressing HEL cells because of significantly reduced levels of cyclin A. Tetradecanoylphorbol Acetate 118-121 cyclin dependent kinase 2 Homo sapiens 10-14 15818598-9 2005 To study the biological significance of cyclin E overexpression in EFT cells, we used flavopiridol, a pan-cyclin-dependent kinase (CDK) inhibitor and found that flavopiridol efficiently suppressed the growth of EFT cells in vitro and in vivo by the inhibition of cyclinE/CDK2 kinase activity and the induction of apoptosis. alvocidib 161-173 cyclin dependent kinase 2 Homo sapiens 271-275 16178778-0 2005 An analysis of the binding modes of ATP-competitive CDK2 inhibitors as revealed by X-ray structures of protein-inhibitor complexes. Adenosine Triphosphate 36-39 cyclin dependent kinase 2 Homo sapiens 52-56 15964852-6 2005 Finally, p21 was phosphorylated by Cdk2 at Ser-130 in vitro, and this ability of Cdk2 to phosphorylate p21 was dependent, in large part, on the presence of cy2. Serine 43-46 cyclin dependent kinase 2 Homo sapiens 35-39 16155345-7 2005 Pretreatment of cells with cdk inhibitor olomoucine impeded cdk2-cyclin E accumulation, but not the induction of p53. olomoucine 41-51 cyclin dependent kinase 2 Homo sapiens 60-64 15964852-5 2005 The ability of wild-type Cdk2 to destabilize p21 required a potential Cdk2 phosphorylation site in p21 at serine 130 and an intact cyclin-binding motif (cy2) in the p21 C terminus. Serine 106-112 cyclin dependent kinase 2 Homo sapiens 25-29 15964852-5 2005 The ability of wild-type Cdk2 to destabilize p21 required a potential Cdk2 phosphorylation site in p21 at serine 130 and an intact cyclin-binding motif (cy2) in the p21 C terminus. Serine 106-112 cyclin dependent kinase 2 Homo sapiens 70-74 15964852-6 2005 Finally, p21 was phosphorylated by Cdk2 at Ser-130 in vitro, and this ability of Cdk2 to phosphorylate p21 was dependent, in large part, on the presence of cy2. Serine 43-46 cyclin dependent kinase 2 Homo sapiens 81-85 15964852-5 2005 The ability of wild-type Cdk2 to destabilize p21 required a potential Cdk2 phosphorylation site in p21 at serine 130 and an intact cyclin-binding motif (cy2) in the p21 C terminus. CY2 153-156 cyclin dependent kinase 2 Homo sapiens 25-29 15964852-6 2005 Finally, p21 was phosphorylated by Cdk2 at Ser-130 in vitro, and this ability of Cdk2 to phosphorylate p21 was dependent, in large part, on the presence of cy2. CY2 156-159 cyclin dependent kinase 2 Homo sapiens 35-39 15964852-6 2005 Finally, p21 was phosphorylated by Cdk2 at Ser-130 in vitro, and this ability of Cdk2 to phosphorylate p21 was dependent, in large part, on the presence of cy2. CY2 156-159 cyclin dependent kinase 2 Homo sapiens 81-85 15851403-4 2005 CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T. MATERIALS AND METHODS: The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. Roscovitine 8-18 cyclin dependent kinase 2 Homo sapiens 116-120 16055707-4 2005 This destruction is triggered by inhibition of CDK2-mediated CDC6 phosphorylation at serine 54. Serine 85-91 cyclin dependent kinase 2 Homo sapiens 47-51 15941859-9 2005 Conversely, CDK2 activity was low and the pRB residues Ser-612 and threonine (Thr)-821, which are exclusively phosphorylated by CDK2 in conjunction with either cyclin E or A, were unphosphorylated in >90% of CD34+ cells. Serine 55-58 cyclin dependent kinase 2 Homo sapiens 128-132 15941859-9 2005 Conversely, CDK2 activity was low and the pRB residues Ser-612 and threonine (Thr)-821, which are exclusively phosphorylated by CDK2 in conjunction with either cyclin E or A, were unphosphorylated in >90% of CD34+ cells. Threonine 78-81 cyclin dependent kinase 2 Homo sapiens 12-16 15941859-9 2005 Conversely, CDK2 activity was low and the pRB residues Ser-612 and threonine (Thr)-821, which are exclusively phosphorylated by CDK2 in conjunction with either cyclin E or A, were unphosphorylated in >90% of CD34+ cells. Threonine 78-81 cyclin dependent kinase 2 Homo sapiens 128-132 15998135-0 2005 The apoptotic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the Cdk2 pathway. epigallocatechin gallate 34-62 cyclin dependent kinase 2 Homo sapiens 102-106 15998135-3 2005 While EGCG was demonstrated to decrease Cdk2 expression and activity and increase caspase-3 activity, overexpression of Cdk2 and treatment with the caspase-3 inhibitor respectively prevented preadipocytes from induction of DNA fragmentation and caspase-3 activity by doses of 100-400 muM of EGCG. epigallocatechin gallate 6-10 cyclin dependent kinase 2 Homo sapiens 40-44 15998135-3 2005 While EGCG was demonstrated to decrease Cdk2 expression and activity and increase caspase-3 activity, overexpression of Cdk2 and treatment with the caspase-3 inhibitor respectively prevented preadipocytes from induction of DNA fragmentation and caspase-3 activity by doses of 100-400 muM of EGCG. epigallocatechin gallate 291-295 cyclin dependent kinase 2 Homo sapiens 120-124 15998135-4 2005 This suggests the Cdk2- and caspase-3-dependent apoptotic effects of EGCG. epigallocatechin gallate 69-73 cyclin dependent kinase 2 Homo sapiens 18-22 15851403-4 2005 CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T. MATERIALS AND METHODS: The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. Roscovitine 20-33 cyclin dependent kinase 2 Homo sapiens 116-120 16020661-3 2005 Here, we examined whether the activity of kinases associated with cyclin A (such as CDK2) is important in determining cellular sensitivity to paclitaxel, a taxane and mitotic inhibitor used in chemotherapy for breast and ovarian cancer. Paclitaxel 142-152 cyclin dependent kinase 2 Homo sapiens 84-88 15763423-2 2005 In this report, we demonstrate that the PPARgamma ligand, ciglitazone, exhibits an anti-proliferative effect and blocks G1/S cell cycle progression through regulation of p27kip1 protein levels and inhibition of Cdk2 activity in HT-29 colon cancer cells. ciglitazone 58-69 cyclin dependent kinase 2 Homo sapiens 211-215 15763423-7 2005 These data suggest that ciglitazone-induced G1/S arrest is through Cdk2 inhibition and an increase of p27kip1 protein levels which in turn is due a balance of ciglitazone"s affect on new protein synthesis and degradation. ciglitazone 24-35 cyclin dependent kinase 2 Homo sapiens 67-71 15856029-8 2005 Kinases assays reveal that cdk1, cdk2 and cdk4 activity are suppressed in AGN193198-treated cells. AGN193198 74-83 cyclin dependent kinase 2 Homo sapiens 33-37 15855168-9 2005 Using phosphopeptide mapping and mutagenesis studies, we found that threonine 29 within the N terminus of Cdt1 is phosphorylated by Cdk2 and required for interaction with Skp2. Threonine 68-77 cyclin dependent kinase 2 Homo sapiens 132-136 16020661-5 2005 Transfection of a dominant-negative (DN)-CDK2 evoked resistance to paclitaxel by preventing cellular progression to mitosis through loss of CDK1 activity. Paclitaxel 67-77 cyclin dependent kinase 2 Homo sapiens 41-45 16020661-6 2005 Reexpression of wild-type CDK2 in DN-CDK2-transfected cancer cells restored CDK2 activity but not paclitaxel sensitivity. Paclitaxel 98-108 cyclin dependent kinase 2 Homo sapiens 26-30 16020661-7 2005 However, expression of cyclin A in DN-CDK2-transfected cells restored their sensitivity to paclitaxel. Paclitaxel 91-101 cyclin dependent kinase 2 Homo sapiens 38-42 16020661-10 2005 Combining taxane chemotherapy with any drug targeting cyclin A-associated kinases (e.g., pure CDK2 inhibitors) should be done with caution, if at all, because of the potential for enhancing taxane resistance. taxane 190-196 cyclin dependent kinase 2 Homo sapiens 94-98 15824106-10 2005 Neuregulin regulated CDK2 activity through coordinating phosphorylation of CDK2 on Thr-160, accumulation of CDK2 in the nucleus, and down-regulation of the CDK2 inhibitory protein p27 in the nucleus. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 21-25 15824106-10 2005 Neuregulin regulated CDK2 activity through coordinating phosphorylation of CDK2 on Thr-160, accumulation of CDK2 in the nucleus, and down-regulation of the CDK2 inhibitory protein p27 in the nucleus. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 75-79 15824106-10 2005 Neuregulin regulated CDK2 activity through coordinating phosphorylation of CDK2 on Thr-160, accumulation of CDK2 in the nucleus, and down-regulation of the CDK2 inhibitory protein p27 in the nucleus. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 75-79 15824106-10 2005 Neuregulin regulated CDK2 activity through coordinating phosphorylation of CDK2 on Thr-160, accumulation of CDK2 in the nucleus, and down-regulation of the CDK2 inhibitory protein p27 in the nucleus. Threonine 83-86 cyclin dependent kinase 2 Homo sapiens 75-79 15949686-7 2005 Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1). beta Carotene 53-66 cyclin dependent kinase 2 Homo sapiens 359-363 15880679-0 2005 Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. BACKGROUND: The mycotoxin, secalonic acid D (SAD), a known animal and potential human cleft palate (CP)-inducing agent, is produced by Pencillium oxalicum in corn. secalonic acid 0-14 cyclin dependent kinase 2 Homo sapiens 93-97 15930768-1 2005 Relationship between topochemical indices and inhibition of CDK2/cyclin A by 3-aminopyrazoles was investigated using a data set comprising of 42 3-aminopyrazoles. 3-aminopyrazole 77-93 cyclin dependent kinase 2 Homo sapiens 60-64 15836613-5 2005 Although GW8510 inhibits CDK2 and other CDKs when tested in in vitro biochemical assays, when used on cultured neurons it only inhibits CDK5, a cytoplasmic CDK that is not associated with cell-cycle progression. GW8510 9-15 cyclin dependent kinase 2 Homo sapiens 25-29 15741163-8 2005 4) Treatment of Caco-2/15 cells with MG132 (a proteasome inhibitor) and (R)-roscovitine (a specific Cdk2 inhibitor) induced an increase in CDX2 protein levels. benzyloxycarbonylleucyl-leucyl-leucine aldehyde 37-42 cyclin dependent kinase 2 Homo sapiens 100-104 15741163-8 2005 4) Treatment of Caco-2/15 cells with MG132 (a proteasome inhibitor) and (R)-roscovitine (a specific Cdk2 inhibitor) induced an increase in CDX2 protein levels. Roscovitine 72-87 cyclin dependent kinase 2 Homo sapiens 100-104 15647388-0 2005 Antimitogenic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways. epigallocatechin gallate 34-62 cyclin dependent kinase 2 Homo sapiens 110-114 15647388-5 2005 Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2. epigallocatechin gallate 6-10 cyclin dependent kinase 2 Homo sapiens 73-77 15647388-5 2005 Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2. epigallocatechin gallate 6-10 cyclin dependent kinase 2 Homo sapiens 113-117 15647388-5 2005 Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2. epigallocatechin gallate 6-10 cyclin dependent kinase 2 Homo sapiens 113-117 15647388-7 2005 Increased phospho-ERK1/2 content and Cdk2 activity, respectively, via the transfection of MEK1 and Cdk2 cDNA into preadipocytes prevented EGCG from reducing cell numbers. epigallocatechin gallate 138-142 cyclin dependent kinase 2 Homo sapiens 37-41 15647388-7 2005 Increased phospho-ERK1/2 content and Cdk2 activity, respectively, via the transfection of MEK1 and Cdk2 cDNA into preadipocytes prevented EGCG from reducing cell numbers. epigallocatechin gallate 138-142 cyclin dependent kinase 2 Homo sapiens 99-103 15647388-8 2005 These data demonstrate the ERK- and Cdk2-dependent antimitogenic effects of EGCG. epigallocatechin gallate 76-80 cyclin dependent kinase 2 Homo sapiens 36-40 15836613-5 2005 Although GW8510 inhibits CDK2 and other CDKs when tested in in vitro biochemical assays, when used on cultured neurons it only inhibits CDK5, a cytoplasmic CDK that is not associated with cell-cycle progression. GW8510 9-15 cyclin dependent kinase 2 Homo sapiens 40-44 15731113-0 2005 Regulation of vascular smooth muscle proliferation by heparin: inhibition of cyclin-dependent kinase 2 activity by p27(kip1). Heparin 54-61 cyclin dependent kinase 2 Homo sapiens 77-102 15713670-7 2005 EGCG inhibited phosphorylation of vimentin at serines 50 and 55 and phosphorylation of vimentin by cyclin-dependent kinase 2 and cAMP-dependent protein kinase. epigallocatechin gallate 0-4 cyclin dependent kinase 2 Homo sapiens 99-124 15731113-5 2005 Our results indicate that the heparin-induced block in G(1) to S phase transition is imposed by p27(kip1)-mediated inhibition of cyclin-dependent kinase 2 activity. Heparin 30-37 cyclin dependent kinase 2 Homo sapiens 129-154 15731113-7 2005 We present evidence that heparin causes stabilization of p27(kip1) protein during G(1) phase and thereby prevents activation of cyclin-dependent kinase 2. Heparin 25-32 cyclin dependent kinase 2 Homo sapiens 128-153 15735718-7 2005 Conversely, inhibition of p21 induction by cycloheximide or by p21 gene deletion prevents DAP-induced inhibition of Cdk4 and Cdk2 activities. dap 90-93 cyclin dependent kinase 2 Homo sapiens 125-129 15609335-11 2005 Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. epigallocatechin gallate 40-44 cyclin dependent kinase 2 Homo sapiens 123-127 15735718-8 2005 Attenuated p53 expression and p21 induction also eliminates DAP-induced G(1)-phase arrest and inhibition of Cdk4 and Cdk2 activities. dap 60-63 cyclin dependent kinase 2 Homo sapiens 117-121 15735718-4 2005 Our previous studies established that treatment of human cancer cells with low effective concentrations of DAP specifically activates the G(1)-phase checkpoint and simultaneously inhibit Cdk4 and Cdk2 activities. dap 107-110 cyclin dependent kinase 2 Homo sapiens 196-200 15735718-9 2005 Together, these findings establish that activation of the p53-p21 pathway is responsible for the DAP-induced G(1)-phase checkpoint response and provide the first solid evidence that p21 induction by p53 during a DNA damage-induced G(1)-phase checkpoint response inhibits both Cdk4 and Cdk2 activities. dap 97-100 cyclin dependent kinase 2 Homo sapiens 285-289 15735718-5 2005 Here we demonstrate that DAP treatment of human cancer cells activates the p53-p21 pathway without activating other known mechanisms that inhibit Cdk4 and Cdk2 activities. dap 25-28 cyclin dependent kinase 2 Homo sapiens 155-159 15708847-5 2005 Additionally, compared with the full-length cyclin E-CDK2 complexes, the LMW cyclin E-CDK2 complexes are significantly more resistant to inhibition by p21 and p27, despite equal binding of the CKIs to the LMW complexes. 2-(4-Amino-N-ethylanilino)ethanol 73-76 cyclin dependent kinase 2 Homo sapiens 53-57 15735718-7 2005 Conversely, inhibition of p21 induction by cycloheximide or by p21 gene deletion prevents DAP-induced inhibition of Cdk4 and Cdk2 activities. Cycloheximide 43-56 cyclin dependent kinase 2 Homo sapiens 125-129 15708847-5 2005 Additionally, compared with the full-length cyclin E-CDK2 complexes, the LMW cyclin E-CDK2 complexes are significantly more resistant to inhibition by p21 and p27, despite equal binding of the CKIs to the LMW complexes. 2-(4-Amino-N-ethylanilino)ethanol 73-76 cyclin dependent kinase 2 Homo sapiens 86-90 15695825-7 2005 We find that the three arginines that anchor phosphothreonine 160 of fully active CDK2 do not contribute equally to structural stabilization. Arginine 23-32 cyclin dependent kinase 2 Homo sapiens 82-86 15833870-0 2005 Phenoxodiol, a novel isoflavone, induces G1 arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21WAF1/CIP1. phenoxodiol 0-11 cyclin dependent kinase 2 Homo sapiens 71-96 15833870-0 2005 Phenoxodiol, a novel isoflavone, induces G1 arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21WAF1/CIP1. Isoflavones 21-31 cyclin dependent kinase 2 Homo sapiens 71-96 15833870-9 2005 In contrast, cellular cdk2 activity obtained from HN12 cell lines exposed to phenoxodiol for 12 hours decreased by 60%, whereas cdk6 activity remained unaltered, suggesting that the loss of cdk2 activity was specific. phenoxodiol 77-88 cyclin dependent kinase 2 Homo sapiens 22-26 15833870-9 2005 In contrast, cellular cdk2 activity obtained from HN12 cell lines exposed to phenoxodiol for 12 hours decreased by 60%, whereas cdk6 activity remained unaltered, suggesting that the loss of cdk2 activity was specific. phenoxodiol 77-88 cyclin dependent kinase 2 Homo sapiens 190-194 15649889-2 2005 Most of the inhibitors identified to date inhibit kinase activity by interfering with the ATP-binding site of CDKs. Adenosine Triphosphate 90-93 cyclin dependent kinase 2 Homo sapiens 110-114 15833870-14 2005 These data therefore indicate that phenoxodiol promotes G(1)-S arrest by the specific loss in cdk2 activity due to p53-independent p21(WAF1) induction. phenoxodiol 35-46 cyclin dependent kinase 2 Homo sapiens 94-98 15695825-7 2005 We find that the three arginines that anchor phosphothreonine 160 of fully active CDK2 do not contribute equally to structural stabilization. Phosphothreonine 45-61 cyclin dependent kinase 2 Homo sapiens 82-86 15868936-6 2005 Ellagic acid also increased p53 and p21 and decreased CDK2 gene expression, that may lead to the G0/G1 arrest of T24 cells. Ellagic Acid 0-12 cyclin dependent kinase 2 Homo sapiens 54-58 15611077-0 2005 Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. indole-3-carbinol 0-17 cyclin dependent kinase 2 Homo sapiens 33-58 15611077-0 2005 Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. indole-3-carbinol 0-17 cyclin dependent kinase 2 Homo sapiens 197-201 15611077-1 2005 Indole-3-carbinol (I3C), a dietary compound found in cruciferous vegetables, induces a robust inhibition of CDK2 specific kinase activity as part of a G1 cell cycle arrest of human breast cancer cells. indole-3-carbinol 0-17 cyclin dependent kinase 2 Homo sapiens 108-112 15713378-0 2005 Benzodipyrazoles: a new class of potent CDK2 inhibitors. benzodipyrazoles 0-16 cyclin dependent kinase 2 Homo sapiens 40-44 15647383-5 2005 The cAMP-induced inhibition of DNA synthesis was associated with the increased binding of p21Cip1 to Cdk2-cyclin complexes, inhibition of Cdk2 kinase activity, dephosphorylation of Rb, and dissociation of PCNA from chromatin in S phase cells. Cyclic AMP 4-8 cyclin dependent kinase 2 Homo sapiens 101-105 15715961-0 2005 CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells. Tretinoin 16-29 cyclin dependent kinase 2 Homo sapiens 0-4 15715961-4 2005 Our findings suggested that the growth inhibition of RA in HCC cells differed according to G(1) phase delay by CDK2 or 4, finally induction of apoptosis. Tretinoin 53-55 cyclin dependent kinase 2 Homo sapiens 111-115 15715961-6 2005 RA treatment caused cell cycle arrest at G(1) and decreased the expressions and activities of CDK2 or CDK4 in RA-sensitive HepG2 and SNU354 cells. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 94-98 15715961-7 2005 On the other hand, RA-resistant Hep3B and SNU449 cells progressed into the S/G(2)+M phase and showed increased CDK2 and CDK4 expression and activity. Tretinoin 19-21 cyclin dependent kinase 2 Homo sapiens 111-115 15715961-8 2005 Since the inhibition of CDK2 or 4 activities resulted in sensitization of HCC cells to RA, the combination of RA and compounds of inhibiting CDKs such as UCN01 and flavopiridol might be a useful targeted therapy strategy for HCC. Tretinoin 87-89 cyclin dependent kinase 2 Homo sapiens 24-28 15647383-5 2005 The cAMP-induced inhibition of DNA synthesis was associated with the increased binding of p21Cip1 to Cdk2-cyclin complexes, inhibition of Cdk2 kinase activity, dephosphorylation of Rb, and dissociation of PCNA from chromatin in S phase cells. Cyclic AMP 4-8 cyclin dependent kinase 2 Homo sapiens 138-142 15689157-8 2005 However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. flavone 51-58 cyclin dependent kinase 2 Homo sapiens 9-13 15608676-7 2005 5-FU confers S-phase arrest through Chk1-mediated Cdc25A proteolysis leading to inhibition of Cdk2. Fluorouracil 0-4 cyclin dependent kinase 2 Homo sapiens 94-98 15686876-1 2005 The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. pyrazolo(1,5-a)pyrimidine 51-77 cyclin dependent kinase 2 Homo sapiens 133-137 15686876-0 2005 Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2. pyrazolo(1,5-a)pyrimidine 27-53 cyclin dependent kinase 2 Homo sapiens 77-102 15686876-1 2005 The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. pyrazolo(1,5-a)pyrimidine 51-77 cyclin dependent kinase 2 Homo sapiens 106-131 15689157-8 2005 However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. Quercetin 78-87 cyclin dependent kinase 2 Homo sapiens 9-13 15689157-8 2005 However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. alvocidib 92-104 cyclin dependent kinase 2 Homo sapiens 9-13 15647840-5 2005 DHT-induced expression of cyclin A and cyclin-dependent kinase 2 (CDK2) protein was also inhibited by co-treatment with BMP-2. Dihydrotestosterone 0-3 cyclin dependent kinase 2 Homo sapiens 39-64 15647840-5 2005 DHT-induced expression of cyclin A and cyclin-dependent kinase 2 (CDK2) protein was also inhibited by co-treatment with BMP-2. Dihydrotestosterone 0-3 cyclin dependent kinase 2 Homo sapiens 66-70 15634006-6 2005 We demonstrate the utility of profile-based analysis of small molecule complexes from the protein-kinase family to identify similarities and differences in binding of ATP, p38, and CDK2 compounds to kinases and how these profiles can be applied to differentiate the selectivity of these inhibitors. Adenosine Triphosphate 167-170 cyclin dependent kinase 2 Homo sapiens 181-185 15561098-3 2005 Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Camptothecin 60-72 cyclin dependent kinase 2 Homo sapiens 231-235 15561098-3 2005 Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Etoposide 74-83 cyclin dependent kinase 2 Homo sapiens 231-235 15561098-3 2005 Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Doxorubicin 88-98 cyclin dependent kinase 2 Homo sapiens 231-235 16075305-0 2005 Understanding and modulating cyclin-dependent kinase inhibitor specificity: molecular modeling and biochemical evaluation of pyrazolopyrimidinones as CDK2/cyclin A and CDK4/cyclin D1 inhibitors. pyrazolopyrimidinones 125-146 cyclin dependent kinase 2 Homo sapiens 150-154 15632290-1 2005 Molecular dynamics (MD) simulations were used to explain structural details of cyclin-dependent kinase-2 (CDK2) inhibition by phosphorylation at T14 and/or Y15 located in the glycine-rich loop (G-loop). Glycine 175-182 cyclin dependent kinase 2 Homo sapiens 79-104 15632290-1 2005 Molecular dynamics (MD) simulations were used to explain structural details of cyclin-dependent kinase-2 (CDK2) inhibition by phosphorylation at T14 and/or Y15 located in the glycine-rich loop (G-loop). Glycine 175-182 cyclin dependent kinase 2 Homo sapiens 106-110 15632290-5 2005 The position of the ATP gamma-phosphate relative to the phosphorylation site (S/T) of the peptide substrate in the active CDK2 is described and compared with inhibited forms of CDK2. atp gamma-phosphate 20-39 cyclin dependent kinase 2 Homo sapiens 122-126 15603961-6 2005 To get a better understanding of the relationship between chemical structure and biological activity, a complex structure of aloisine with GSK-3 was obtained by superimposing GSK-3 into the known cocrystal structure of aloisine-CDK2, and then factors that affect the inhibition activity were investigated further, combining the QSAR study with the complex structure, the results of which are in good accordance and complementary to each other. Aloisine 125-133 cyclin dependent kinase 2 Homo sapiens 228-232 15603961-6 2005 To get a better understanding of the relationship between chemical structure and biological activity, a complex structure of aloisine with GSK-3 was obtained by superimposing GSK-3 into the known cocrystal structure of aloisine-CDK2, and then factors that affect the inhibition activity were investigated further, combining the QSAR study with the complex structure, the results of which are in good accordance and complementary to each other. Aloisine 219-227 cyclin dependent kinase 2 Homo sapiens 228-232 15642221-11 2005 RESULTS: When compared with mismatch sense group, the protein expressions of FAK, JNK and CDK 2 in HPASMCs decreased in antisense-FAK ODNs group and increased in sense-FAK ODNs group significantly. hpasmcs 99-106 cyclin dependent kinase 2 Homo sapiens 90-95 15572662-0 2004 Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Serine 41-47 cyclin dependent kinase 2 Homo sapiens 134-167 15471899-6 2005 of saponins also resulted in a transient accumulation of cells in the S-phase of the cell cycle that was associated with a significant reduction of cyclin-dependant kinase-2 (CDK-2) activity. Saponins 3-11 cyclin dependent kinase 2 Homo sapiens 148-173 15471899-6 2005 of saponins also resulted in a transient accumulation of cells in the S-phase of the cell cycle that was associated with a significant reduction of cyclin-dependant kinase-2 (CDK-2) activity. Saponins 3-11 cyclin dependent kinase 2 Homo sapiens 175-180 15583814-10 2005 After exposure of U937 cultures to resveratrol, the expression of cyclins A and E, as well as that of CDK2 increased, while that of p21CIP was significantly reduced. Resveratrol 35-46 cyclin dependent kinase 2 Homo sapiens 102-106 15604277-6 2004 First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. tetrandrine 7-18 cyclin dependent kinase 2 Homo sapiens 37-62 15604277-6 2004 First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. tetrandrine 7-18 cyclin dependent kinase 2 Homo sapiens 64-68 15607961-4 2004 Expression levels of MITF and CDK2 are tightly correlated in primary melanoma specimens and predict susceptibility to the CDK2 inhibitor roscovitine. Roscovitine 137-148 cyclin dependent kinase 2 Homo sapiens 30-34 15607961-4 2004 Expression levels of MITF and CDK2 are tightly correlated in primary melanoma specimens and predict susceptibility to the CDK2 inhibitor roscovitine. Roscovitine 137-148 cyclin dependent kinase 2 Homo sapiens 122-126 15547725-8 2004 Treatment of HepG2 cells with MEK1/2 inhibitor U0126 resulted in cell cycle arrest, downregulation of cyclin D1 and Cdk-2 expression and inhibition of pRB phosphorylation at Ser780 and Ser795. U 0126 47-52 cyclin dependent kinase 2 Homo sapiens 116-121 15739175-0 2005 Insights from ab initio quantum chemical calculations into the preferred tautomeric forms and binding affinities to CDK2 of substituted pyrazolopyridines. pyrazolopyridine 136-153 cyclin dependent kinase 2 Homo sapiens 116-120 15739175-4 2005 Ab initio free energy calculations were also used to identify determinants of binding affinity for some recently published pyrazolopyridine inhibitors of CDK2. pyrazolopyridine 123-139 cyclin dependent kinase 2 Homo sapiens 154-158 15304523-2 2005 The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. Guanine 52-59 cyclin dependent kinase 2 Homo sapiens 101-105 15304523-5 2005 In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O(6)-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. NU2058 84-92 cyclin dependent kinase 2 Homo sapiens 68-72 15304523-5 2005 In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O(6)-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. Cisplatin 135-144 cyclin dependent kinase 2 Homo sapiens 68-72 16706194-7 2005 The presence of E1A bound p21(Waf1) in cyclin-kinase complexes seems to be the cause of activating phosphorilation of Cdk2 at Thr-160 in cyclin A/E--Cdk2 complexes in both control and X-ray irradiated cells. Threonine 126-129 cyclin dependent kinase 2 Homo sapiens 118-122 16706194-7 2005 The presence of E1A bound p21(Waf1) in cyclin-kinase complexes seems to be the cause of activating phosphorilation of Cdk2 at Thr-160 in cyclin A/E--Cdk2 complexes in both control and X-ray irradiated cells. Threonine 126-129 cyclin dependent kinase 2 Homo sapiens 149-153 15386387-6 2004 In contrast, cells stably expressing H179L-p53 arrested in S-phase following cisplatin treatment, which correlated with a marked decrease in the expression of cdc2, cyclin B1 and cyclin A, and a decrease in CDK2 and cyclin A-associated kinase activity. Cisplatin 77-86 cyclin dependent kinase 2 Homo sapiens 207-211 15505811-4 2004 It is also found that the binding preference of CDK4- selective inhibitors for CDK4 over CDK2 stems from the reduced solvent accessibility in the active site of the former due to the formation of a stable hydrogen-bond triad by the Asp99, Arg101, and Thr102 side chains at the top of the active-site gorge. Hydrogen 205-213 cyclin dependent kinase 2 Homo sapiens 89-93 15505811-5 2004 Besides the differences in loop flexibility and solvent accessibility, the dynamic stabilities of the hydrogen bonds between the inhibitors and the side chain of the lysine residue at the bottom of the active site also correlate well with the relative binding affinities of the inhibitors for the two CDKs. Hydrogen 102-110 cyclin dependent kinase 2 Homo sapiens 301-305 15505811-5 2004 Besides the differences in loop flexibility and solvent accessibility, the dynamic stabilities of the hydrogen bonds between the inhibitors and the side chain of the lysine residue at the bottom of the active site also correlate well with the relative binding affinities of the inhibitors for the two CDKs. Lysine 166-172 cyclin dependent kinase 2 Homo sapiens 301-305 15537345-4 2004 Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. 6-(arylmethyl)pyrazolopyrimidinones 93-128 cyclin dependent kinase 2 Homo sapiens 78-82 15537345-5 2004 Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. Hydrogen 15-23 cyclin dependent kinase 2 Homo sapiens 204-208 15355984-6 2004 The cyclin D1-Cdk2 fusion protein expressed in epithelial cells was phosphorylated on Thr(160) and catalyzed the phosphorylation of Rb on multiple sites in vitro and in vivo. Rubidium 132-134 cyclin dependent kinase 2 Homo sapiens 14-18 15355984-8 2004 Mutational inactivation of the cyclin D1 domain prevented activating phosphorylation of the Cdk2 domain on Thr(160). Threonine 107-110 cyclin dependent kinase 2 Homo sapiens 92-96 15355984-3 2004 This report demonstrates that Cdk2 in cyclin D1-Cdk2 complexes from mammary epithelial cells is phosphorylated on the activating phosphorylation site, Thr(160). Threonine 151-154 cyclin dependent kinase 2 Homo sapiens 30-34 15378019-9 2004 We also found that TAM67 decreased the expression of D and E cyclins, reduced CDK2 and CDK4 activity, and increased the CDK inhibitor p27. tam67 19-24 cyclin dependent kinase 2 Homo sapiens 78-82 15355984-3 2004 This report demonstrates that Cdk2 in cyclin D1-Cdk2 complexes from mammary epithelial cells is phosphorylated on the activating phosphorylation site, Thr(160). Threonine 151-154 cyclin dependent kinase 2 Homo sapiens 48-52 15355984-4 2004 Furthermore, cyclin D1-Cdk2 complexes catalyze Rb phosphorylation on multiple sites in vitro. Rubidium 47-49 cyclin dependent kinase 2 Homo sapiens 23-27 15355984-6 2004 The cyclin D1-Cdk2 fusion protein expressed in epithelial cells was phosphorylated on Thr(160) and catalyzed the phosphorylation of Rb on multiple sites in vitro and in vivo. Threonine 86-89 cyclin dependent kinase 2 Homo sapiens 14-18 15382077-8 2004 The enhanced CQ-dependent loss of functional HER2 from the cell surface resulted in sustained inactivation of the serine/threonine kinase Akt, upregulation of p27Kip1 protein and inhibition of cyclin E/Cdk2 activity. Chloroquine 13-15 cyclin dependent kinase 2 Homo sapiens 202-206 15475007-3 2004 Late in the cell cycle, p27 degradation requires phosphorylation of Thr 187 by cyclin dependent kinase 2, leading to recognition by the SCF ubiquitin ligase containing the Skp2 F-box protein. Threonine 68-71 cyclin dependent kinase 2 Homo sapiens 79-104 15554686-9 2004 In addition, an analysis of the overall results of screening the library against the ATP binding site of two protein targets (HSP90 and CDK2) reveals different patterns of fragment binding, demonstrating that the approach can find selective compounds that discriminate between related binding sites. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 136-140 15474478-2 2004 The structures of CDK2 complexed with roscovitine and deschoroflavopiridol have been reported, however no crystallographic structure is available for complexes of CDK1 with inhibitors. Roscovitine 38-49 cyclin dependent kinase 2 Homo sapiens 18-22 15474478-2 2004 The structures of CDK2 complexed with roscovitine and deschoroflavopiridol have been reported, however no crystallographic structure is available for complexes of CDK1 with inhibitors. deschoroflavopiridol 54-74 cyclin dependent kinase 2 Homo sapiens 18-22 15450939-0 2004 Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. geraniol 0-8 cyclin dependent kinase 2 Homo sapiens 76-101 15450939-0 2004 Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. beta-ionone 13-24 cyclin dependent kinase 2 Homo sapiens 76-101 15450939-2 2004 Mevalonate depletion results in a G1 phase cell cycle arrest that is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and decreased expression of positive regulators of G1 to S phase progression. Mevalonic Acid 0-10 cyclin dependent kinase 2 Homo sapiens 110-141 15450939-8 2004 Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. beta-ionone 5-16 cyclin dependent kinase 2 Homo sapiens 40-45 15450939-8 2004 Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. beta-ionone 5-16 cyclin dependent kinase 2 Homo sapiens 130-141 15450939-8 2004 Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. geraniol 21-29 cyclin dependent kinase 2 Homo sapiens 40-45 15450939-8 2004 Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. geraniol 21-29 cyclin dependent kinase 2 Homo sapiens 130-141 15632311-5 2004 Cyclin A/Cdk2 complexes phosphorylated serine residues on pRb crucial for the G1 to S phase transition in proliferating HepG2 cells, and HGF treatment inhibited the phosphorylation. Serine 39-45 cyclin dependent kinase 2 Homo sapiens 9-13 15327838-4 2004 Further, the PEP8-TAT2 peptide inhibits cell death-associated Cdk2 activity and thereby prevents apoptotic progression in paclitaxel-treated cells. Paclitaxel 122-132 cyclin dependent kinase 2 Homo sapiens 62-66 15309028-8 2004 Like overexpression of p16, fascaplysine induces apoptosis in NP-18 cells, suggesting that inhibition of D-type cyclin/CDK activity in cells with high levels of CycE/CDK2 activity activates an apoptotic pathway. fascaplysine 28-40 cyclin dependent kinase 2 Homo sapiens 166-170 15304301-10 2004 DADS also increased cyclin E and decreased CDK2 gene expression which may lead to the G2/M arrest of T24 cells. diallyl disulfide 0-4 cyclin dependent kinase 2 Homo sapiens 43-47 15350828-4 2004 The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. ursolic acid 24-26 cyclin dependent kinase 2 Homo sapiens 196-200 15517906-7 2004 We speculate that caffeine may enhance MOLT-4 cell entrance into the S-phase through activation of Cdc25, which in turn activates cyclin-dependent protein kinases (CDKs) including CDK2 and drives the cell cycle progression; while degradation of cyclin E by the ubiquitin/proteasome pathway may account for the decreased levels of cyclin E in these cells. Caffeine 18-26 cyclin dependent kinase 2 Homo sapiens 164-168 15247247-12 2004 Furthermore, CTalpha expression is decreased in cells overexpressing a dominant-negative form of CDK2 and in cells treated with the CDK2 kinase inhibitors roscovitine and olomoucine. Roscovitine 155-166 cyclin dependent kinase 2 Homo sapiens 132-136 15247247-12 2004 Furthermore, CTalpha expression is decreased in cells overexpressing a dominant-negative form of CDK2 and in cells treated with the CDK2 kinase inhibitors roscovitine and olomoucine. olomoucine 171-181 cyclin dependent kinase 2 Homo sapiens 132-136 15341487-6 2004 Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. pyrazolo[1,5-b]pyridazin 127-151 cyclin dependent kinase 2 Homo sapiens 55-60 15313404-6 2004 Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. eupatilin 0-9 cyclin dependent kinase 2 Homo sapiens 60-64 15357981-3 2004 A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site. isoindolinone ureas 152-171 cyclin dependent kinase 2 Homo sapiens 9-13 15517906-7 2004 We speculate that caffeine may enhance MOLT-4 cell entrance into the S-phase through activation of Cdc25, which in turn activates cyclin-dependent protein kinases (CDKs) including CDK2 and drives the cell cycle progression; while degradation of cyclin E by the ubiquitin/proteasome pathway may account for the decreased levels of cyclin E in these cells. Caffeine 18-26 cyclin dependent kinase 2 Homo sapiens 180-184 15606011-0 2004 [Effect of ginsenoside Rg1 on expression of p21, cyclin E and CDK2 in the process of cell senescence]. Ginsenosides 11-22 cyclin dependent kinase 2 Homo sapiens 62-66 15308730-4 2004 In contrast, roscovitine and other purine PCIs inhibit with high potency only CDK1, CDK2, CDK5, and CDK7, and they specifically inhibit the expression of viral but not cellular genes. Roscovitine 13-24 cyclin dependent kinase 2 Homo sapiens 84-88 15308730-4 2004 In contrast, roscovitine and other purine PCIs inhibit with high potency only CDK1, CDK2, CDK5, and CDK7, and they specifically inhibit the expression of viral but not cellular genes. purine 35-41 cyclin dependent kinase 2 Homo sapiens 84-88 15342418-7 2004 P21Cip1, cdk1, cdk2, and cyclin E mRNA expression increased coincident with S-phase accumulation in HT29 cells treated with ZD9331 or 5fluorouracil/leucovorin, as demonstrated by cDNA microarray analyses. ZD 9331 124-130 cyclin dependent kinase 2 Homo sapiens 15-19 15342418-7 2004 P21Cip1, cdk1, cdk2, and cyclin E mRNA expression increased coincident with S-phase accumulation in HT29 cells treated with ZD9331 or 5fluorouracil/leucovorin, as demonstrated by cDNA microarray analyses. Fluorouracil 134-147 cyclin dependent kinase 2 Homo sapiens 15-19 15548374-7 2004 An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Phytic Acid 30-33 cyclin dependent kinase 2 Homo sapiens 96-100 15548374-7 2004 An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Phytic Acid 30-33 cyclin dependent kinase 2 Homo sapiens 174-178 15606011-1 2004 AIM: To explore the possible role of p21, cyclin E and cyclin-dependent kinase 2 (CDK2) in the protection of ginsenoside Rg1 against tert-butylhydroperoxide (t-BHP)-induced senescence in WI-38 cells. Ginsenosides 109-120 cyclin dependent kinase 2 Homo sapiens 82-86 15327971-7 2004 In addition, under similar conditions, the expressed level of Cyclin A and CDK-2 in the PC3 cells was significantly reduced after treatment with NAO or its purified components. 10-N-nonylacridinium orange 145-148 cyclin dependent kinase 2 Homo sapiens 75-80 15261277-1 2004 A series of 2-anilino-4-(1H-pyrrol-3-yl)pyrimidines were prepared and evaluated for their ability to inhibit cyclin-dependent kinases (CDKs). 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine 12-51 cyclin dependent kinase 2 Homo sapiens 135-139 15033903-5 2004 The protein and mRNA levels of a CDK inhibitor p21CIP1/WAF1, but not p27KIP1, were markedly increased by saucernetin-7 and p21CIP1/WAF1 induction is likely to occur at the transcriptional level because actinomycin D blocked this induction. saucernetin-7 105-118 cyclin dependent kinase 2 Homo sapiens 33-36 15185342-7 2004 The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Terbinafine 4-6 cyclin dependent kinase 2 Homo sapiens 60-85 15185342-7 2004 The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Terbinafine 4-6 cyclin dependent kinase 2 Homo sapiens 87-91 15155733-0 2004 Mevalonate promotes the growth of tumors derived from human cancer cells in vivo and stimulates proliferation in vitro with enhanced cyclin-dependent kinase-2 activity. Mevalonic Acid 0-10 cyclin dependent kinase 2 Homo sapiens 133-158 15033903-5 2004 The protein and mRNA levels of a CDK inhibitor p21CIP1/WAF1, but not p27KIP1, were markedly increased by saucernetin-7 and p21CIP1/WAF1 induction is likely to occur at the transcriptional level because actinomycin D blocked this induction. Dactinomycin 202-215 cyclin dependent kinase 2 Homo sapiens 33-36 15126498-2 2004 We previously reported that the prostacyclin mimetic, cicaprost, selectively inhibits cyclin E-cyclin-dependent kinase-2 (Cdk2), and now we show that it acts by regulating the expression of Skp2, the F-box protein that targets p27(Kip1) for ubiquitin-mediated proteolysis. Epoprostenol 32-44 cyclin dependent kinase 2 Homo sapiens 122-126 15033903-6 2004 In addition, saucernetin-7 markedly enhanced the binding of p21CIP1/WAF1 with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. saucernetin-7 13-26 cyclin dependent kinase 2 Homo sapiens 78-82 15033903-8 2004 In conclusion, the onset of saucernetin-7-induced the G0/G1 arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the p21CIP1/WAF1 level and a decrease in the CDK2 and CDK6 activities. saucernetin-7 28-41 cyclin dependent kinase 2 Homo sapiens 194-198 15123618-7 2004 In addition, treatment of siRNA-Cdk5 diminished digoxin-triggered cell death, as compared with the treatments of siRNA-Cdk1 or siRNA-Cdk2, which implies the specific involvement of Cdk5 in digoxin-triggered cell death. Digoxin 189-196 cyclin dependent kinase 2 Homo sapiens 133-137 15298730-5 2004 Etodolac induced p21WAF1/Cip1 and p27Kip1 expression and inhibited CDK2, CDK4, CDC2, cyclin A and cyclin B1 expression, but did not affect cyclin D1 or cyclin E. HGF and 10% FBS induced ERK phosphorylation, but phosphorylation of p38, JNK and AKT was down-regulated by etodolac. Etodolac 0-8 cyclin dependent kinase 2 Homo sapiens 67-71 15185335-4 2004 We applied charge optimization to a fragment of the heat-stable protein kinase inhibitor (PKI) of protein kinase A (PKA), to three flavopiridol inhibitors of CDK2, and to cyclin A which interacts with CDK2 to regulate the cell cycle. alvocidib 131-143 cyclin dependent kinase 2 Homo sapiens 158-162 15185335-7 2004 In studying the binding of flavopiridol inhibitors to CDK2, comparable binding affinity could be obtained regardless of whether the net charges of the inhibitors were constrained to -2, -1, 0, 1, or 2 during the optimization. alvocidib 27-39 cyclin dependent kinase 2 Homo sapiens 54-58 15299076-9 2004 Immunoblot analysis showed that sanguinarine treatment of both LNCaP and DU145 cells resulted in significant (1) induction of cyclin kinase inhibitors p21/WAF1 and p27/KIP1; (2) down-regulation of cyclin E, D1, and D2; and (3) down-regulation of cyclin-dependent kinase 2, 4, and 6. sanguinarine 32-44 cyclin dependent kinase 2 Homo sapiens 246-281 15239650-1 2004 The adenosine 5"-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). Adenosine Triphosphate 4-29 cyclin dependent kinase 2 Homo sapiens 318-322 15239650-1 2004 The adenosine 5"-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). Adenosine Triphosphate 31-34 cyclin dependent kinase 2 Homo sapiens 318-322 15239650-1 2004 The adenosine 5"-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). NU2058 82-110 cyclin dependent kinase 2 Homo sapiens 318-322 15239650-1 2004 The adenosine 5"-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). NU2058 112-118 cyclin dependent kinase 2 Homo sapiens 318-322 15126498-2 2004 We previously reported that the prostacyclin mimetic, cicaprost, selectively inhibits cyclin E-cyclin-dependent kinase-2 (Cdk2), and now we show that it acts by regulating the expression of Skp2, the F-box protein that targets p27(Kip1) for ubiquitin-mediated proteolysis. cicaprost 54-63 cyclin dependent kinase 2 Homo sapiens 122-126 15126498-3 2004 First, we show that cicaprost prevents the late G(1) phase down-regulation of p27(Kip1) and that the inhibitory effect of cicaprost on cyclin E-Cdk2 activity and S phase entry is eliminated by deleting p27(Kip1). cicaprost 122-131 cyclin dependent kinase 2 Homo sapiens 144-148 14985333-3 2004 In vivo and in vitro kinase assays with cyclin-CDK2 demonstrate beta-catenin phosphorylation on residues Ser(33), Ser(37), Thr(41), and Ser(45). Serine 105-108 cyclin dependent kinase 2 Homo sapiens 47-51 15252147-2 2004 Although the antiproliferative effect of flavopiridol has been attributed to the inhibition of cyclin-dependent kinases 2 and 4, recent reports indicate that the mechanism responsible for the cell death induced by this agent is more complex. alvocidib 41-53 cyclin dependent kinase 2 Homo sapiens 95-127 15204521-9 2004 Time-course changes of cell cycle regulatory proteins levels revealed accumulation of cyclins A and B as well as of cdc2 and cdk2 upon exposure of IGROV-1 cells to hyperthermia and oxaliplatin. Oxaliplatin 181-192 cyclin dependent kinase 2 Homo sapiens 125-129 15171713-3 2004 Consistent with targeting the G1-S phase transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced progression of G1-arrested cells into S phase and reduced the kinase activities of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3 days. Dihydrotestosterone 53-56 cyclin dependent kinase 2 Homo sapiens 232-236 15122251-3 2004 Regulated turnover of p27 is due, at least partly, to its phosphorylation by Cdk2 on threonine 187, which generates a Skp2-binding site. Threonine 85-94 cyclin dependent kinase 2 Homo sapiens 77-81 15122251-6 2004 Accumulation of p27Luc in response to Cdk2 inhibitory drugs (flavopiridol and R-roscovitine) was demonstrable in human tumor cells in vivo using noninvasive bioluminescent imaging. alvocidib 61-73 cyclin dependent kinase 2 Homo sapiens 38-42 15122251-6 2004 Accumulation of p27Luc in response to Cdk2 inhibitory drugs (flavopiridol and R-roscovitine) was demonstrable in human tumor cells in vivo using noninvasive bioluminescent imaging. Roscovitine 78-91 cyclin dependent kinase 2 Homo sapiens 38-42 15133164-0 2004 Activation and inhibition of cyclin-dependent kinase-2 by phosphorylation; a molecular dynamics study reveals the functional importance of the glycine-rich loop. Glycine 143-150 cyclin dependent kinase 2 Homo sapiens 29-54 15133164-1 2004 Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semiactive CDK2/Cyclin A/ATP, fully active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) were compared. Adenosine Triphosphate 136-139 cyclin dependent kinase 2 Homo sapiens 95-120 15133164-1 2004 Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semiactive CDK2/Cyclin A/ATP, fully active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) were compared. Adenosine Triphosphate 166-169 cyclin dependent kinase 2 Homo sapiens 95-120 15133164-1 2004 Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semiactive CDK2/Cyclin A/ATP, fully active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) were compared. Adenosine Triphosphate 166-169 cyclin dependent kinase 2 Homo sapiens 95-120 15133164-1 2004 Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semiactive CDK2/Cyclin A/ATP, fully active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) were compared. Adenosine Triphosphate 166-169 cyclin dependent kinase 2 Homo sapiens 95-120 15133164-6 2004 The phosphorylated Y15 residue negatively affects substrate binding or its correct alignment for ATP terminal phospho-group transfer to the CDK2 substrate. Adenosine Triphosphate 97-100 cyclin dependent kinase 2 Homo sapiens 140-144 15064732-1 2004 We previously reported that cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y transcription factor and this phosphorylation is essential for DNA binding of NF-Y. Serine 52-58 cyclin dependent kinase 2 Homo sapiens 28-32 15130767-11 2004 In conclusion, these data suggest that BJ-601 inhibits HDMVECs proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally causes retardation of the cell cycle at the G0/G1 phase. 3-amino-2-imino-3,4-dihydro-2H-1,3-benzothiazin-4-one 39-45 cyclin dependent kinase 2 Homo sapiens 140-144 15226429-3 2004 CDK2 inhibition triggers a p53-p21 response via ATM- and ATR-dependent p53 phosphorylation at serine 15. Serine 94-100 cyclin dependent kinase 2 Homo sapiens 0-4 15169628-6 2004 Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chk1 kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. 7-hydroxystaurosporine 150-156 cyclin dependent kinase 2 Homo sapiens 47-51 15136770-6 2004 Treatment of cells with the S-phase blocker PD179483 causes abnormal and persistent hyperactivation of Cdk2 and Cdc2 due to Tyr-15 dephosphorylation. PD179483 44-52 cyclin dependent kinase 2 Homo sapiens 103-107 15136770-6 2004 Treatment of cells with the S-phase blocker PD179483 causes abnormal and persistent hyperactivation of Cdk2 and Cdc2 due to Tyr-15 dephosphorylation. Tyrosine 124-127 cyclin dependent kinase 2 Homo sapiens 103-107 15171713-6 2004 In contrast, DHT treatment caused increased accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations in levels of p27(Kip1) bound to Cdk2 complexes. Dihydrotestosterone 13-16 cyclin dependent kinase 2 Homo sapiens 60-64 15171713-7 2004 These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells. Dihydrotestosterone 28-31 cyclin dependent kinase 2 Homo sapiens 111-115 15171713-7 2004 These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells. Dihydrotestosterone 28-31 cyclin dependent kinase 2 Homo sapiens 185-189 16136956-7 2004 Celecoxib down-regulated the expression of CDK2, CDK4 and up-regulated the expression of P2 WAF1/CIP1 CONCLUSION: The effect of celecoxib inhibiting cell HT-29 proliferation and inducing cell apoptosis may relate to its blocking cell cycle progress. Celecoxib 0-9 cyclin dependent kinase 2 Homo sapiens 43-47 15059135-6 2004 Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. CPG-oligonucleotide 76-100 cyclin dependent kinase 2 Homo sapiens 13-17 15081017-2 2004 Exploration of SAR and optimisation of the imidazo[1,2-a]pyridine CDK inhibitors has lead to the discovery of novel, potent and selective inhibitors of the cyclin-dependent kinase CDK2. imidazo(1,2-a)pyridine 43-65 cyclin dependent kinase 2 Homo sapiens 180-184 14999769-6 2004 We show that GA triggers a rapid and marked decrease in the kinase activity of the cyclin E/cdk2 complex coupled with a decline in both total and cdk2-associated cyclin E. In transient transfection experiments, inhibition of cyclin E expression by GA was correlated with inhibition of the transcriptional activity of the cyclin E gene promoter. Gallium 13-15 cyclin dependent kinase 2 Homo sapiens 92-96 14999769-6 2004 We show that GA triggers a rapid and marked decrease in the kinase activity of the cyclin E/cdk2 complex coupled with a decline in both total and cdk2-associated cyclin E. In transient transfection experiments, inhibition of cyclin E expression by GA was correlated with inhibition of the transcriptional activity of the cyclin E gene promoter. Gallium 13-15 cyclin dependent kinase 2 Homo sapiens 146-150 15141020-9 2004 The camptothecin-induced intra-S checkpoint is partially dependent on ATM, and is associated with inhibitory phosphorylation of cyclin-dependent kinase 2 and reduction of BrdUrd incorporation after mid-S phase. Camptothecin 4-16 cyclin dependent kinase 2 Homo sapiens 128-153 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Water 31-36 cyclin dependent kinase 2 Homo sapiens 108-112 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Water 31-36 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Water 31-36 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Water 31-36 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Adenosine Triphosphate 119-122 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Adenosine Triphosphate 119-122 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Adenosine Triphosphate 119-122 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. N(6)-(delta(2)-isopentenyl)adenine 151-169 cyclin dependent kinase 2 Homo sapiens 108-112 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. N(6)-(delta(2)-isopentenyl)adenine 151-169 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. N(6)-(delta(2)-isopentenyl)adenine 151-169 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-4 2004 Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. N(6)-(delta(2)-isopentenyl)adenine 151-169 cyclin dependent kinase 2 Homo sapiens 114-118 15048820-8 2004 In the CDK2/isopentenyladenine complex simulation, two water molecules that arrange interaction between the inhibitor and the enzyme via an H-bond were observed. N(6)-(delta(2)-isopentenyl)adenine 12-30 cyclin dependent kinase 2 Homo sapiens 7-11 15048820-8 2004 In the CDK2/isopentenyladenine complex simulation, two water molecules that arrange interaction between the inhibitor and the enzyme via an H-bond were observed. Water 55-60 cyclin dependent kinase 2 Homo sapiens 7-11 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). Water 11-16 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). Nitrogen 110-119 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). N(6)-(delta(2)-isopentenyl)adenine 137-155 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). Nitrogen 169-178 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). Adenosine Triphosphate 186-208 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-9 2004 Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). Adenosine Triphosphate 210-213 cyclin dependent kinase 2 Homo sapiens 57-61 15048820-10 2004 The positions of structural water molecules were compared with the positions of substrate polar groups and crystallographic water molecules found in the Brookhaven Protein Data Bank for various CDK2 complexes. Water 124-129 cyclin dependent kinase 2 Homo sapiens 194-198 15047157-2 2004 In the present study, harmine was identified from a collection of herbal compounds to be a specific inhibitor of Cdk1/cyclin B, Cdk2/cyclin A, and Cdk5/p25 with IC50 values at low micromoles. Harmine 22-29 cyclin dependent kinase 2 Homo sapiens 128-132 15059906-7 2004 Histone H1 kinase assays indicated that the delayed entry of RII transfectants into phase was associated with markedly reduced cyclin-dependent kinase (CDK)2 kinase activity. rii 61-64 cyclin dependent kinase 2 Homo sapiens 152-157 14769951-5 2004 Subsequent in vitro binding and activity assays confirmed the protein kinases Ste20-related kinase and cyclin-dependent kinase 2 (CDK2) and the non-protein kinases adenosine kinase and quinone reductase type 2 as novel targets of bisindolylmaleimide inhibitors. bisindolylmaleimide 230-249 cyclin dependent kinase 2 Homo sapiens 103-128 14769951-5 2004 Subsequent in vitro binding and activity assays confirmed the protein kinases Ste20-related kinase and cyclin-dependent kinase 2 (CDK2) and the non-protein kinases adenosine kinase and quinone reductase type 2 as novel targets of bisindolylmaleimide inhibitors. bisindolylmaleimide 230-249 cyclin dependent kinase 2 Homo sapiens 130-134 14769951-6 2004 As observed specifically for CDK2, minor chemical variation of the ligand by immobilizing the closely related bisindolylmaleimides III, VIII, and X dramatically affected target binding. bisindolylmaleimide 110-130 cyclin dependent kinase 2 Homo sapiens 29-33 14767478-6 2004 Cdk2-dn induction could inhibit Cdc25B activity and foster Cdk1 tyr phosphorylation within the S phase, temporally dissociating these events from Cdk1 activation at mitosis. Tyrosine 64-67 cyclin dependent kinase 2 Homo sapiens 0-4 14726525-1 2004 Pentagalloylglucose, which is found in many medicinal plants, can arrest the cell cycle at G(1) phase through down-regulation of cyclin-dependent kinases 2 and 4 and up-regulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(Cip1/WAF1) in human breast cancer cells. pentagalloylglucose 0-19 cyclin dependent kinase 2 Homo sapiens 129-161 15059135-8 2004 Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. Roscovitine 49-60 cyclin dependent kinase 2 Homo sapiens 30-34 15059135-8 2004 Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. Thymidine 71-80 cyclin dependent kinase 2 Homo sapiens 30-34 15059135-10 2004 In addition, inhibition of Cyclin E-cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. Roscovitine 53-64 cyclin dependent kinase 2 Homo sapiens 36-40 15041562-2 2004 METHODS: The expression of CDK-2 gene was examined with reverse transcriptional (RT)-PCR, and the PCR products underwent electrophoresis on non-denaturing poly-acrylamide gel (PAG) followed by silver staining. polyacrylamide gels 176-179 cyclin dependent kinase 2 Homo sapiens 27-32 15123247-5 2004 This knowledge was applied to the design of compounds in the otherwise CDK2-selective 2-anilino-4-(thiazol-5-yl)pyrimidine pharmacophore that are potent and highly selective ATP antagonists of CDK4/cyclin D1. 2-anilino-4-(thiazol-5-yl)pyrimidine 86-122 cyclin dependent kinase 2 Homo sapiens 71-75 15123247-5 2004 This knowledge was applied to the design of compounds in the otherwise CDK2-selective 2-anilino-4-(thiazol-5-yl)pyrimidine pharmacophore that are potent and highly selective ATP antagonists of CDK4/cyclin D1. Adenosine Triphosphate 174-177 cyclin dependent kinase 2 Homo sapiens 71-75 15084985-4 2004 Flow cytometric analysis revealed that pancreatic cancer cells treated with 50 micromol/L LY294002 underwent G1 arrest, which was associated with dephosphorylation of the ppRB protein, a decrease in the protein expression of cyclin D and E, and their activating partners Cdk2, 4, and 6 with simultaneous accumulation of P27/Kip1. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 90-98 cyclin dependent kinase 2 Homo sapiens 271-275 15027857-1 2004 Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines 58-107 cyclin dependent kinase 2 Homo sapiens 143-168 15027857-1 2004 Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines 58-107 cyclin dependent kinase 2 Homo sapiens 170-174 15027857-3 2004 Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. 2-anilino-4-(thiazol-5-yl)pyrimidine 145-181 cyclin dependent kinase 2 Homo sapiens 199-203 15027857-3 2004 Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. 2-anilino-4-(thiazol-5-yl)pyrimidine 145-181 cyclin dependent kinase 2 Homo sapiens 252-256 15027857-3 2004 Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Adenosine Triphosphate 182-185 cyclin dependent kinase 2 Homo sapiens 199-203 15027857-3 2004 Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Adenosine Triphosphate 182-185 cyclin dependent kinase 2 Homo sapiens 252-256 15027863-3 2004 In particular, compound 21 [N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide, BMS-387032], has been identified as an ATP-competitive and CDK2-selective inhibitor which has been selected to enter Phase 1 human clinical trials as an antitumor agent. N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide 28-118 cyclin dependent kinase 2 Homo sapiens 179-183 15041562-2 2004 METHODS: The expression of CDK-2 gene was examined with reverse transcriptional (RT)-PCR, and the PCR products underwent electrophoresis on non-denaturing poly-acrylamide gel (PAG) followed by silver staining. Silver 193-199 cyclin dependent kinase 2 Homo sapiens 27-32 14990704-2 2004 Roscovitine (Rosco) is a purine derivative that inhibits cyclin-dependent kinase 1 (cdk1), cdk2, cdk5, cdk7, and cdk9, which are key regulators of the cell cycle and transcription. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 91-95 14617691-1 2004 Xylocydine (4-amino-6-bromo-7-(beta-l-xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide) blocks cyclin-dependent kinase CDK1 and CDK2/cyclin A activity in vitro (IC(50) 1.4 and 61 nM, respectively) while minimally inhibiting the three other Ser/Thr protein kinases tested (IC(50) 21-86 microM). 4-amino-6-bromo-7-(xylofuranosyl)pyrrolo(2,3-d)pyrimidine-5-carboxamide 0-10 cyclin dependent kinase 2 Homo sapiens 132-136 14617691-1 2004 Xylocydine (4-amino-6-bromo-7-(beta-l-xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide) blocks cyclin-dependent kinase CDK1 and CDK2/cyclin A activity in vitro (IC(50) 1.4 and 61 nM, respectively) while minimally inhibiting the three other Ser/Thr protein kinases tested (IC(50) 21-86 microM). 4-amino-6-bromo-7-(beta-l-xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide 12-90 cyclin dependent kinase 2 Homo sapiens 132-136 14990704-2 2004 Roscovitine (Rosco) is a purine derivative that inhibits cyclin-dependent kinase 1 (cdk1), cdk2, cdk5, cdk7, and cdk9, which are key regulators of the cell cycle and transcription. Roscovitine 0-5 cyclin dependent kinase 2 Homo sapiens 91-95 14990704-2 2004 Roscovitine (Rosco) is a purine derivative that inhibits cyclin-dependent kinase 1 (cdk1), cdk2, cdk5, cdk7, and cdk9, which are key regulators of the cell cycle and transcription. purine 25-31 cyclin dependent kinase 2 Homo sapiens 91-95 14667929-7 2004 Immunoprecipitation showed that the formations of the CDK2-p21 and CDK4-p21 complex, but not the CDK2-p27 and CDK4-p27 complex, were increased in the DPTH-treated HUVEC. diphenylthiohydantoin 150-154 cyclin dependent kinase 2 Homo sapiens 54-58 15026556-0 2004 Cassette dosing pharmacokinetics of a library of 2,6,9-trisubstituted purine cyclin-dependent kinase 2 inhibitors prepared by parallel synthesis. 2,6,9-trisubstituted 49-69 cyclin dependent kinase 2 Homo sapiens 77-102 15026556-3 2004 Here we describe the cassette dosing properties of a 107-membered library of 2,6,9-trisubstituted purine cyclin-dependent kinase 2 (CDK2) inhibitors. 2,6,9-trisubstituted 77-97 cyclin dependent kinase 2 Homo sapiens 105-130 15026556-3 2004 Here we describe the cassette dosing properties of a 107-membered library of 2,6,9-trisubstituted purine cyclin-dependent kinase 2 (CDK2) inhibitors. 2,6,9-trisubstituted 77-97 cyclin dependent kinase 2 Homo sapiens 132-136 15012993-0 2004 A new series of potent oxindole inhibitors of CDK2. 2-oxindole 23-31 cyclin dependent kinase 2 Homo sapiens 46-50 15012993-1 2004 A novel series of oxindole-type inhibitors of CDK2 that have heteroatom substituted alkynyl moieties at their C-4 position is described. 2-oxindole 18-26 cyclin dependent kinase 2 Homo sapiens 46-50 14602088-3 2004 Roscovitine (10 microM), an antitumoral drug that inhibits cyclin-dependent kinase 1 (cdk1), cdk2 and cdk5, showed a significant neuroprotective effect on CGNs deprived of S/K. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 93-97 14761195-3 2004 Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. indirubin 42-52 cyclin dependent kinase 2 Homo sapiens 69-73 14761195-3 2004 Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. Adenosine Triphosphate 141-144 cyclin dependent kinase 2 Homo sapiens 69-73 14597612-1 2004 The cyclin-dependent kinase (CDK)-activating kinase (CAK) phosphorylates a conserved threonine residue on CDKs and activates them. Threonine 85-94 cyclin dependent kinase 2 Homo sapiens 106-110 14597612-5 2004 p42 is essential for the phosphorylation of Thr-160 and activation of CDK2. Threonine 44-47 cyclin dependent kinase 2 Homo sapiens 70-74 14597612-6 2004 A dominant-negative p42 mutant, T161A, and posttranscriptional gene silencing of p42 with RNA(i)-impaired Thr-160 phosphorylation and activity of CDK2. Threonine 106-109 cyclin dependent kinase 2 Homo sapiens 146-150 14597612-7 2004 Purified p42 phosphorylated glutathione S-transferase-CDK2 at Thr-160 within the T-loop and activated its histone H1 kinase activity. Threonine 62-65 cyclin dependent kinase 2 Homo sapiens 54-58 14724573-2 2004 However, treatment with TRAIL in combination with subtoxic doses of roscovitine, a specific inhibitor of Cdc2 and Cdk2, induced rapid apoptosis in TRAIL-resistant glioma cells. Roscovitine 68-79 cyclin dependent kinase 2 Homo sapiens 114-118 14667929-7 2004 Immunoprecipitation showed that the formations of the CDK2-p21 and CDK4-p21 complex, but not the CDK2-p27 and CDK4-p27 complex, were increased in the DPTH-treated HUVEC. diphenylthiohydantoin 150-154 cyclin dependent kinase 2 Homo sapiens 97-101 14667929-8 2004 Kinase assay further demonstrated that both CDK2 and CDK4 kinase activities were decreased in the DPTH-treated HUVEC. diphenylthiohydantoin 98-102 cyclin dependent kinase 2 Homo sapiens 44-48 14667929-10 2004 In conclusion, these data suggest that DPTH inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 and CDK4 kinase activities, and finally interrupts the cell cycle. diphenylthiohydantoin 39-43 cyclin dependent kinase 2 Homo sapiens 136-140 14729633-3 2004 CYC202 (R-roscovitine) is a potent inhibitor of CDK2/cyclin E that is undergoing clinical trials. Roscovitine 8-21 cyclin dependent kinase 2 Homo sapiens 48-52 14657672-7 2004 Transient transfection assays were developed to show that the GFP-CDK2 docking site fusion protein (GFP-CIP) attenuates p53 activity in vivo and suppresses p21WAF1 induction which is similar to NU2058 but distinct from Roscovitine. Roscovitine 219-230 cyclin dependent kinase 2 Homo sapiens 62-70 15048068-3 2004 Here, we demonstrated that STI571 also induces growth arrest by activating the Chk2-Cdc25A-Cdk2 axis, a pathway complementary to p53 in the activation of G(1)/S cell cycle checkpoint. Imatinib Mesylate 27-33 cyclin dependent kinase 2 Homo sapiens 91-95 15011833-7 2004 p27kip1 is regulated by two mechanisms composed of a ubiquitin-proteasome system and proteolytic processing system that requires the phosphorylation of p27kip1 on Thr-187 by the cyclinE/Cdk2 complex followed by proteolytic degradation. Threonine 163-166 cyclin dependent kinase 2 Homo sapiens 186-190 14629982-6 2004 Our model was used to compare the ATP binding site of PfPK5 with that of the mammalian kinase CDK2. Adenosine Triphosphate 34-37 cyclin dependent kinase 2 Homo sapiens 94-98 14648095-11 2004 The expression of cdk1 and cdk2, important regulatory elements in the cell cycle, is downregulated following treatment with butyrate. Butyrates 124-132 cyclin dependent kinase 2 Homo sapiens 27-31 15587392-8 2004 Sodium butyrate inhibited the mRNA expression of CDK2, cyclinD2 and cyclinD1. Butyric Acid 0-15 cyclin dependent kinase 2 Homo sapiens 49-53 15587392-9 2004 ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 70-74 15587392-9 2004 ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Butyric Acid 9-24 cyclin dependent kinase 2 Homo sapiens 70-74 14659813-7 2003 Roscovitine, a selective CDK2 inhibitor, inhibited VSMC proliferation by both pRb-dependent and independent pathways and more potently in ISS-VSMCs than medial VSMCs. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 25-29 14551212-2 2003 To re-assess the precise relationship between the different phosphorylations of CDK2, and the influence of cyclins and CDK inhibitors upon them, we introduce here the use of the high resolution power of two-dimensional gel electrophoresis, combined to Tyr-15- or Thr-160-phosphospecific antibodies. Tyrosine 252-255 cyclin dependent kinase 2 Homo sapiens 80-84 14551212-2 2003 To re-assess the precise relationship between the different phosphorylations of CDK2, and the influence of cyclins and CDK inhibitors upon them, we introduce here the use of the high resolution power of two-dimensional gel electrophoresis, combined to Tyr-15- or Thr-160-phosphospecific antibodies. Threonine 263-266 cyclin dependent kinase 2 Homo sapiens 80-84 14506259-3 2003 The catalytic efficiency of CDK2-cyclin A is impaired 2000-, 10-, and 150-fold, when Pro+1, Lys+2, or Lys+3, respectively, is substituted with Ala in a short synthetic peptide substrate. Lysine 92-95 cyclin dependent kinase 2 Homo sapiens 28-32 14506259-3 2003 The catalytic efficiency of CDK2-cyclin A is impaired 2000-, 10-, and 150-fold, when Pro+1, Lys+2, or Lys+3, respectively, is substituted with Ala in a short synthetic peptide substrate. Alanine 143-146 cyclin dependent kinase 2 Homo sapiens 28-32 14506259-4 2003 Yet, in physiological substrates of both CDK2-cyclin A and CDK2-cyclin E, it is found that Lys+2, and, occasionally, both Lys+2 and Lys+3 together are replaced with suboptimal determinants. Lysine 91-94 cyclin dependent kinase 2 Homo sapiens 41-45 14506259-4 2003 Yet, in physiological substrates of both CDK2-cyclin A and CDK2-cyclin E, it is found that Lys+2, and, occasionally, both Lys+2 and Lys+3 together are replaced with suboptimal determinants. Lysine 91-94 cyclin dependent kinase 2 Homo sapiens 59-63 14659813-9 2003 The critical role for cyclin E-CDK2 enables the identification of the first agent that selectively inhibits ISS-VSMC proliferation. iss-vsmc 108-116 cyclin dependent kinase 2 Homo sapiens 31-35 14653808-2 2003 To achieve this, we used the chemical inhibitors roscovitine and olomoucine (which inhibit CDK2 preferentially), UCN-01 (which also inhibits CDK4/6) and p21 (as an intrinsic inhibitor). olomoucine 65-75 cyclin dependent kinase 2 Homo sapiens 91-95 14639003-5 2003 In in vitro studies, gefitinib arrested the cell cycle at G1 phase by inducing intrinsic cyclin-dependent kinase (cdk) inhibitors and following inhibition of cdk2. Gefitinib 21-30 cyclin dependent kinase 2 Homo sapiens 158-162 12954644-0 2003 Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. Vitamin D 0-9 cyclin dependent kinase 2 Homo sapiens 104-108 12954644-2 2003 We have previously shown that in the human prostate cancer cell line LN-CaP, 1,25-(OH)2D3 mediates an increase in cyclin-dependent kinase inhibitor p27Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G1. Calcitriol 77-89 cyclin dependent kinase 2 Homo sapiens 178-203 12954644-12 2003 Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. Calcitriol 22-34 cyclin dependent kinase 2 Homo sapiens 87-91 12954644-12 2003 Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. Calcitriol 22-34 cyclin dependent kinase 2 Homo sapiens 87-91 12954644-2 2003 We have previously shown that in the human prostate cancer cell line LN-CaP, 1,25-(OH)2D3 mediates an increase in cyclin-dependent kinase inhibitor p27Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G1. Calcitriol 77-89 cyclin dependent kinase 2 Homo sapiens 205-209 12954644-13 2003 These data suggest that Cdk2 mislocalization is central to the antiproliferative effects of 1,25-(OH)2D3. Calcitriol 92-104 cyclin dependent kinase 2 Homo sapiens 24-28 12954644-11 2003 Interestingly, 1,25-(OH)2D3 decreased nuclear Cdk2 levels as assessed by subcellular fractionation and confocal microscopy. Calcitriol 15-27 cyclin dependent kinase 2 Homo sapiens 46-50 12954644-12 2003 Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. Calcitriol 22-34 cyclin dependent kinase 2 Homo sapiens 14-18 12954644-12 2003 Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. Calcitriol 22-34 cyclin dependent kinase 2 Homo sapiens 87-91 14614451-4 2003 In mechanistic studies related its effect on cell cycle progression, silibinin treatment resulted in an upregulation of Kip1/p27 and Cip1/p21 protein as well as mRNA levels, and decreased CDK2, CDK4, cyclin E and cyclin D1 protein levels together with an inhibition in CDK2 and CDK4 kinase activities. Silybin 69-78 cyclin dependent kinase 2 Homo sapiens 269-273 12819186-0 2003 Panaxadiol selectively inhibits cyclin A-associated Cdk2 activity by elevating p21WAF1/CIP1 protein levels in mammalian cells. panaxadiol 0-10 cyclin dependent kinase 2 Homo sapiens 52-56 14614451-4 2003 In mechanistic studies related its effect on cell cycle progression, silibinin treatment resulted in an upregulation of Kip1/p27 and Cip1/p21 protein as well as mRNA levels, and decreased CDK2, CDK4, cyclin E and cyclin D1 protein levels together with an inhibition in CDK2 and CDK4 kinase activities. Silybin 69-78 cyclin dependent kinase 2 Homo sapiens 188-192 14504459-0 2003 Getting in the ring: proline-directed substrate specificity in the cell cycle proteins Cdc14 and CDK2-cyclinA3. Proline 21-28 cyclin dependent kinase 2 Homo sapiens 97-101 14646596-3 2003 In order to define kinase properties of CDK2 and CDK4 in complex with cycline A or cycline D1 in relation to their respective role in cell cycling regulation, we examined enzymatic properties of both CDK4/cycline D1 and CDK2/cycline A in vitro. cycline a 70-79 cyclin dependent kinase 2 Homo sapiens 40-44 14587026-1 2003 All-trans retinoic acid (ATRA) can down regulate the anti-apoptotic protein Bcl-2 and the cell cycle proteins cyclin D1 and cdk2 in estrogen receptor-positive breast cancer cells. Tretinoin 0-23 cyclin dependent kinase 2 Homo sapiens 124-128 14587026-1 2003 All-trans retinoic acid (ATRA) can down regulate the anti-apoptotic protein Bcl-2 and the cell cycle proteins cyclin D1 and cdk2 in estrogen receptor-positive breast cancer cells. Tretinoin 25-29 cyclin dependent kinase 2 Homo sapiens 124-128 14587026-4 2003 In both cell lines ATRA and 9-cis RA induced the most profound decreases in cyclin D1 and cdk2 expression and also mediated the largest growth inhibition. Radium 21-23 cyclin dependent kinase 2 Homo sapiens 90-94 14646596-3 2003 In order to define kinase properties of CDK2 and CDK4 in complex with cycline A or cycline D1 in relation to their respective role in cell cycling regulation, we examined enzymatic properties of both CDK4/cycline D1 and CDK2/cycline A in vitro. cycline d1 83-93 cyclin dependent kinase 2 Homo sapiens 40-44 14646596-3 2003 In order to define kinase properties of CDK2 and CDK4 in complex with cycline A or cycline D1 in relation to their respective role in cell cycling regulation, we examined enzymatic properties of both CDK4/cycline D1 and CDK2/cycline A in vitro. cycline d1 205-215 cyclin dependent kinase 2 Homo sapiens 40-44 14646596-4 2003 Association constant, Km for ATP in CDK4/cyclin D1 was found as 418 microM, a value unusually high whereas CDK2/cyclin A was 23 microM, a value close to most of other regulatory protein kinases. Adenosine Triphosphate 29-32 cyclin dependent kinase 2 Homo sapiens 107-111 14646596-9 2003 Also, analysis of phosphorylated serine/threonine sites on RB catalyzed by CDK4/cyclin D1 and CDK2/cyclin A showed significant differences in their preference of phosphorylation sites in RB C-terminal domain. Serine 33-39 cyclin dependent kinase 2 Homo sapiens 94-98 14646596-9 2003 Also, analysis of phosphorylated serine/threonine sites on RB catalyzed by CDK4/cyclin D1 and CDK2/cyclin A showed significant differences in their preference of phosphorylation sites in RB C-terminal domain. Threonine 40-49 cyclin dependent kinase 2 Homo sapiens 94-98 12857729-3 2003 Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Serine 24-30 cyclin dependent kinase 2 Homo sapiens 0-4 14550307-0 2003 SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2. SU 9516 0-6 cyclin dependent kinase 2 Homo sapiens 85-89 14550307-3 2003 The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Adenosine Triphosphate 44-47 cyclin dependent kinase 2 Homo sapiens 52-56 14550307-4 2003 Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. SU 9516 11-17 cyclin dependent kinase 2 Homo sapiens 27-31 14550307-4 2003 Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. Adenosine Triphosphate 66-69 cyclin dependent kinase 2 Homo sapiens 27-31 14550307-6 2003 The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. SU 9516 31-37 cyclin dependent kinase 2 Homo sapiens 47-51 12970441-5 2003 Synthetic peptides spanning HPV16 amino acid residues 9 to 38 also activate CDK2. Peptides 10-18 cyclin dependent kinase 2 Homo sapiens 76-80 12970441-6 2003 Peptides containing this sequence that carry biotin on the carboxy terminus, as well as a photoactivated cross-linking group (benzophenone), also activate the complex and covalently associate with the CDK2/cyclin A complex in a specific manner requiring UV. Biotin 45-51 cyclin dependent kinase 2 Homo sapiens 201-205 12970441-6 2003 Peptides containing this sequence that carry biotin on the carboxy terminus, as well as a photoactivated cross-linking group (benzophenone), also activate the complex and covalently associate with the CDK2/cyclin A complex in a specific manner requiring UV. benzophenone 126-138 cyclin dependent kinase 2 Homo sapiens 201-205 12969788-6 2003 Furthermore, the synthetic bile acids increased the levels of Cdk inhibitor, p21WAF1/CIP1, expression and activated the reporter construct of p21WAF1/CIP1 promoter in p53-independent manner, and p21WAF1/CIP1 proteins induced by the synthetic bile acid derivatives were associated with Cdk2 and proliferating cell nuclear antigen. Bile Acids and Salts 27-37 cyclin dependent kinase 2 Homo sapiens 285-289 12969788-6 2003 Furthermore, the synthetic bile acids increased the levels of Cdk inhibitor, p21WAF1/CIP1, expression and activated the reporter construct of p21WAF1/CIP1 promoter in p53-independent manner, and p21WAF1/CIP1 proteins induced by the synthetic bile acid derivatives were associated with Cdk2 and proliferating cell nuclear antigen. Bile Acids and Salts 27-36 cyclin dependent kinase 2 Homo sapiens 285-289 12941317-0 2003 Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis. anilinopyrazole 0-15 cyclin dependent kinase 2 Homo sapiens 29-33 12941325-2 2003 Comparison of their experimentally-determined binding modes and emerging structure-activity trends led to the development of potent and selective imidazo[1,2-a]pyridine inhibitors for CDK4 and in particular CDK2. imidazo(1,2-a)pyridine 146-168 cyclin dependent kinase 2 Homo sapiens 207-211 12907249-0 2003 Inhibition of MG-63 cell cycle progression by synthetic vitamin D3 analogs mediated by p27, Cdk2, cyclin E, and the retinoblastoma protein. Cholecalciferol 56-66 cyclin dependent kinase 2 Homo sapiens 92-96 12941338-1 2003 A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. o(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines 12-62 cyclin dependent kinase 2 Homo sapiens 139-143 12941338-3 2003 The crystal structure of the 4"-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue. 4"-carboxamide 29-43 cyclin dependent kinase 2 Homo sapiens 87-91 12941338-3 2003 The crystal structure of the 4"-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue. carboxamide 32-43 cyclin dependent kinase 2 Homo sapiens 87-91 12941338-3 2003 The crystal structure of the 4"-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue. Aspartic Acid 235-244 cyclin dependent kinase 2 Homo sapiens 87-91 13678583-4 2003 Cell cycle arrest occurs despite p21 degradation via Tyr(15) inhibitory phosphorylation of cdk2 and differs from the classical p21-dependent checkpoint elicited by ionizing radiation. Tyrosine 53-56 cyclin dependent kinase 2 Homo sapiens 91-95 12852944-0 2003 3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors. 3,5,6-trisubstituted naphthostyrils 0-35 cyclin dependent kinase 2 Homo sapiens 39-43 12852944-1 2003 A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). 3,5,6-trisubstituted naphthostyril 17-51 cyclin dependent kinase 2 Homo sapiens 154-179 12852944-1 2003 A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). 3,5,6-trisubstituted naphthostyril 17-51 cyclin dependent kinase 2 Homo sapiens 181-185 12852944-2 2003 These compounds, particularly molecules with side-chain modifications providing additional hydrogen bonding capability, were demonstrated to be potent CDK2 inhibitors with cellular activities consistent with CDK2 inhibition. Hydrogen 91-99 cyclin dependent kinase 2 Homo sapiens 151-155 12852944-4 2003 The X-ray crystal structure of a 2-aminoethyleneamine derivative bound to CDK2, refined to 2.5A resolution, is presented. 2-aminoethyleneamine 33-53 cyclin dependent kinase 2 Homo sapiens 74-78 12943967-2 2003 PBOX-21-induced G1 arrest is preceded by both a decrease in CDK2 kinase activity, which is critical for the G1/S transition, and a downregulation in cyclin D(3) protein expression levels, suggesting that these two events may be crucially involved in the mediation of the cell cycle arrest. 7-((diethylcarbamoyl)oxy)-6-p-tolylpyrrolo(2,1-d)(1,5)benzoxazepine 0-7 cyclin dependent kinase 2 Homo sapiens 60-64 12869192-6 2003 Three other kinases [cyclin-dependent protein kinase 2 (CDK2), phosphorylase kinase and glycogen synthase kinase 3beta] exhibit approximately 10-fold weaker affinity for TBB than CK2. 4,5,6,7-tetrabromobenzotriazole 170-173 cyclin dependent kinase 2 Homo sapiens 21-54 12869192-6 2003 Three other kinases [cyclin-dependent protein kinase 2 (CDK2), phosphorylase kinase and glycogen synthase kinase 3beta] exhibit approximately 10-fold weaker affinity for TBB than CK2. 4,5,6,7-tetrabromobenzotriazole 170-173 cyclin dependent kinase 2 Homo sapiens 56-60 12869192-7 2003 We report the crystal structure of TBB in complex with phospho-CDK2-cyclin A at 2.2 A resolution and compare the interactions with those observed for TBB bound to CK2. 4,5,6,7-tetrabromobenzotriazole 35-38 cyclin dependent kinase 2 Homo sapiens 63-67 12869192-9 2003 In CDK2, each of the four bromine atoms makes polar contacts either to main chain oxygens in the hinge region of the kinase or to water molecules, in addition to several van der Waals contacts. Bromine 26-33 cyclin dependent kinase 2 Homo sapiens 3-7 12869192-9 2003 In CDK2, each of the four bromine atoms makes polar contacts either to main chain oxygens in the hinge region of the kinase or to water molecules, in addition to several van der Waals contacts. Oxygen 82-89 cyclin dependent kinase 2 Homo sapiens 3-7 12869192-9 2003 In CDK2, each of the four bromine atoms makes polar contacts either to main chain oxygens in the hinge region of the kinase or to water molecules, in addition to several van der Waals contacts. Water 130-135 cyclin dependent kinase 2 Homo sapiens 3-7 12869192-10 2003 The mode of binding of TBB to CDK2 is different from that to CK2. 4,5,6,7-tetrabromobenzotriazole 23-26 cyclin dependent kinase 2 Homo sapiens 30-34 12869192-11 2003 TBB in CDK2 is displaced more towards the hinge region between the N- and C-terminal lobes and rotated relative to TBB in CK2. 4,5,6,7-tetrabromobenzotriazole 0-3 cyclin dependent kinase 2 Homo sapiens 7-11 12869192-11 2003 TBB in CDK2 is displaced more towards the hinge region between the N- and C-terminal lobes and rotated relative to TBB in CK2. 4,5,6,7-tetrabromobenzotriazole 115-118 cyclin dependent kinase 2 Homo sapiens 7-11 12869192-12 2003 The ATP binding pocket is wider in CDK2 than in CK2 resulting in fewer van der Waals contacts but TBB in CK2 does not contact the hinge. Adenosine Triphosphate 4-7 cyclin dependent kinase 2 Homo sapiens 35-39 12676926-4 2003 Furthermore, cyclin A/CDK1/2, cyclin B/CDK1/2, and cyclin E/CDK2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. Threonine 127-136 cyclin dependent kinase 2 Homo sapiens 60-64 12690110-3 2003 Using human erythroleukemic K562 cells as model system, we demonstrated that resveratrol induces a remarkable gamma-globin synthesis, the erythroid differentiation being linked to impairment of cell proliferation, increased p21Cip1 expression and inhibition of cdk2 activity. Resveratrol 77-88 cyclin dependent kinase 2 Homo sapiens 261-265 12824044-1 2003 Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). 1H-pyrazolo(3,4-b)pyridine 30-56 cyclin dependent kinase 2 Homo sapiens 105-109 12824044-1 2003 Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). 1H-pyrazolo(3,4-b)pyridine 30-56 cyclin dependent kinase 2 Homo sapiens 170-174 12824044-1 2003 Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). 21h 130-133 cyclin dependent kinase 2 Homo sapiens 105-109 12824044-1 2003 Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). 21h 130-133 cyclin dependent kinase 2 Homo sapiens 170-174 12824044-3 2003 A solid state structure of 21j, a close di-fluoro analogue, bound to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone. Adenosine Triphosphate 122-125 cyclin dependent kinase 2 Homo sapiens 69-73 12824044-3 2003 A solid state structure of 21j, a close di-fluoro analogue, bound to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone. purine 126-132 cyclin dependent kinase 2 Homo sapiens 69-73 12852762-2 2003 In this computational study, we have applied a continuum solvent model to study the interactions between cyclin-dependent kinase 2 (CDK2) and analogues of the clinically tested anticancer agent flavopiridol. alvocidib 194-206 cyclin dependent kinase 2 Homo sapiens 105-130 12852762-2 2003 In this computational study, we have applied a continuum solvent model to study the interactions between cyclin-dependent kinase 2 (CDK2) and analogues of the clinically tested anticancer agent flavopiridol. alvocidib 194-206 cyclin dependent kinase 2 Homo sapiens 132-136 12852762-5 2003 Our model was first validated through a study on the binding of a number of flavopiridol derivatives to CDK2, and its ability to identify potent inhibitors was observed. alvocidib 76-88 cyclin dependent kinase 2 Homo sapiens 104-108 12714602-3 2003 The data presented here indicate that the consecutive actions of ATR-CHK1 and CDK2 kinases are involved in this phosphorylation in the presence of hydroxyurea. Hydroxyurea 147-158 cyclin dependent kinase 2 Homo sapiens 78-82 12767926-4 2003 Olomoucine or roscovitine, specific Cdks inhibitors, effectively prevent mitochondrial membrane depolarization as well as apoptotic cell death in panaxadiol-treated cells. olomoucine 0-10 cyclin dependent kinase 2 Homo sapiens 36-40 12805303-5 2003 In the lactacystin-treated OLGcs, there was a dose-dependent decrease in the number of cells incorporating bromodeoxyuridine and in the activity of the complexes cyclin D-cdk4 and cyclin E-cdk2. lactacystin 7-18 cyclin dependent kinase 2 Homo sapiens 189-193 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. imidazole indolinone 58-78 cyclin dependent kinase 2 Homo sapiens 34-38 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. imidazole indolinone 58-78 cyclin dependent kinase 2 Homo sapiens 266-270 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. SU 9516 91-97 cyclin dependent kinase 2 Homo sapiens 34-38 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. SU 9516 91-97 cyclin dependent kinase 2 Homo sapiens 266-270 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. pyrrolyllactone 209-224 cyclin dependent kinase 2 Homo sapiens 34-38 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. pyrrolyllactone 209-224 cyclin dependent kinase 2 Homo sapiens 266-270 12749903-3 2003 Based on the crystal structure of CDK2 in complex with an imidazole indolinone compound 1 (SU9516), lead optimization through modeling, synthesis, and SAR studies has led to the discovery of a novel series of pyrrolyllactone and pyrrolyllactam indolinones as potent CDK2 inhibitors. pyrrolyllactam indolinones 229-255 cyclin dependent kinase 2 Homo sapiens 34-38 12781329-0 2003 Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip). pentagalloylglucose 65-84 cyclin dependent kinase 2 Homo sapiens 125-129 12781329-0 2003 Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip). pentagalloylglucose 65-84 cyclin dependent kinase 2 Homo sapiens 116-119 12781329-7 2003 p27(Kip) and p21(Cip), inhibitors of cyclin/CDK complexes in G1-phase, were gradually increased after 5GG treatment in a time-dependent manner and the induction of p21(Cip) was correlated with an increase in p53 levels. pentagalloylglucose 102-105 cyclin dependent kinase 2 Homo sapiens 44-47 12781329-8 2003 These results suggest that the suppression of cell-cycle progression in the G1 phase by 5GG was mediated in MCF-7 cells, at least in part, by either the inhibition of cyclin D/CDK4 and cyclin E/CDK2 activity or the induction of the CDK inhibitors p27(Kip) and p21(Cip). pentagalloylglucose 88-91 cyclin dependent kinase 2 Homo sapiens 194-198 12781329-8 2003 These results suggest that the suppression of cell-cycle progression in the G1 phase by 5GG was mediated in MCF-7 cells, at least in part, by either the inhibition of cyclin D/CDK4 and cyclin E/CDK2 activity or the induction of the CDK inhibitors p27(Kip) and p21(Cip). pentagalloylglucose 88-91 cyclin dependent kinase 2 Homo sapiens 176-179 12767926-4 2003 Olomoucine or roscovitine, specific Cdks inhibitors, effectively prevent mitochondrial membrane depolarization as well as apoptotic cell death in panaxadiol-treated cells. Roscovitine 14-25 cyclin dependent kinase 2 Homo sapiens 36-40 12767926-4 2003 Olomoucine or roscovitine, specific Cdks inhibitors, effectively prevent mitochondrial membrane depolarization as well as apoptotic cell death in panaxadiol-treated cells. panaxadiol 146-156 cyclin dependent kinase 2 Homo sapiens 36-40 12767926-5 2003 Thus, panaxadiol-treatment induces cell death-dependent activation of Cdk2 kinase activity, which is functionally associated with depolarization of mitochondrial membrane potential and subsequent cytochrome c release. panaxadiol 6-16 cyclin dependent kinase 2 Homo sapiens 70-74 12809528-6 2003 All were cocrystallized with CDK2 and found to localize in the ATP-binding pocket of the kinase. Adenosine Triphosphate 63-66 cyclin dependent kinase 2 Homo sapiens 29-33 12706118-5 2003 We have found up-regulated levels of the cyclin-dependent kinase 2 (cdk2) protein in HDF expressing 143(ala) mutant p53 as compared to senescent controls, together with an increase in p21-free cdk2 which, in conjunction with cyclin E, is able to form an active kinase which can phosphorylate the retinoblastoma protein. Alanine 104-107 cyclin dependent kinase 2 Homo sapiens 41-66 12800980-2 2003 Dexamethasone (DXM) treatment of PHA-stimulated lymphocytes induced a decrease in CDK2 mRNA expression without any change in mRNA stability. Dexamethasone 0-13 cyclin dependent kinase 2 Homo sapiens 82-86 12800980-2 2003 Dexamethasone (DXM) treatment of PHA-stimulated lymphocytes induced a decrease in CDK2 mRNA expression without any change in mRNA stability. Dexamethasone 15-18 cyclin dependent kinase 2 Homo sapiens 82-86 12800980-3 2003 This glucocorticoid-induced decrease in CDK2 mRNA expression could be suppressed by cycloheximide treatment. Cycloheximide 84-97 cyclin dependent kinase 2 Homo sapiens 40-44 12706118-5 2003 We have found up-regulated levels of the cyclin-dependent kinase 2 (cdk2) protein in HDF expressing 143(ala) mutant p53 as compared to senescent controls, together with an increase in p21-free cdk2 which, in conjunction with cyclin E, is able to form an active kinase which can phosphorylate the retinoblastoma protein. Alanine 104-107 cyclin dependent kinase 2 Homo sapiens 68-72 12745075-1 2003 The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on a conserved threonine residue, T160, in a cyclin dependent manner. Threonine 161-170 cyclin dependent kinase 2 Homo sapiens 141-145 12745075-1 2003 The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on a conserved threonine residue, T160, in a cyclin dependent manner. 2,2',2''-trichlorotriethylamine 180-184 cyclin dependent kinase 2 Homo sapiens 141-145 12767603-1 2003 A series of 1,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines 15-19, 30-38 capable of selectively inhibiting CDK2 activity were synthesized by derivatization at C-4, C-6 and N-1 with various amines and lower alkyl groups. 1,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines 12-59 cyclin dependent kinase 2 Homo sapiens 107-111 12767603-1 2003 A series of 1,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines 15-19, 30-38 capable of selectively inhibiting CDK2 activity were synthesized by derivatization at C-4, C-6 and N-1 with various amines and lower alkyl groups. Amines 189-195 cyclin dependent kinase 2 Homo sapiens 107-111 12767603-3 2003 In our series, 4-anilino compounds exhibited better CDK2 inhibitory activity and antitumor activity compared to 4-benzyl compounds. 4-anilino 15-24 cyclin dependent kinase 2 Homo sapiens 52-56 12646262-8 2003 The addition of butyrolactone I, which is an inhibitor of CDK1 and CDK2, to the p53-negative cells reduced the floating round cell population and induced the disappearance of cyclin B1. 4-Butyrolactone 16-29 cyclin dependent kinase 2 Homo sapiens 67-71 12684681-6 2003 In addition, trichostatin markedly enhanced the binding of p27 with CDK2 and CDK4. trichostatin A 13-25 cyclin dependent kinase 2 Homo sapiens 68-72 12492401-8 2003 Western blot analysis also shows that DHA greatly reduces the level of cyclin A, while increasing the level of p21 WAF1, a cellular inhibitor of cyclin A/cyclin-dependent kinase 2 (cdk2) activity. Docosahexaenoic Acids 38-41 cyclin dependent kinase 2 Homo sapiens 181-185 12492401-11 2003 By this pathway, low doses of DHA increase ceramide levels, which leads to inhibition of cdk2 activity and stimulation of PP1 and PP2A. Docosahexaenoic Acids 30-33 cyclin dependent kinase 2 Homo sapiens 89-93 12492401-11 2003 By this pathway, low doses of DHA increase ceramide levels, which leads to inhibition of cdk2 activity and stimulation of PP1 and PP2A. Ceramides 43-51 cyclin dependent kinase 2 Homo sapiens 89-93 12659774-0 2003 Synthesis of potent oxindole CDK2 inhibitors. 2-oxindole 20-28 cyclin dependent kinase 2 Homo sapiens 29-33 12659774-1 2003 A series of oxindole CDK2 inhibitors was synthesized. 2-oxindole 12-20 cyclin dependent kinase 2 Homo sapiens 21-25 12659774-3 2003 This substitution afforded agents with increased potency relative to the parent indolinone and nanomolar range IC(50) against the CDK2 enzyme and two cancer cell lines. Oxindoles 80-90 cyclin dependent kinase 2 Homo sapiens 130-134 12689523-6 2003 Also, beta-lapachone suppressed the cyclin-dependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. beta-lapachone 6-20 cyclin dependent kinase 2 Homo sapiens 62-66 12647787-7 2003 PG inhibited cyclin E, cdk2, p27 and p21, the induction of the cyclin A-cdk2 and cyclin E-cdk2 kinase activity, and the phosphorylation of Rb in leukaemic Jurkat cells. Prodigiosin 0-2 cyclin dependent kinase 2 Homo sapiens 23-27 12647787-7 2003 PG inhibited cyclin E, cdk2, p27 and p21, the induction of the cyclin A-cdk2 and cyclin E-cdk2 kinase activity, and the phosphorylation of Rb in leukaemic Jurkat cells. Prodigiosin 0-2 cyclin dependent kinase 2 Homo sapiens 72-76 12647787-7 2003 PG inhibited cyclin E, cdk2, p27 and p21, the induction of the cyclin A-cdk2 and cyclin E-cdk2 kinase activity, and the phosphorylation of Rb in leukaemic Jurkat cells. Prodigiosin 0-2 cyclin dependent kinase 2 Homo sapiens 72-76 12599217-4 2003 Cell cycle kinetic analysis demonstrated that ZD1839 induces a delay in cell cycle progression and a G1 arrest together with a partial G2/M block; this was associated with increased expression of both p27(KIP1) and p21(CIP1/WAF1) cyclin-dependent kinase (CDK) inhibitors. Gefitinib 46-52 cyclin dependent kinase 2 Homo sapiens 255-258 12643928-1 2003 1H-Pyrazolo[3,4-b]pyridine 3 (SQ-67563) has been shown to be a potent, selective inhibitor of CDK1/CDK2 in vitro. 1h-pyrazolo[3,4-b]pyridine 3 0-28 cyclin dependent kinase 2 Homo sapiens 99-103 12643928-1 2003 1H-Pyrazolo[3,4-b]pyridine 3 (SQ-67563) has been shown to be a potent, selective inhibitor of CDK1/CDK2 in vitro. SQ-67563 30-38 cyclin dependent kinase 2 Homo sapiens 99-103 12643928-3 2003 The solid state structure of 3 bound to CDK2 shows 3 resides coincident with the ATP purine binding site and forms important H-bonding interactions with Leu83 on the protein backbone. Adenosine Triphosphate 81-84 cyclin dependent kinase 2 Homo sapiens 40-44 12643928-3 2003 The solid state structure of 3 bound to CDK2 shows 3 resides coincident with the ATP purine binding site and forms important H-bonding interactions with Leu83 on the protein backbone. purine 85-91 cyclin dependent kinase 2 Homo sapiens 40-44 12689523-7 2003 Furthermore, this compound induced the levels of the Cdk inhibitor p21(WAF1/CIP1) expression in a p53-independent manner, and the p21 proteins that were induced by beta-lapachone were associated with Cdk2. beta-lapachone 164-178 cyclin dependent kinase 2 Homo sapiens 200-204 12820434-8 2003 CONCLUSION: Overall, these results suggest that p21Cip1 is a critical target in PA-mediated cell growth inhibition in RCC cells playing a key role in CDK2 inactivation, hypophosphorylation of pRb and subsequent G1 cell cycle arrest. Protactinium 80-82 cyclin dependent kinase 2 Homo sapiens 150-154 12820434-7 2003 Reduced phosphorylation of the retinoblastoma protein (Rb) and CDK2 activity, increased expression of p21Cip1 and enhanced binding of p21Cip1 to CDK2 were observed following treatment with PA. Protactinium 189-191 cyclin dependent kinase 2 Homo sapiens 63-67 12820434-7 2003 Reduced phosphorylation of the retinoblastoma protein (Rb) and CDK2 activity, increased expression of p21Cip1 and enhanced binding of p21Cip1 to CDK2 were observed following treatment with PA. Protactinium 189-191 cyclin dependent kinase 2 Homo sapiens 145-149 12920809-4 2003 Targeting of Stat3 using antisense oligonucleotide which directed against the translation site resulted in growth inhibition, downregulation of Stat3, p-Stat3, Cyclins and CDKs, and up-regulation of p21 and p27. Oligonucleotides 35-50 cyclin dependent kinase 2 Homo sapiens 172-176 12663518-8 2003 IP6 inhibited kinase activities associated with CDK2, 4 and 6, and cyclin E and D1. Phytic Acid 0-3 cyclin dependent kinase 2 Homo sapiens 48-52 12676582-5 2003 Surprisingly, osteosarcomas and Rb-negative cervical cancers continued to proliferate after depletion of CDK2 through antisense oligonucleotides or small interfering (si) RNA. Oligonucleotides 128-144 cyclin dependent kinase 2 Homo sapiens 105-109 12475985-0 2003 Inhibition of cdk2 activating phosphorylation by mevastatin. mevastatin 49-59 cyclin dependent kinase 2 Homo sapiens 14-18 12598612-5 2003 Death and mitochondrial dysfunction induced by lactacystin and other pharmacological inhibitors of the proteasome were prevented by flavopiridol, a specific inhibitor of cyclin-dependent kinases (Cdks). lactacystin 47-58 cyclin dependent kinase 2 Homo sapiens 196-200 12598612-5 2003 Death and mitochondrial dysfunction induced by lactacystin and other pharmacological inhibitors of the proteasome were prevented by flavopiridol, a specific inhibitor of cyclin-dependent kinases (Cdks). alvocidib 132-144 cyclin dependent kinase 2 Homo sapiens 196-200 12598612-6 2003 Molecular expression of the Cdk inhibitors p16 or p27, or of dominant-negative Cdk2, Cdk4, or Cdk6 was also protective against lactacystin-induced death. lactacystin 127-138 cyclin dependent kinase 2 Homo sapiens 79-83 12475985-1 2003 Phosphorylation of cdk2 on threonine 160 is essential for kinase activity. Threonine 27-36 cyclin dependent kinase 2 Homo sapiens 19-23 12475985-2 2003 Mevastatin, an inhibitor of cholesterol synthesis, inhibits cell growth through inhibition of cdk2 and this has been suggested to be due to enhancement of p21 levels. mevastatin 0-10 cyclin dependent kinase 2 Homo sapiens 94-98 12475985-2 2003 Mevastatin, an inhibitor of cholesterol synthesis, inhibits cell growth through inhibition of cdk2 and this has been suggested to be due to enhancement of p21 levels. Cholesterol 28-39 cyclin dependent kinase 2 Homo sapiens 94-98 12475985-3 2003 In a prostate cancer cell line, PC3, mevastatin treatment led to elevated levels of p21 and caused a small increase in the p21 associated with cdk2. mevastatin 37-47 cyclin dependent kinase 2 Homo sapiens 143-147 12475985-5 2003 Using RNA interference we show that mevastatin inhibits cdk2 activity despite lack of induction of p21, p27, and p57. mevastatin 36-46 cyclin dependent kinase 2 Homo sapiens 56-60 12475985-7 2003 Phosphorylation of cdk2 from mevastatin-treated cells with exogenous cyclin-dependent kinase (cdk)-activating enzymes restored its functional activity. mevastatin 29-39 cyclin dependent kinase 2 Homo sapiens 19-23 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. mevastatin 27-37 cyclin dependent kinase 2 Homo sapiens 47-51 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. mevastatin 27-37 cyclin dependent kinase 2 Homo sapiens 127-131 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. mevastatin 27-37 cyclin dependent kinase 2 Homo sapiens 127-131 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. Threonine 100-103 cyclin dependent kinase 2 Homo sapiens 47-51 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. Threonine 100-103 cyclin dependent kinase 2 Homo sapiens 127-131 12475985-9 2003 These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level. Threonine 100-103 cyclin dependent kinase 2 Homo sapiens 127-131 14695446-9 2003 The Cdk2 inhibitor, roscovitine, decreased the resistance to apoptosis on etoposide-treated UMG1-2. Etoposide 74-83 cyclin dependent kinase 2 Homo sapiens 4-8 12479875-0 2003 Down-regulation and decreased activity of cyclin-dependent kinase 2 in H2O2-induced premature senescence. Hydrogen Peroxide 71-75 cyclin dependent kinase 2 Homo sapiens 42-67 12479875-5 2003 RNase protection assay, semi-quantitative RT-PCR, Western blot and kinase assay showed that the mRNA level, protein and kinase activity of CdK2 are decreased at 72h after H2O2 stress. Hydrogen Peroxide 171-175 cyclin dependent kinase 2 Homo sapiens 139-143 12519061-5 2003 A selectivity study performed on 26 kinases shows that aloisine A is highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3 alpha/beta; the two latter enzymes have been implicated in Alzheimer"s disease. 7-n-butyl-6-(4'-hydroxyphenyl)-5H-pyrrolo(2,3b)pyrazine 55-65 cyclin dependent kinase 2 Homo sapiens 105-109 12519061-6 2003 Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. Aloisine 53-61 cyclin dependent kinase 2 Homo sapiens 48-52 12519061-6 2003 Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. aloisines 100-109 cyclin dependent kinase 2 Homo sapiens 48-52 12519061-6 2003 Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. Adenosine Triphosphate 143-146 cyclin dependent kinase 2 Homo sapiens 48-52 14977434-5 2003 Moreover, the kinase activities of cyclin E and Cdk2 were inhibited by resveratrol without alteration of their protein levels. Resveratrol 71-82 cyclin dependent kinase 2 Homo sapiens 48-52 14695446-0 2003 Human cytomegalovirus (HCMV) IE1 plays role in resistance to apoptosis with etoposide in cancer cell line by Cdk2 accumulation. Etoposide 76-85 cyclin dependent kinase 2 Homo sapiens 109-113 14695446-8 2003 Cellular expression of Cdk2 was increased in UMG1- 2 after etoposide treatment while the expression of E2F-1 in UMG1-2 was decreased as compared with that in U373MG. Etoposide 59-68 cyclin dependent kinase 2 Homo sapiens 23-27 14695446-9 2003 The Cdk2 inhibitor, roscovitine, decreased the resistance to apoptosis on etoposide-treated UMG1-2. Roscovitine 20-31 cyclin dependent kinase 2 Homo sapiens 4-8 12482427-6 2003 However, the derivative bearing an isosteric 5-formyl group, 2,6-diamino-4-cyclohexylmethoxy-pyrimidine-5-carbaldehyde, showed modest activity (IC(50) vs cdk1/cyclinB1=35+/-3 microM and cdk2/cyclinA3=43+/-3 microM). 2,6-diamino-4-cyclohexylmethoxy-pyrimidine-5-carbaldehyde 61-118 cyclin dependent kinase 2 Homo sapiens 186-190 12482427-8 2003 The intramolecular H-bond deduced from the structure with NU6027 bound to cdk2 is not evident in the structure with the corresponding formyl compound. 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 58-64 cyclin dependent kinase 2 Homo sapiens 74-78 12678910-2 2003 In our laboratories, a variety of selective and potent low molecular weight inhibitors directed against the ATP binding sites of the Cdk1, Cdk2 have been developed. Adenosine Triphosphate 108-111 cyclin dependent kinase 2 Homo sapiens 139-143 12678911-3 2003 In this article, we review the structural biology work that has led to a precise knowledge of the interactions between CDK2 and small organic molecules binding to its ATP pocket that are determinant for inhibitory activity. Adenosine Triphosphate 167-170 cyclin dependent kinase 2 Homo sapiens 119-123 12463761-3 2002 Like other dual-specificity phosphatases, Cdc25 contains an active site cysteine whose pK(a) of 5.9 can be measured in pH-dependent kinetics using both small molecule and protein substrates such as Cdk2-pTpY/CycA. Cysteine 72-80 cyclin dependent kinase 2 Homo sapiens 198-202 12533675-3 2003 Given the ability of cyclin/cyclin-dependent kinase 2 antagonists to kill transformed cells, we surmised that flavopiridol may stabilize E2F1 and enhance apoptosis via repression of Mcl-1. alvocidib 110-122 cyclin dependent kinase 2 Homo sapiens 28-53 12457721-1 2003 Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 104-108 12457721-1 2003 Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). flavone 28-35 cyclin dependent kinase 2 Homo sapiens 104-108 12457721-9 2003 Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 31-35 12457721-9 2003 Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 71-75 12722479-9 2003 Adriamycin-induced G1/S arrest seems to be realized via cyclin-cdk complexes activity-independent way involving antiproliferative targets downstream of cyclin E-cdk2 and cyclin A-cdk2 complexes. Doxorubicin 0-10 cyclin dependent kinase 2 Homo sapiens 161-165 12722479-9 2003 Adriamycin-induced G1/S arrest seems to be realized via cyclin-cdk complexes activity-independent way involving antiproliferative targets downstream of cyclin E-cdk2 and cyclin A-cdk2 complexes. Doxorubicin 0-10 cyclin dependent kinase 2 Homo sapiens 179-183 12501191-3 2002 Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu ("RXL" or "KXL") substrate recruitment motifs. Serine 122-125 cyclin dependent kinase 2 Homo sapiens 158-162 12501191-3 2002 Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu ("RXL" or "KXL") substrate recruitment motifs. Arginine 132-135 cyclin dependent kinase 2 Homo sapiens 158-162 12501191-3 2002 Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu ("RXL" or "KXL") substrate recruitment motifs. Lysine 136-139 cyclin dependent kinase 2 Homo sapiens 158-162 12432547-2 2002 We show here that CYC202 (R-roscovitine) is a potent inhibitor of recombinant CDK2/cyclin E kinase activity (IC(50) = 0.10 microM) with an average cytotoxic IC(50) of 15.2 microM in a panel of 19 human tumour cell lines, and we also demonstrate selectivity for rapidly proliferating cells over non-proliferating cells. Roscovitine 26-39 cyclin dependent kinase 2 Homo sapiens 78-82 12463761-7 2002 Our pH-dependent studies, including one-turnover kinetics, solvent kinetic isotope effects, equilibrium perturbation, substrate depletion, and viscosity measurements, show that the monoprotonated phosphate of the protein substrate Cdk2-pTpY/CycA provides the critical proton to the leaving group. Phosphates 196-205 cyclin dependent kinase 2 Homo sapiens 231-235 12417722-8 2002 Inhibition of Cdk2 activity was associated with increased binding of p21 and p27 to Cdk2 and decreased phosphorylation of Cdk2 on Thr(160). Threonine 130-133 cyclin dependent kinase 2 Homo sapiens 14-18 12356752-4 2002 Using the natural Cdc25A substrate, Tyr(15)-phosphorylated Cdk2/cyclin A, we demonstrated that NSC 663284 blocked reactivation of Cdk2/cyclin A kinase by Cdc25A catalytic domain in vitro. Tyrosine 36-39 cyclin dependent kinase 2 Homo sapiens 59-63 12356752-4 2002 Using the natural Cdc25A substrate, Tyr(15)-phosphorylated Cdk2/cyclin A, we demonstrated that NSC 663284 blocked reactivation of Cdk2/cyclin A kinase by Cdc25A catalytic domain in vitro. Tyrosine 36-39 cyclin dependent kinase 2 Homo sapiens 130-134 12359725-0 2002 Stimulation of the Raf/MEK/ERK cascade is necessary and sufficient for activation and Thr-160 phosphorylation of a nuclear-targeted CDK2. Threonine 86-89 cyclin dependent kinase 2 Homo sapiens 132-136 12359725-3 2002 Activation of CDK2 requires the removal of two inhibitory phosphates (Thr-14 and Tyr-15) and the addition of one activating phosphate (Thr-160) by a nuclear localized CDK-activating kinase, which is thought to be constitutively active. Phosphates 58-68 cyclin dependent kinase 2 Homo sapiens 14-18 12359725-3 2002 Activation of CDK2 requires the removal of two inhibitory phosphates (Thr-14 and Tyr-15) and the addition of one activating phosphate (Thr-160) by a nuclear localized CDK-activating kinase, which is thought to be constitutively active. Threonine 70-73 cyclin dependent kinase 2 Homo sapiens 14-18 12359725-3 2002 Activation of CDK2 requires the removal of two inhibitory phosphates (Thr-14 and Tyr-15) and the addition of one activating phosphate (Thr-160) by a nuclear localized CDK-activating kinase, which is thought to be constitutively active. Tyrosine 81-84 cyclin dependent kinase 2 Homo sapiens 14-18 12359725-3 2002 Activation of CDK2 requires the removal of two inhibitory phosphates (Thr-14 and Tyr-15) and the addition of one activating phosphate (Thr-160) by a nuclear localized CDK-activating kinase, which is thought to be constitutively active. Phosphates 58-67 cyclin dependent kinase 2 Homo sapiens 14-18 12359725-3 2002 Activation of CDK2 requires the removal of two inhibitory phosphates (Thr-14 and Tyr-15) and the addition of one activating phosphate (Thr-160) by a nuclear localized CDK-activating kinase, which is thought to be constitutively active. Threonine 135-138 cyclin dependent kinase 2 Homo sapiens 14-18 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. U 0126 267-272 cyclin dependent kinase 2 Homo sapiens 32-36 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. U 0126 267-272 cyclin dependent kinase 2 Homo sapiens 45-49 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. U 0126 267-272 cyclin dependent kinase 2 Homo sapiens 45-49 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. Threonine 380-383 cyclin dependent kinase 2 Homo sapiens 32-36 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. Threonine 380-383 cyclin dependent kinase 2 Homo sapiens 45-49 12359725-4 2002 Surprisingly, nuclear localized CDK2-NLS and CDK2-NLS(A14,F15), which lacks the inhibitory phosphorylation sites, require serum to become active, despite complexing with expressed cyclin E. We show that inhibition of mitogen-mediated ERK activation by treatment with U0126, a selective MEK inhibitor, or expression of dominant-negative ERK markedly reduces the phosphorylation of Thr-160 and enzymatic activity of both CDK2-NLS constructs. Threonine 380-383 cyclin dependent kinase 2 Homo sapiens 45-49 12359725-5 2002 Consistent with a role for ERK in Thr-160 phosphorylation, expression of constitutively active Raf-1 induces Thr-160 phosphorylation of CDK2-NLS in serum-arrested cells, an effect that is blocked by treatment with U0126. Threonine 34-37 cyclin dependent kinase 2 Homo sapiens 136-140 12359725-5 2002 Consistent with a role for ERK in Thr-160 phosphorylation, expression of constitutively active Raf-1 induces Thr-160 phosphorylation of CDK2-NLS in serum-arrested cells, an effect that is blocked by treatment with U0126. Threonine 109-112 cyclin dependent kinase 2 Homo sapiens 136-140 12359725-5 2002 Consistent with a role for ERK in Thr-160 phosphorylation, expression of constitutively active Raf-1 induces Thr-160 phosphorylation of CDK2-NLS in serum-arrested cells, an effect that is blocked by treatment with U0126. U 0126 214-219 cyclin dependent kinase 2 Homo sapiens 136-140 12359725-6 2002 Taken together, these data show a new role for ERK in G1 cell cycle progression: In addition to its role in stimulating cyclin D1 expression and nuclear translocation of CDK2, ERK regulates Thr-160 phosphorylation of CDK2-cyclin E. Threonine 190-193 cyclin dependent kinase 2 Homo sapiens 170-174 12359725-6 2002 Taken together, these data show a new role for ERK in G1 cell cycle progression: In addition to its role in stimulating cyclin D1 expression and nuclear translocation of CDK2, ERK regulates Thr-160 phosphorylation of CDK2-cyclin E. Threonine 190-193 cyclin dependent kinase 2 Homo sapiens 217-221 12429981-4 2002 Analysis of the expression of cell cycle-related proteins after the addition of catechin showed that the cyclin-dependent kinase (cdk) 2 and the cdk4 proteins were decreased after administration, the expression of cyclin A protein was increased at 24 h after administration, however, the expression of the cyclin D1 and cyclin E proteins was unchanged. Catechin 80-88 cyclin dependent kinase 2 Homo sapiens 105-136 12505059-8 2002 Phenethyl caffeiate also prevented the phosphorylation of cdk2 and Rb, indicating NF-kappaB was required for G1/S transition. phenethyl caffeiate 0-19 cyclin dependent kinase 2 Homo sapiens 58-62 12379237-5 2002 Hygrolidin-induced p21 bound to and inhibit cyclin A-cdk2 complex more strongly than cyclin E-cdk2 complex. hygrolidin 0-10 cyclin dependent kinase 2 Homo sapiens 53-57 12431050-5 2002 A unique combination of active pharmacophores led us to a series of semicarbazide-based inhibitors that are highly potent against CDK2 and CDK4 while maintaining selectivity against other relevant serine/threonine kinases. carbamylhydrazine 68-81 cyclin dependent kinase 2 Homo sapiens 130-134 12421932-5 2002 The presence of atRA led to elevated levels of cyclin D3, -E, and -A, decreased levels of p27(Kip1), increased activity of cyclin-dependent kinase 2, and enhanced phosphorylation of the retinoblastoma protein (pRB). Tretinoin 16-20 cyclin dependent kinase 2 Homo sapiens 123-148 12431051-3 2002 The identification of indeno[1,2-c]pyrazol-4-ones as inhibitors of cyclin-dependent kinases (CDKs) has led to the discovery of a series of novel and potent compounds. indeno[1,2-c]pyrazol-4-ones 22-49 cyclin dependent kinase 2 Homo sapiens 93-97 12431051-9 2002 An X-ray crystal structure of one of the alkyl compounds, 13q, complexed with CDK2 was determined and showed the inhibitor residing in the adenosine 5"-triphosphate pocket of the enzyme. Adenosine Triphosphate 139-164 cyclin dependent kinase 2 Homo sapiens 78-82 12485874-0 2002 Activation and phosphorylation on Thr-160 of nuclear-targeted CDK2 Is ERK dependent. Threonine 34-37 cyclin dependent kinase 2 Homo sapiens 62-66 12411392-3 2002 In isolated neonatal ventricular myocytes, apoptotic cell death induced by hypoxia (deferoxamine, 100 micro mol/L) specifically activated cyclin-dependent kinases (cdks) 2 and 3. Deferoxamine 84-96 cyclin dependent kinase 2 Homo sapiens 138-177 12379472-4 2002 In MCF-7 cells, leptin and high glucose stimulated cell proliferation as demonstrated by the increases in DNA synthesis and expression of cdk2 and cyclin D1. Glucose 32-39 cyclin dependent kinase 2 Homo sapiens 138-142 12372407-3 2002 The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. Roscovitine 135-146 cyclin dependent kinase 2 Homo sapiens 130-134 12376477-0 2002 Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells. tangeretin 0-10 cyclin dependent kinase 2 Homo sapiens 59-91 12234612-0 2002 SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. SU 9516 0-6 cyclin dependent kinase 2 Homo sapiens 10-35 12234612-4 2002 We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. 3-substituted indolinone 25-49 cyclin dependent kinase 2 Homo sapiens 173-177 12234612-4 2002 We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. SU 9516 60-135 cyclin dependent kinase 2 Homo sapiens 173-177 12234612-9 2002 After a 24-hr treatment with 5 microM SU9516, cyclin D1 and cdk2 levels decreased by 10-60%. SU 9516 38-44 cyclin dependent kinase 2 Homo sapiens 60-64 12234612-10 2002 These findings delineate a previously undescribed mechanism for SU9516-mediated cell growth arrest through down-regulation of cyclin D1, inhibition of cdk2 levels and activity, and pan-sequestration of E2F. SU 9516 64-70 cyclin dependent kinase 2 Homo sapiens 151-155 12372407-2 2002 Roscovitine has been shown to potently inhibit cyclin-dependent kinases 1, 2 and 5 (CDK1, 2, and 5), and the structure of CDK2 complexed with roscovitine has been reported; however, no structural data are available for complexes of CDK5 with inhibitors. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 122-126 12372407-2 2002 Roscovitine has been shown to potently inhibit cyclin-dependent kinases 1, 2 and 5 (CDK1, 2, and 5), and the structure of CDK2 complexed with roscovitine has been reported; however, no structural data are available for complexes of CDK5 with inhibitors. Roscovitine 142-153 cyclin dependent kinase 2 Homo sapiens 122-126 12372407-3 2002 The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. Roscovitine 36-47 cyclin dependent kinase 2 Homo sapiens 130-134 12372407-3 2002 The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. Adenosine Triphosphate 70-73 cyclin dependent kinase 2 Homo sapiens 130-134 12470513-4 2002 H(2)O(2) (100 microM) blocked serum-stimulated cyclin-dependent kinase-2 (CDK2) activity, but not CDK4 activity, suggesting that cell cycle arrest occurred in part by inhibiting CDK2 activity. Hydrogen Peroxide 0-8 cyclin dependent kinase 2 Homo sapiens 47-72 12470513-4 2002 H(2)O(2) (100 microM) blocked serum-stimulated cyclin-dependent kinase-2 (CDK2) activity, but not CDK4 activity, suggesting that cell cycle arrest occurred in part by inhibiting CDK2 activity. Hydrogen Peroxide 0-8 cyclin dependent kinase 2 Homo sapiens 74-78 12470513-4 2002 H(2)O(2) (100 microM) blocked serum-stimulated cyclin-dependent kinase-2 (CDK2) activity, but not CDK4 activity, suggesting that cell cycle arrest occurred in part by inhibiting CDK2 activity. Hydrogen Peroxide 0-8 cyclin dependent kinase 2 Homo sapiens 178-182 12376477-5 2002 Immunocomplex kinase experiments showed that tangeretin inhibited the activities of cyclin-dependent kinases 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. tangeretin 45-55 cyclin dependent kinase 2 Homo sapiens 84-110 12376477-5 2002 Immunocomplex kinase experiments showed that tangeretin inhibited the activities of cyclin-dependent kinases 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. tangeretin 45-55 cyclin dependent kinase 2 Homo sapiens 112-116 12376477-6 2002 As the cells were exposed to tangeretin (50 microM) over 48 h a gradual loss of both Cdk2 and 4 kinase activities occurred. tangeretin 29-39 cyclin dependent kinase 2 Homo sapiens 85-89 12376477-8 2002 In addition, tangeretin also increased the level of the Cdk inhibitor p27 protein within 18 h. These results suggest that tangeretin either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins, such as Cdk2 and Cdk4, or mediates the increase of Cdk inhibitors p21 and p27. tangeretin 13-23 cyclin dependent kinase 2 Homo sapiens 261-265 12376477-8 2002 In addition, tangeretin also increased the level of the Cdk inhibitor p27 protein within 18 h. These results suggest that tangeretin either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins, such as Cdk2 and Cdk4, or mediates the increase of Cdk inhibitors p21 and p27. tangeretin 122-132 cyclin dependent kinase 2 Homo sapiens 261-265 12354066-1 2002 This article presents a molecular dynamics (MD) study of the cdk2 enzyme and its two complexes with the inhibitors isopentenyladenine and roscovitine using the Cornell et al. N(6)-(delta(2)-isopentenyl)adenine 115-133 cyclin dependent kinase 2 Homo sapiens 61-65 12354066-1 2002 This article presents a molecular dynamics (MD) study of the cdk2 enzyme and its two complexes with the inhibitors isopentenyladenine and roscovitine using the Cornell et al. Roscovitine 138-149 cyclin dependent kinase 2 Homo sapiens 61-65 12354066-11 2002 The results support the idea that the isopentenyladenine binding mode can be used for cdk2 inhibitors design and that all possibilities to improve this binding mode were not uncovered yet. N(6)-(delta(2)-isopentenyl)adenine 38-56 cyclin dependent kinase 2 Homo sapiens 86-90 12204894-5 2002 Using Western blot analysis and in vitro kinase assays, we found that dexamethasone results in decreased activity of CDK2 and 4, decreased levels of cyclin D, E2F, and Myc, and increased levels of the CDK inhibitor p21(Cip1). Dexamethasone 70-83 cyclin dependent kinase 2 Homo sapiens 117-127 12490153-3 2002 The kinase activity of cdk2, cdk4, and cdk6 was significantly reduced and hypophosphorylation of pRb on serine 795 (S795) and threonine 373 (T373) was observed. Serine 104-110 cyclin dependent kinase 2 Homo sapiens 23-27 12490153-3 2002 The kinase activity of cdk2, cdk4, and cdk6 was significantly reduced and hypophosphorylation of pRb on serine 795 (S795) and threonine 373 (T373) was observed. Threonine 126-135 cyclin dependent kinase 2 Homo sapiens 23-27 12182847-0 2002 Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: structural variants of the C-terminal Phe. Phenylalanine 115-118 cyclin dependent kinase 2 Homo sapiens 22-26 12182847-2 2002 Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. beta-hydroxyphenylalanine 45-62 cyclin dependent kinase 2 Homo sapiens 210-214 12182847-2 2002 Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. 5,7-diacetamido-3,5,7,9-tetradeoxynonulosonic acid 64-67 cyclin dependent kinase 2 Homo sapiens 210-214 12182847-2 2002 Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. (2s)-phenylalaninol 73-92 cyclin dependent kinase 2 Homo sapiens 210-214 12244298-2 2002 Iterative structure-based design was used to optimize the ATP- competitive inhibition of CDK1 and CDK2 by O(6)-cyclohexylmethylguanines, resulting in O(6)-cyclohexylmethyl-2-(4"- sulfamoylanilino)purine. Adenosine Triphosphate 58-61 cyclin dependent kinase 2 Homo sapiens 98-102 12244298-2 2002 Iterative structure-based design was used to optimize the ATP- competitive inhibition of CDK1 and CDK2 by O(6)-cyclohexylmethylguanines, resulting in O(6)-cyclohexylmethyl-2-(4"- sulfamoylanilino)purine. NU2058 106-135 cyclin dependent kinase 2 Homo sapiens 98-102 12244298-2 2002 Iterative structure-based design was used to optimize the ATP- competitive inhibition of CDK1 and CDK2 by O(6)-cyclohexylmethylguanines, resulting in O(6)-cyclohexylmethyl-2-(4"- sulfamoylanilino)purine. o(6)-cyclohexylmethyl-2-(4"- sulfamoylanilino)purine 150-202 cyclin dependent kinase 2 Homo sapiens 98-102 12244298-3 2002 The new inhibitor is 1,000-fold more potent than the parent compound (K(i) values for CDK1 = 9 nM and CDK2 = 6 nM versus 5,000 nM and 12,000 nM, respectively, for O(6)-cyclohexylmethylguanine). NU2058 163-191 cyclin dependent kinase 2 Homo sapiens 102-106 12244298-4 2002 The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Hydrogen 76-84 cyclin dependent kinase 2 Homo sapiens 127-131 12244298-4 2002 The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Hydrogen 76-84 cyclin dependent kinase 2 Homo sapiens 231-235 12244298-4 2002 The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Aspartic Acid 117-120 cyclin dependent kinase 2 Homo sapiens 127-131 12244298-4 2002 The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Aspartic Acid 117-120 cyclin dependent kinase 2 Homo sapiens 231-235 12114499-5 2002 Tat-mediated CTD phosphorylation by CDK2 required cysteine 22 in the activation domain of Tat and amino acids 42-72 of Tat. Cysteine 50-58 cyclin dependent kinase 2 Homo sapiens 36-40 12529993-12 2002 CD437 (1 microM) induced activity of cdk2- and p34cdc2-associated H1 kinase by 14.6- and 1.8-fold, respectively, in SC-M1 cells. CD 437 0-5 cyclin dependent kinase 2 Homo sapiens 37-41 12529993-13 2002 In contrast, CD437 slightly increased (1.6-fold) the cdk2-associated H1 kinase activity in AGS cells. CD 437 13-18 cyclin dependent kinase 2 Homo sapiens 53-57 12181445-0 2002 Inhibition of cyclin-dependent kinase 2 by the Chk1-Cdc25A pathway during the S-phase checkpoint activated by fludarabine: dysregulation by 7-hydroxystaurosporine. fludarabine 110-121 cyclin dependent kinase 2 Homo sapiens 14-39 12181445-0 2002 Inhibition of cyclin-dependent kinase 2 by the Chk1-Cdc25A pathway during the S-phase checkpoint activated by fludarabine: dysregulation by 7-hydroxystaurosporine. 7-hydroxystaurosporine 140-162 cyclin dependent kinase 2 Homo sapiens 14-39 12181445-1 2002 Human myeloid leukemia ML-1 cells responded to cytostatic concentrations of fludarabine nucleoside (F-ara-A) by instituting an arrest in S-phase that involved the inhibition of cyclin-dependent kinase 2 (Cdk2). fludarabine nucleoside 76-98 cyclin dependent kinase 2 Homo sapiens 177-202 12181445-1 2002 Human myeloid leukemia ML-1 cells responded to cytostatic concentrations of fludarabine nucleoside (F-ara-A) by instituting an arrest in S-phase that involved the inhibition of cyclin-dependent kinase 2 (Cdk2). fludarabine nucleoside 76-98 cyclin dependent kinase 2 Homo sapiens 204-208 12181445-1 2002 Human myeloid leukemia ML-1 cells responded to cytostatic concentrations of fludarabine nucleoside (F-ara-A) by instituting an arrest in S-phase that involved the inhibition of cyclin-dependent kinase 2 (Cdk2). fludarabine 100-107 cyclin dependent kinase 2 Homo sapiens 177-202 12181445-1 2002 Human myeloid leukemia ML-1 cells responded to cytostatic concentrations of fludarabine nucleoside (F-ara-A) by instituting an arrest in S-phase that involved the inhibition of cyclin-dependent kinase 2 (Cdk2). fludarabine 100-107 cyclin dependent kinase 2 Homo sapiens 204-208 12181445-2 2002 This seemed to be mediated by 1) persistent phosphorylation on the Tyr(15) residue of Cdk2 and 2) an increased association of Cdk2 with p21. Tyrosine 67-70 cyclin dependent kinase 2 Homo sapiens 86-96 12181445-2 2002 This seemed to be mediated by 1) persistent phosphorylation on the Tyr(15) residue of Cdk2 and 2) an increased association of Cdk2 with p21. Tyrosine 67-70 cyclin dependent kinase 2 Homo sapiens 86-90 12181445-7 2002 Under these conditions, the kinase activity of Chk1 was reduced, Cdc25A phosphatase activity was increased, the level of Tyr(15) phosphorylation of Cdk2 was reduced, and the kinase activity associated with immunoprecipitates of Cdk2 and cyclin A was reactivated. Tyrosine 121-124 cyclin dependent kinase 2 Homo sapiens 148-152 12181445-10 2002 Thus, the DNA damage induced by F-ara-A initiated a hierarchical regulatory cascade through Chk1 and Cdc25A that resulted in Cdk2 inhibition, affecting an S-phase checkpoint that was dysregulated by UCN-01. fludarabine 32-39 cyclin dependent kinase 2 Homo sapiens 125-129 12139449-1 2002 O(6)-substituted guanines are adenosine 5"-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Adenosine Triphosphate 57-60 cyclin dependent kinase 2 Homo sapiens 107-111 12119558-6 2002 During this inhibition process, resveratrol increases the content of cyclins A and B1 as well as cyclin-dependent kinases Cdk1 and Cdk2. Resveratrol 32-43 cyclin dependent kinase 2 Homo sapiens 131-135 12139449-1 2002 O(6)-substituted guanines are adenosine 5"-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Ribose 164-170 cyclin dependent kinase 2 Homo sapiens 107-111 12139449-1 2002 O(6)-substituted guanines are adenosine 5"-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. (6)-substituted 1-16 cyclin dependent kinase 2 Homo sapiens 107-111 12139449-1 2002 O(6)-substituted guanines are adenosine 5"-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Guanine 17-25 cyclin dependent kinase 2 Homo sapiens 107-111 12139449-2 2002 Fifty-eight O(6)-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. o(6)-substituted guanines 12-37 cyclin dependent kinase 2 Homo sapiens 151-155 12139449-1 2002 O(6)-substituted guanines are adenosine 5"-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. Adenosine Triphosphate 30-55 cyclin dependent kinase 2 Homo sapiens 107-111 12175534-4 2002 Analysis of G1 cell cycle regulators expression revealed that monoterpenes increased expression of cdk inhibitor p21(Waf1/Cip1) and cyclin E, and decreased expression of cyclin D1, cyclin-dependent kinase (cdk) 4 and cdk2. Monoterpenes 62-74 cyclin dependent kinase 2 Homo sapiens 217-221 12096339-6 2002 The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Tamoxifen 170-179 cyclin dependent kinase 2 Homo sapiens 23-27 12124352-6 2002 Treatment with either Herceptin or the PI3K inhibitor LY294002 increased the levels of p27 in the nucleus>cytosol, thus increasing the ratio of p27:Cdk2 in the nucleus and inhibiting Cdk2 activity and cell proliferation. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 54-62 cyclin dependent kinase 2 Homo sapiens 151-155 12124352-6 2002 Treatment with either Herceptin or the PI3K inhibitor LY294002 increased the levels of p27 in the nucleus>cytosol, thus increasing the ratio of p27:Cdk2 in the nucleus and inhibiting Cdk2 activity and cell proliferation. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 54-62 cyclin dependent kinase 2 Homo sapiens 186-190 12063555-2 2002 Roscovitine, [2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine], is a potent and selective inhibitor of the Cdk2 and Cdc2. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 127-131 12081504-3 2002 Interaction of CDK2 with cyclin A results in a partially active complex that is moderately defective in the binding of the protein substrate, but not ATP, and severely defective in both phosphoryl group transfer and turnover. Adenosine Triphosphate 150-153 cyclin dependent kinase 2 Homo sapiens 15-19 12081504-6 2002 Our data support a model for the activation of CDK2 in vivo, in which interaction of unphosphorylated CDK2 with cyclin A serves to configure the active site for ground-state binding of both ATP and the protein substrate, and further aligns ATP in the transition state for phosphoryl transfer. Adenosine Triphosphate 190-193 cyclin dependent kinase 2 Homo sapiens 47-51 12081504-6 2002 Our data support a model for the activation of CDK2 in vivo, in which interaction of unphosphorylated CDK2 with cyclin A serves to configure the active site for ground-state binding of both ATP and the protein substrate, and further aligns ATP in the transition state for phosphoryl transfer. Adenosine Triphosphate 190-193 cyclin dependent kinase 2 Homo sapiens 102-106 12081504-6 2002 Our data support a model for the activation of CDK2 in vivo, in which interaction of unphosphorylated CDK2 with cyclin A serves to configure the active site for ground-state binding of both ATP and the protein substrate, and further aligns ATP in the transition state for phosphoryl transfer. Adenosine Triphosphate 240-243 cyclin dependent kinase 2 Homo sapiens 47-51 12081504-6 2002 Our data support a model for the activation of CDK2 in vivo, in which interaction of unphosphorylated CDK2 with cyclin A serves to configure the active site for ground-state binding of both ATP and the protein substrate, and further aligns ATP in the transition state for phosphoryl transfer. Adenosine Triphosphate 240-243 cyclin dependent kinase 2 Homo sapiens 102-106 12063555-4 2002 Roscovitine was found to inhibit the growth of all 11 HNSCC cell lines in time- and dose-dependent manner and to diminish the Cdk2 and Cdc2 activities. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 126-130 12063555-2 2002 Roscovitine, [2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine], is a potent and selective inhibitor of the Cdk2 and Cdc2. Roscovitine 13-81 cyclin dependent kinase 2 Homo sapiens 127-131 12012012-6 2002 The CDDP-induced S-phase accumulation of OVCCR1 cells resulted from an activation of CDK2/cyclin A activity. cddp 4-8 cyclin dependent kinase 2 Homo sapiens 85-89 11959850-5 2002 The first step involves the rapid association between the PSTAIRE helix of Cdk2 and helices 3 and 5 of the cyclin to yield an intermediate complex in which the threonine in the T-loop is not accessible for phosphorylation. Threonine 160-169 cyclin dependent kinase 2 Homo sapiens 75-79 12044161-0 2002 Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state analogue: implications for the protein kinase mechanism. Nitrates 53-60 cyclin dependent kinase 2 Homo sapiens 30-34 12044161-2 2002 The catalytic mechanism of phospho-CDK2/cyclin A (pCDK2/cyclin A) has been probed with structural and kinetic studies using the trigonal NO(3)(-) ion, which can be viewed as a mimic of the metaphosphate transition state. metaphosphate 189-202 cyclin dependent kinase 2 Homo sapiens 35-39 12044161-6 2002 Kinetic studies demonstrate that nitrate is not an effective inhibitor of protein kinases, consistent with the structural results that show the nitrate ion makes few stabilizing interactions with CDK2 at the catalytic site. Nitrates 144-151 cyclin dependent kinase 2 Homo sapiens 196-200 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. Tretinoin 26-30 cyclin dependent kinase 2 Homo sapiens 84-88 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. Tretinoin 26-30 cyclin dependent kinase 2 Homo sapiens 84-87 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. cddp 57-61 cyclin dependent kinase 2 Homo sapiens 84-88 12012012-7 2002 Our results indicate that ATRA-pretreatment modified the CDDP-induced regulation of CDK2 activity by the CDK inhibitors p21 and p27. cddp 57-61 cyclin dependent kinase 2 Homo sapiens 84-87 12012012-8 2002 Taken together, our findings suggest that ATRA potentiates the apoptosis induced by CDDP in ovarian carcinoma cells and that this action is sustained by modulation of the activity of CDK2/cyclin A. Tretinoin 42-46 cyclin dependent kinase 2 Homo sapiens 183-187 12112322-1 2002 Treatment of MCF 7 cells with the fungal estrogen zearalenone induced cyclin E-associated kinase activity transiently within 9-12 h; total cyclin-dependent kinase (Cdk) 2 activity was elevated for 24 h and beyond. Zearalenone 50-61 cyclin dependent kinase 2 Homo sapiens 139-170 12053219-2 2002 Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. epigallocatechin gallate 0-26 cyclin dependent kinase 2 Homo sapiens 127-131 12053219-2 2002 Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. epigallocatechin gallate 28-32 cyclin dependent kinase 2 Homo sapiens 127-131 12053219-2 2002 Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. Polyphenols 54-64 cyclin dependent kinase 2 Homo sapiens 127-131 12053219-3 2002 This suggests that EGCG may exert its growth-inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. epigallocatechin gallate 19-23 cyclin dependent kinase 2 Homo sapiens 117-121 12432276-6 2002 Further, treatment of the human glioma cell line A-172 with rolipram results in increased expression of the cell cycle inhibitors p21(Cip1) and p27(KiP1), and decreased activity of cdk2, a cyclin-dependent kinase essential for cell cycle progression. Rolipram 60-68 cyclin dependent kinase 2 Homo sapiens 181-185 11919196-4 2002 Cyclin E plays a crucial role in the cell cycle by activating cyclin-dependent kinase 2, which phosphorylates Rb, leading to progression from G(1) into S phase. Rubidium 110-112 cyclin dependent kinase 2 Homo sapiens 62-87 12112322-4 2002 The activity of cyclin E/Cdk2 complexes from zearalenone-treated lysates was inhibited in vitro by recombinant p27(KIP1), and this inhibition was relieved by the addition of recombinant cyclin D1/Cdk4 complexes. Zearalenone 45-56 cyclin dependent kinase 2 Homo sapiens 25-29 12479270-15 2002 Silibinin-treated cells showed up to 2.4- and 3.6-fold increases in Cip1/p21 and Kip1/p27 levels, respectively, and a decrease in CDK2 (80%), CDK4 (98%), and cyclin D1 (60%). Silybin 0-9 cyclin dependent kinase 2 Homo sapiens 130-134 11836565-4 2002 TGF-beta1 intensified the decreased expression of CDK2, CDK4, CDK6 and cyclin D1 in EB1089-treated NCI-H929 cells. seocalcitol 84-90 cyclin dependent kinase 2 Homo sapiens 50-54 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. Carbolines 11-26 cyclin dependent kinase 2 Homo sapiens 37-41 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. Carbolines 11-26 cyclin dependent kinase 2 Homo sapiens 100-104 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. 1-(2-chlorophenyl)- 121-140 cyclin dependent kinase 2 Homo sapiens 100-104 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. 1-(2-fluorophenyl)- 147-166 cyclin dependent kinase 2 Homo sapiens 100-104 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. 1-(2-chloro-5-nitrophenyl)- 177-204 cyclin dependent kinase 2 Homo sapiens 100-104 11909733-3 2002 While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines. Carbolines 210-225 cyclin dependent kinase 2 Homo sapiens 100-104 12429923-6 2002 Silibinin treatment also resulted in 90 and 70% decrease in CDK4 and CDK2 levels, respectively, but did not alter the protein levels of cyclin D1 and cyclin E. Consistent with its effect on G1 cell cycle regulators, silibinin treated cells exhibited a strong G1 arrest, almost complete growth inhibition, and morphological changes suggestive of differentiation. Silybin 0-9 cyclin dependent kinase 2 Homo sapiens 69-73 12054639-4 2002 This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. Adenosine Triphosphate 73-76 cyclin dependent kinase 2 Homo sapiens 145-149 12054639-4 2002 This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. alvocidib 150-162 cyclin dependent kinase 2 Homo sapiens 145-149 12054639-4 2002 This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. alvocidib 249-261 cyclin dependent kinase 2 Homo sapiens 145-149 11914144-11 2002 No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations. Aminolevulinic Acid 81-84 cyclin dependent kinase 2 Homo sapiens 95-99 11914144-11 2002 No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations. Aminolevulinic Acid 143-146 cyclin dependent kinase 2 Homo sapiens 95-99 12191604-5 2002 We have determined the crystal structures of staurosporine bound to monomeric CDK2 and UCN-01 bound to active phospho-CDK2/cyclin A. Staurosporine 45-58 cyclin dependent kinase 2 Homo sapiens 78-82 11792416-7 2002 Although, flavopiridol did not affect cyclin D1 and cyclin A levels, it inhibited Mcl-1 and Bcl-2 protein levels and cyclin-dependent kinase 2 activity. alvocidib 10-22 cyclin dependent kinase 2 Homo sapiens 117-142 11805301-5 2002 In MDA-231 cells, cAMP elevation results in sustained expression of the cell cycle inhibitor p27kip1 and inhibition of CDK2 activity, whereas in MDA-435 cells inhibition of mitogen-activated protein (MAP) kinase 1,2 activity is observed. Cyclic AMP 18-22 cyclin dependent kinase 2 Homo sapiens 119-123 11835680-5 2002 CDK2 activity was suppressed by caffeine, whereas activity of CDC2 was enhanced by suppressing phosphorylation on Tyr15 and by interfering with 14-3-3 binding to CDC25C. Caffeine 32-40 cyclin dependent kinase 2 Homo sapiens 0-4 12191604-5 2002 We have determined the crystal structures of staurosporine bound to monomeric CDK2 and UCN-01 bound to active phospho-CDK2/cyclin A. Staurosporine 45-58 cyclin dependent kinase 2 Homo sapiens 118-122 12191604-5 2002 We have determined the crystal structures of staurosporine bound to monomeric CDK2 and UCN-01 bound to active phospho-CDK2/cyclin A. 7-hydroxystaurosporine 87-93 cyclin dependent kinase 2 Homo sapiens 118-122 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. Adenosine Triphosphate 18-21 cyclin dependent kinase 2 Homo sapiens 38-42 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. Adenosine Triphosphate 18-21 cyclin dependent kinase 2 Homo sapiens 181-185 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. Serine 192-198 cyclin dependent kinase 2 Homo sapiens 38-42 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. Serine 192-198 cyclin dependent kinase 2 Homo sapiens 181-185 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. 7-hydroxystaurosporine 118-124 cyclin dependent kinase 2 Homo sapiens 38-42 12191604-8 2002 Comparison of the ATP-binding site of CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine in Chk1, thus providing a possible explanation for the effectiveness of UCN-01 against this kinase. 7-hydroxystaurosporine 118-124 cyclin dependent kinase 2 Homo sapiens 181-185 12191604-9 2002 For cells to exit mitosis, the CDKs must be completely inactivated, firstly by the ubiquintin-mediated destruction of the cyclins, followed by dephosphorylation of phospho-Thr160 (in CDK2) catalysed by the kinase-associated phosphatase and protein phosphatase 2C. ubiquintin 83-93 cyclin dependent kinase 2 Homo sapiens 31-35 12191605-5 2002 Knowledge of the structure of CDK2 has been key in driving the design and development of a large number of ATP competitive inhibitors. Adenosine Triphosphate 107-110 cyclin dependent kinase 2 Homo sapiens 30-34 12191605-6 2002 Crystallography has revealed that the ATP-binding site of CDK2 can accommodate a number of diverse molecular frameworks, exploiting various sites of interaction. Adenosine Triphosphate 38-41 cyclin dependent kinase 2 Homo sapiens 58-62 11755359-1 2002 A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. 5-aryl-1h-pyrazole 2-20 cyclin dependent kinase 2 Homo sapiens 87-112 11755359-1 2002 A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. 5-aryl-1h-pyrazole 2-20 cyclin dependent kinase 2 Homo sapiens 114-118 11755359-1 2002 A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. Adenosine Triphosphate 67-70 cyclin dependent kinase 2 Homo sapiens 87-112 11755359-1 2002 A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. Adenosine Triphosphate 67-70 cyclin dependent kinase 2 Homo sapiens 114-118 11807175-5 2002 Good selectivity among these ATP competitive inhibitors for cdks over other kinases has been established, and selectivity between individual cdks is often observed. Adenosine Triphosphate 29-32 cyclin dependent kinase 2 Homo sapiens 60-64 12643444-8 2002 After labeling of CDK2 and RB1, hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells. Asbestos 91-99 cyclin dependent kinase 2 Homo sapiens 18-22 11604388-5 2001 To determine the kinetic mechanism of cdk2.GST-cyclin E and cdk5.GST-p25, kinase activity was measured in experiments in which concentrations of peptide and ATP substrates were varied in the presence of dead-end inhibitors. Adenosine Triphosphate 157-160 cyclin dependent kinase 2 Homo sapiens 38-42 11756234-9 2002 In addition, POH treatment induces an increased association of p21(WAF1) with cyclin E-Cdk2 complexes, and inhibits the activating phosphorylation of Cdk2. perillyl alcohol 13-16 cyclin dependent kinase 2 Homo sapiens 87-91 11756234-9 2002 In addition, POH treatment induces an increased association of p21(WAF1) with cyclin E-Cdk2 complexes, and inhibits the activating phosphorylation of Cdk2. perillyl alcohol 13-16 cyclin dependent kinase 2 Homo sapiens 150-154 12200855-7 2002 Finally, the Western blotting results verified that the levels of protein expression of CDK2, cyclin A and cyclin E were relatively high in alpha 1H transfectants compared to control cultures. Hydrogen 146-148 cyclin dependent kinase 2 Homo sapiens 88-92 11604388-7 2001 An aminopyrimidine, PNU 112455A, was identified in a screen for inhibitors of cdk2. 2-aminopyrimidine 3-18 cyclin dependent kinase 2 Homo sapiens 78-82 11604388-7 2001 An aminopyrimidine, PNU 112455A, was identified in a screen for inhibitors of cdk2. PNU 112455A 20-31 cyclin dependent kinase 2 Homo sapiens 78-82 11604388-9 2001 In addition, a co-crystal of PNU 112455A with cdk2 showed that the inhibitor binds in the ATP binding pocket of the enzyme. Adenosine Triphosphate 90-93 cyclin dependent kinase 2 Homo sapiens 46-50 11604388-12 2001 For cdk2.GST-cyclin E the kinetic parameters were determined to be K(m, ATP) = 3.6 +/- 1.0 microm, K(m, peptide) = 4.6 +/- 1.4 microm, and the anticooperativity factor, alpha = 130 +/- 44. Adenosine Triphosphate 72-75 cyclin dependent kinase 2 Homo sapiens 4-8 11728181-0 2001 Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. 2-oxindole 0-8 cyclin dependent kinase 2 Homo sapiens 29-54 11741479-5 2001 By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N"-pyridin-2-ylurea 15 (IC(50) = 0.10 microM), together with preliminary SAR. Adenosine Triphosphate 108-111 cyclin dependent kinase 2 Homo sapiens 86-89 11741479-5 2001 By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N"-pyridin-2-ylurea 15 (IC(50) = 0.10 microM), together with preliminary SAR. n-(9-oxo-9h-fluoren-4-yl)-n"-pyridin-2-ylurea 15 195-243 cyclin dependent kinase 2 Homo sapiens 86-89 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 3-(anilinomethylene)-1,3-dihydro-2h-indol-2-ones 100-148 cyclin dependent kinase 2 Homo sapiens 208-212 11728181-0 2001 Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. 2-oxindole 0-8 cyclin dependent kinase 2 Homo sapiens 56-60 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 2-oxindole 31-39 cyclin dependent kinase 2 Homo sapiens 181-206 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 2-oxindole 31-39 cyclin dependent kinase 2 Homo sapiens 208-212 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 1h-indole-2,3-dione 3-phenylhydrazones 57-95 cyclin dependent kinase 2 Homo sapiens 181-206 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 1h-indole-2,3-dione 3-phenylhydrazones 57-95 cyclin dependent kinase 2 Homo sapiens 208-212 11728181-1 2001 Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). 3-(anilinomethylene)-1,3-dihydro-2h-indol-2-ones 100-148 cyclin dependent kinase 2 Homo sapiens 181-206 11746695-3 2001 The protein 3D structure was homology modeled, based on the known crystal structure of CDK2, and new nonbonded parameters for the Mg(2+) coordination complex were developed by means of ab initio quantum chemical calculations. magnesium ion 130-136 cyclin dependent kinase 2 Homo sapiens 87-91 11753686-6 2001 These studies demonstrated that both atRA and BMS453 induce Rb hypophosphorylation and decrease CDK2 kinase activity. Tretinoin 37-41 cyclin dependent kinase 2 Homo sapiens 96-100 11738041-4 2001 RESULTS: Structures of uncomplexed Tyr216 phosphorylated GSK-3beta and of its complex with a peptide and a sulfate ion both show the activation loop adopting a conformation similar to that in the phosphorylated and active forms of the related kinases CDK2 and ERK2. Sulfates 107-114 cyclin dependent kinase 2 Homo sapiens 251-255 11581254-4 2001 However, we now show that some E(2)-induced cyclin E.Cdk2 activation occurs in the absence of increased cyclin D1 levels and requires decreased p21 protein synthesis. Estradiol 31-35 cyclin dependent kinase 2 Homo sapiens 53-57 11581254-6 2001 E(2)-induced activation of cyclin E.Cdk2 is mimicked by targeted inhibition of nascent p21 expression by antisense p21 oligonucleotides. Oligonucleotides 119-135 cyclin dependent kinase 2 Homo sapiens 36-40 11581254-7 2001 Cyclin E.Cdk2 activation is completely inhibited by a combination of antisense cyclin D1 oligonucleotide transfection and elimination of the decrease in nascent p21 by infection with adenoviral-p21. Oligonucleotides 89-104 cyclin dependent kinase 2 Homo sapiens 9-13 11753676-6 2001 Also, RA treatment increased expression of the cdk inhibitor p27 and decreased activity of cdk 2, cdk 4 and cdk 6. Tretinoin 6-8 cyclin dependent kinase 2 Homo sapiens 91-96 11753686-6 2001 These studies demonstrated that both atRA and BMS453 induce Rb hypophosphorylation and decrease CDK2 kinase activity. BMS453 46-52 cyclin dependent kinase 2 Homo sapiens 96-100 11557753-4 2001 It has been previously shown that sanglifehrin A specifically blocks T cell proliferation in response to interleukin 2 by inhibiting the appearance of cell cycle kinase activity cyclinE-Cdk2. sanglifehrin A 34-48 cyclin dependent kinase 2 Homo sapiens 186-190 11557753-6 2001 We report that sanglifehrin A is capable of activating the tumor suppressor gene p53 at the transcription level, leading to up-regulation of p21 that then binds and inhibits the cylcinE-Cdk2 complex. sanglifehrin A 15-29 cyclin dependent kinase 2 Homo sapiens 186-190 11504716-5 2001 We determined one site of phosphorylation by cyclin A-CDK2 at the C terminus of MEF, using mass-spectrometry; mutation of three serine or threonine residues in this region significantly reduced phosphorylation of MEF by cyclin A and reduced cyclin A-mediated suppression of its transactivating activity. Serine 128-134 cyclin dependent kinase 2 Homo sapiens 54-58 11698641-3 2001 After G(1) progression UBF is phosphorylated at serine 388 by cdk2/cyclin E and cdk2/cyclin A. Serine 48-54 cyclin dependent kinase 2 Homo sapiens 62-66 11709727-7 2001 Furthermore, treatment with LY294002 resulted in the selective increase of cyclin-dependent kinase inhibitors p21(Cip1) or p27(Kip1) and suppression of cyclin E-associated Cdk2 kinase activity in ErbB2-overexpressing lines, which may account for their hypersensitivity toward inhibitors of the PI3K pathway in anchorage-independent growth. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 28-36 cyclin dependent kinase 2 Homo sapiens 172-176 11504716-5 2001 We determined one site of phosphorylation by cyclin A-CDK2 at the C terminus of MEF, using mass-spectrometry; mutation of three serine or threonine residues in this region significantly reduced phosphorylation of MEF by cyclin A and reduced cyclin A-mediated suppression of its transactivating activity. Threonine 138-147 cyclin dependent kinase 2 Homo sapiens 54-58 11585773-0 2001 Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers. Tyrosine 21-29 cyclin dependent kinase 2 Homo sapiens 16-20 11676482-3 2001 Earlier, we have shown that resveratrol treatment results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclin (E, D1, and D2) and cyclin-dependent kinases (cdk2, cdk4, and cdk6), results in a G0/G1-phase arrest followed by apoptosis of A431 human epidermoid carcinoma cells (Ahmad et al., Clin. Resveratrol 28-39 cyclin dependent kinase 2 Homo sapiens 193-197 11705886-4 2001 At concentrations < or =0.6 microM (low effective concentrations), DACH-acetato-Pt specifically induced G(1) phase arrest by selectively inhibiting cyclin-dependent kinase 4 (Cdk4) and Cdk2 activities. (diaminocyclohexane)(diacetato)(dichloro)platinum 70-85 cyclin dependent kinase 2 Homo sapiens 188-192 11745413-0 2001 Antitumor action of the PKC activator gnidimacrin through cdk2 inhibition. gnidimacrin 38-49 cyclin dependent kinase 2 Homo sapiens 58-62 11745413-3 2001 In sensitive human leukemia K562 cells, gnidimacrin is a PKC activator that arrests the cell cycle in the G(1) phase by inhibiting cdk2 activity. gnidimacrin 40-51 cyclin dependent kinase 2 Homo sapiens 131-135 11745413-5 2001 Expression of cdc25A, a phosphatase that activates cdk2, was reduced during 24-hr exposure to gnidimacrin. gnidimacrin 94-105 cyclin dependent kinase 2 Homo sapiens 51-55 11745413-6 2001 Moreover, the suppression corresponded in a concentration- and time-dependent manner to both the inhibition of cdk2 activity and the mobility shift observed when cdk2 was electrophoresed on SDS-PAGE, indicating that the phosphorylation state of cdk2 must change. Sodium Dodecyl Sulfate 190-193 cyclin dependent kinase 2 Homo sapiens 162-166 11745413-6 2001 Moreover, the suppression corresponded in a concentration- and time-dependent manner to both the inhibition of cdk2 activity and the mobility shift observed when cdk2 was electrophoresed on SDS-PAGE, indicating that the phosphorylation state of cdk2 must change. Sodium Dodecyl Sulfate 190-193 cyclin dependent kinase 2 Homo sapiens 162-166 11745413-8 2001 These results suggest that gnidimacrin exerts antitumor activity through suppression of cdc25A and inhibition of cdk2 activity. gnidimacrin 27-38 cyclin dependent kinase 2 Homo sapiens 113-117 11687964-9 2001 Since cyclin-dependent kinase 2 (CDK2) triggers initiation of centrosome duplication, and p53 is phosphorylated on Ser 315 by CDK2, we examined the p53 mutants with a replacement of Ser 315 to Ala (A) and Asp (D), both of which retain the transactivation function. Serine 115-118 cyclin dependent kinase 2 Homo sapiens 126-130 11502743-6 2001 Importantly, rather than inhibiting it, Cyclin A-Cdk2 stimulated the initiation activity of pol-prim containing a triple N-terminal alanine mutant of the p180 subunit. Alanine 132-139 cyclin dependent kinase 2 Homo sapiens 49-53 11591175-0 2001 p21(WAF1) is associated with CDK2 and CDK4 protein during HL-60 cell differentiation by TPA treatment. Tetradecanoylphorbol Acetate 88-91 cyclin dependent kinase 2 Homo sapiens 29-33 11524422-7 2001 Phosphorylation of Tyr(185) in ERK2 and association of cyclinA with cdk2 both serve to stabilize ATP binding. Adenosine Triphosphate 97-100 cyclin dependent kinase 2 Homo sapiens 68-72 11822171-4 2001 Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] 28-108 cyclin dependent kinase 2 Homo sapiens 147-151 11822171-4 2001 Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. 4h 110-112 cyclin dependent kinase 2 Homo sapiens 147-151 11822171-4 2001 Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. Roscovitine 238-249 cyclin dependent kinase 2 Homo sapiens 147-151 11676600-1 2001 The cyclin-dependent kinase-activating kinase (CAK) catalyzes the phosphorylation of the cyclin-dependent protein kinases (CDKs) on a threonine residue (Thr160 in human CDK2). Threonine 134-143 cyclin dependent kinase 2 Homo sapiens 123-127 11676600-1 2001 The cyclin-dependent kinase-activating kinase (CAK) catalyzes the phosphorylation of the cyclin-dependent protein kinases (CDKs) on a threonine residue (Thr160 in human CDK2). Threonine 134-143 cyclin dependent kinase 2 Homo sapiens 169-173 11585773-6 2001 Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1 protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase activity. Tyrosine 21-29 cyclin dependent kinase 2 Homo sapiens 16-20 11585773-6 2001 Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1 protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase activity. Tyrosine 21-29 cyclin dependent kinase 2 Homo sapiens 131-135 11485828-3 2001 A block in the G1/S cell cycle traverse associated with a decrease in CDK2 (cyclin dependent kinase) protein levels and retinoblastoma protein hypophosphorylation was also noted after PB and TB exposure. tributyrin 191-193 cyclin dependent kinase 2 Homo sapiens 70-74 11562278-13 2001 The antitumor sulfonamide E7070, causing a cellular accumulation in the G1 phase, has been shown to suppress the activation of CDK2 and cyclin E expression in HCT116 colorectal cancer cell line highly sensitive to the drug. Sulfonamides 14-25 cyclin dependent kinase 2 Homo sapiens 127-131 11562278-13 2001 The antitumor sulfonamide E7070, causing a cellular accumulation in the G1 phase, has been shown to suppress the activation of CDK2 and cyclin E expression in HCT116 colorectal cancer cell line highly sensitive to the drug. N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide 26-31 cyclin dependent kinase 2 Homo sapiens 127-131 11562278-4 2001 Flavopiridol is a potent inhibitor of cyclin-dependent kinases (CDKs). alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 64-68 11496322-7 2001 The tumor suppressor p53 and Cdk inhibitor p21, a known downstream effector of the p53, and association of p21 with Cdk2 were markedly induced in DHF-treated cells. dhf 146-149 cyclin dependent kinase 2 Homo sapiens 116-120 11593402-1 2001 Two specific inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor-derived MCF-7 cells. Roscovitine 61-72 cyclin dependent kinase 2 Homo sapiens 27-52 11593402-1 2001 Two specific inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor-derived MCF-7 cells. Roscovitine 61-72 cyclin dependent kinase 2 Homo sapiens 54-58 11593402-1 2001 Two specific inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor-derived MCF-7 cells. olomoucine 77-87 cyclin dependent kinase 2 Homo sapiens 27-52 11593402-1 2001 Two specific inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor-derived MCF-7 cells. olomoucine 77-87 cyclin dependent kinase 2 Homo sapiens 54-58 11532001-4 2001 We find that an ionic interaction participates in the recognition of the P + 3 position of the substrate and confirms an observation from structural studies indicating that a key element of this recognition is an interaction between the lysine at the P + 3 position and the Thr160 phosphate of Cdk2. Lysine 237-243 cyclin dependent kinase 2 Homo sapiens 294-298 11532001-4 2001 We find that an ionic interaction participates in the recognition of the P + 3 position of the substrate and confirms an observation from structural studies indicating that a key element of this recognition is an interaction between the lysine at the P + 3 position and the Thr160 phosphate of Cdk2. Phosphates 281-290 cyclin dependent kinase 2 Homo sapiens 294-298 11483735-6 2001 (iii) The processing of ICP0 forms E and F was blocked in HEL fibroblasts infected with R325 or with wild-type virus and treated with roscovitine, a specific inhibitor of cell cycle-dependent kinases cdc2, cdk2, and cdk5. Roscovitine 134-145 cyclin dependent kinase 2 Homo sapiens 206-210 11483735-14 2001 In contrast, the activity of cdk2 exhibited by immunoprecipitated protein was reduced and resistant to roscovitine and may represent a contaminating kinase activity. Roscovitine 103-114 cyclin dependent kinase 2 Homo sapiens 29-33 11418614-4 2001 Conversely, mutation of the lysine 1136 inhibited the ability of the cells to increase cyclin E and cdk2 expression, to maintain long term phosphorylation of the ERK MAPK, and to enter S-phase but had no effect on the ability of the cells to phosphorylate the p38 MAPK or to migrate on type I collagen in response to EGF. Lysine 28-34 cyclin dependent kinase 2 Homo sapiens 100-104 11521189-1 2001 Histone deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A arrest human papillomavirus (HPV)-positive carcinoma cells in G1 to S transition of the cell cycle, which is paralleled by an up-regulation of the cyclin-dependent kinase inhibitors (CKIs) p21CIP1 and p27KIP1 as well as the complete loss of cdk2 activity. Butyric Acid 38-53 cyclin dependent kinase 2 Homo sapiens 314-318 11507069-0 2001 A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. SU 9516 34-40 cyclin dependent kinase 2 Homo sapiens 8-12 11507069-2 2001 We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), a novel 3-substituted indolinone compound, binds to and selectively inhibits the activity of cdk2. SU 9516 18-93 cyclin dependent kinase 2 Homo sapiens 197-201 11507069-2 2001 We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), a novel 3-substituted indolinone compound, binds to and selectively inhibits the activity of cdk2. SU 9516 95-101 cyclin dependent kinase 2 Homo sapiens 197-201 11507069-5 2001 These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents. SU 9516 32-38 cyclin dependent kinase 2 Homo sapiens 54-58 11507069-5 2001 These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents. SU 9516 32-38 cyclin dependent kinase 2 Homo sapiens 120-124 11468187-6 2001 The levels of cdk2 also decreased after incubation with DFO, and especially 311, which may be important for explaining the decrease in hyperphosphorylated pRb. Deferoxamine 56-59 cyclin dependent kinase 2 Homo sapiens 14-18 11470744-8 2001 Taken together, these observations indicate transforming levels of okadaic acid elicit a G(1)-trapping effect by facilitating cell cycle progression to the G(1)/S checkpoint, where cells are trapped by mechanisms that include p21 (cip-1)-mediated inhibition of cdk2. Okadaic Acid 67-79 cyclin dependent kinase 2 Homo sapiens 261-265 11444827-4 2001 We showed that forskolin + IBMX inhibited serum-induced ERK activities, Rb hyperphosphorylation, Cdk2 activity, and p27(Kip1) downregulation and caused G1 arrest in MIA PaCa-2 cells. Colforsin 15-24 cyclin dependent kinase 2 Homo sapiens 97-101 11438644-1 2001 Inhibitors, activators, and substrates of cyclin-dependent kinases (cdks) utilize a cyclin-binding sequence, known as a Cy or RXL motif, to bind directly to the cyclin subunit. Cysteine 120-122 cyclin dependent kinase 2 Homo sapiens 68-72 11438644-2 2001 Alanine scanning mutagenesis of the Cy motif of the cdk inhibitor p21 revealed that the conserved arginine or leucine (constituting the conserved RXL sequence) was important for p21"s ability to inhibit cyclin E-cdk2 activity. Alanine 0-7 cyclin dependent kinase 2 Homo sapiens 212-216 11438644-2 2001 Alanine scanning mutagenesis of the Cy motif of the cdk inhibitor p21 revealed that the conserved arginine or leucine (constituting the conserved RXL sequence) was important for p21"s ability to inhibit cyclin E-cdk2 activity. Cysteine 36-38 cyclin dependent kinase 2 Homo sapiens 212-216 11438644-2 2001 Alanine scanning mutagenesis of the Cy motif of the cdk inhibitor p21 revealed that the conserved arginine or leucine (constituting the conserved RXL sequence) was important for p21"s ability to inhibit cyclin E-cdk2 activity. Arginine 98-106 cyclin dependent kinase 2 Homo sapiens 212-216 11438644-2 2001 Alanine scanning mutagenesis of the Cy motif of the cdk inhibitor p21 revealed that the conserved arginine or leucine (constituting the conserved RXL sequence) was important for p21"s ability to inhibit cyclin E-cdk2 activity. Leucine 110-117 cyclin dependent kinase 2 Homo sapiens 212-216 11438644-4 2001 Replacement of either of these two residues with small hydrophobic residues such as valine preserved p21"s inhibitory activity on cyclin E-cdk2, while mutations in either polar or charged residues dramatically impaired p21"s inhibitory activity. Valine 84-90 cyclin dependent kinase 2 Homo sapiens 139-143 11438644-7 2001 Finally, binding studies using p21 Cy mutants demonstrated that the Cy motif was essential for the association of p21 with cyclin E-cdk2 but not with cyclin A-cdk2. Cysteine 35-37 cyclin dependent kinase 2 Homo sapiens 132-136 11335721-6 2001 To overcome this problem, we synthesized a CDK4 mimic CDK2 protein in which the ATP binding pocket of CDK2 was replaced with that of CDK4. Adenosine Triphosphate 80-83 cyclin dependent kinase 2 Homo sapiens 54-58 11335721-6 2001 To overcome this problem, we synthesized a CDK4 mimic CDK2 protein in which the ATP binding pocket of CDK2 was replaced with that of CDK4. Adenosine Triphosphate 80-83 cyclin dependent kinase 2 Homo sapiens 102-106 11337496-5 2001 Treatment with estradiol alone resulted in a greater increase in cyclin D1 gene expression but markedly decreased p21 expression, with a concurrent increase in Cdk4 and Cdk2 activity and subsequent synchronous entry of cells into S phase. Estradiol 15-24 cyclin dependent kinase 2 Homo sapiens 169-173 11337496-9 2001 Thus the ability of estradiol to antagonize the insulin-induced increase in p21 gene expression, with consequent activation of cyclin E-Cdk2, is a central component of the synergistic stimulation of breast epithelial cell proliferation induced by simultaneous activation of the estrogen and insulin/IGF-I signaling pathways. Estradiol 20-29 cyclin dependent kinase 2 Homo sapiens 136-140 11479422-4 2001 As the pivotal residues around the most predominant R24C activating CDK4 mutation are invariant between CDK2 and CDK4, we speculated that the pivotal arginine (position 22 in CDK2), or a nearby residue, may be mutated in some melanomas, resulting in the diminution of its binding and inhibition by p27KIP1 or p21CIP1. Arginine 150-158 cyclin dependent kinase 2 Homo sapiens 104-108 11479422-4 2001 As the pivotal residues around the most predominant R24C activating CDK4 mutation are invariant between CDK2 and CDK4, we speculated that the pivotal arginine (position 22 in CDK2), or a nearby residue, may be mutated in some melanomas, resulting in the diminution of its binding and inhibition by p27KIP1 or p21CIP1. Arginine 150-158 cyclin dependent kinase 2 Homo sapiens 175-179 11463845-4 2001 In addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2 inhibitory activity of p21(Cip1). Threonine 45-48 cyclin dependent kinase 2 Homo sapiens 107-111 11463845-4 2001 In addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2 inhibitory activity of p21(Cip1). Threonine 45-48 cyclin dependent kinase 2 Homo sapiens 153-157 11444827-4 2001 We showed that forskolin + IBMX inhibited serum-induced ERK activities, Rb hyperphosphorylation, Cdk2 activity, and p27(Kip1) downregulation and caused G1 arrest in MIA PaCa-2 cells. 1-Methyl-3-isobutylxanthine 27-31 cyclin dependent kinase 2 Homo sapiens 97-101 11415463-5 2001 Further studies showed that PD098059 treatment significantly decreased Cdk2 kinase activity, most probably owing to an augmented level of p27/Kip1 associated with cyclin E-Cdk2 complexes. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 28-36 cyclin dependent kinase 2 Homo sapiens 71-75 11415463-5 2001 Further studies showed that PD098059 treatment significantly decreased Cdk2 kinase activity, most probably owing to an augmented level of p27/Kip1 associated with cyclin E-Cdk2 complexes. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 28-36 cyclin dependent kinase 2 Homo sapiens 172-176 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Phosphates 2-11 cyclin dependent kinase 2 Homo sapiens 149-153 11408350-5 2001 In addition, incubation with mevastatin arrested cells in the G1 phase of the cell cycle after 24 h with a switch to the G2/M phase after 72 h. This was accompanied by a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment. mevastatin 29-39 cyclin dependent kinase 2 Homo sapiens 215-218 11408350-5 2001 In addition, incubation with mevastatin arrested cells in the G1 phase of the cell cycle after 24 h with a switch to the G2/M phase after 72 h. This was accompanied by a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment. mevastatin 29-39 cyclin dependent kinase 2 Homo sapiens 260-265 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Arginine 24-27 cyclin dependent kinase 2 Homo sapiens 149-153 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Arginine 32-35 cyclin dependent kinase 2 Homo sapiens 149-153 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Lysine 44-47 cyclin dependent kinase 2 Homo sapiens 149-153 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Phosphates 86-95 cyclin dependent kinase 2 Homo sapiens 149-153 11427888-5 2001 A phosphate ion held by Arg 96, Arg 180 and Lys 205 occupies the same position as the phosphate group of the phosphothreonine in activated p38gamma, CDK2 or ERK2. Phosphothreonine 109-125 cyclin dependent kinase 2 Homo sapiens 149-153 11278991-0 2001 Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication. Threonine 45-48 cyclin dependent kinase 2 Homo sapiens 57-82 11278991-4 2001 Here, we identified that threonine 199 (Thr(199)) of NPM/B23 is the major phosphorylation target site of CDK2-cyclin E in vitro, and the same site is phosphorylated in vivo. Threonine 25-34 cyclin dependent kinase 2 Homo sapiens 105-109 11278991-4 2001 Here, we identified that threonine 199 (Thr(199)) of NPM/B23 is the major phosphorylation target site of CDK2-cyclin E in vitro, and the same site is phosphorylated in vivo. Threonine 40-43 cyclin dependent kinase 2 Homo sapiens 105-109 11278991-7 2001 These observations provide direct evidence that the CDK2-cyclin E-mediated phosphorylation on Thr(199) determines association and dissociation of NPM/B23 to the centrosomes, which is a critical control for the centrosome to initiate duplication. Threonine 94-97 cyclin dependent kinase 2 Homo sapiens 52-56 11322924-0 2001 Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Flavonoids 32-42 cyclin dependent kinase 2 Homo sapiens 133-137 11359910-7 2001 We also show that RB-mediated PCNA inhibition was dependent on downregulation of CDK2 activity, which was achieved through the downregulation of cyclin A. Rubidium 18-20 cyclin dependent kinase 2 Homo sapiens 81-85 11359910-8 2001 Importantly, restoration of cyclin-dependent kinase 2 (CDK2)-cyclin A and thus PCNA activity partially restored S-phase progression in the presence of active RB. Rubidium 158-160 cyclin dependent kinase 2 Homo sapiens 28-53 11359910-8 2001 Importantly, restoration of cyclin-dependent kinase 2 (CDK2)-cyclin A and thus PCNA activity partially restored S-phase progression in the presence of active RB. Rubidium 158-160 cyclin dependent kinase 2 Homo sapiens 55-59 11423993-0 2001 Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes. Lycopene 0-8 cyclin dependent kinase 2 Homo sapiens 176-180 11423993-12 2001 These results suggest that lycopene inhibits cell cycle progression via reduction of the cyclin D level and retention of p27 in cyclin E--cdk2, thus leading to inhibition of G(1) CDK activities. Lycopene 27-35 cyclin dependent kinase 2 Homo sapiens 138-142 11322924-4 2001 We demonstrate that flavonoids, which induced a cell cycle block in G1, inhibited the activity of CDK2 by 40-60%. Flavonoids 20-30 cyclin dependent kinase 2 Homo sapiens 98-102 11377199-10 2001 CONCLUSIONS: The accuracy of monomeric CDK2 as an inhibitor design template is restricted to the adenine binding site. Adenine 97-104 cyclin dependent kinase 2 Homo sapiens 39-43 11377199-11 2001 The general flexibility observed for the glycine loop and subtle changes to the phosphate binding site suggest a need to study interactions between inhibitors and active CDK2 in structure-based drug design programs. Glycine 41-48 cyclin dependent kinase 2 Homo sapiens 170-174 11377199-0 2001 Inhibitor binding to active and inactive CDK2: the crystal structure of CDK2-cyclin A/indirubin-5-sulphonate. Indirubin-5-sulfonate 86-108 cyclin dependent kinase 2 Homo sapiens 41-45 11354366-1 2001 Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Quinazolines 0-12 cyclin dependent kinase 2 Homo sapiens 63-67 11354366-3 2001 An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined. Quinazolines 43-54 cyclin dependent kinase 2 Homo sapiens 67-71 11377199-11 2001 The general flexibility observed for the glycine loop and subtle changes to the phosphate binding site suggest a need to study interactions between inhibitors and active CDK2 in structure-based drug design programs. Phosphates 80-89 cyclin dependent kinase 2 Homo sapiens 170-174 11354366-3 2001 An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined. Adenosine Triphosphate 104-107 cyclin dependent kinase 2 Homo sapiens 67-71 11377199-0 2001 Inhibitor binding to active and inactive CDK2: the crystal structure of CDK2-cyclin A/indirubin-5-sulphonate. Indirubin-5-sulfonate 86-108 cyclin dependent kinase 2 Homo sapiens 72-76 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. Indirubin-5-sulfonate 158-180 cyclin dependent kinase 2 Homo sapiens 42-46 11295047-2 2001 A block of cell cycle checkpoint by dexamethasone and genistein correlates with a selective induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 in a tumor suppressor p53-independent manner and abolishment of Cdk2 phosphorylation. Dexamethasone 36-49 cyclin dependent kinase 2 Homo sapiens 222-226 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. Indirubin-5-sulfonate 158-180 cyclin dependent kinase 2 Homo sapiens 211-215 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. Indirubin-5-sulfonate 158-180 cyclin dependent kinase 2 Homo sapiens 211-215 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. E226 182-186 cyclin dependent kinase 2 Homo sapiens 42-46 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. E226 182-186 cyclin dependent kinase 2 Homo sapiens 211-215 11377199-4 2001 To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2. E226 182-186 cyclin dependent kinase 2 Homo sapiens 211-215 11377199-8 2001 Conformational changes also result in subtle differences in hydrogen bonding and electrostatic interactions between E226"s sulphonate and CDK2"s phosphate binding site. Hydrogen 60-68 cyclin dependent kinase 2 Homo sapiens 138-142 11377199-8 2001 Conformational changes also result in subtle differences in hydrogen bonding and electrostatic interactions between E226"s sulphonate and CDK2"s phosphate binding site. e226"s sulphonate 116-133 cyclin dependent kinase 2 Homo sapiens 138-142 11377199-8 2001 Conformational changes also result in subtle differences in hydrogen bonding and electrostatic interactions between E226"s sulphonate and CDK2"s phosphate binding site. Phosphates 145-154 cyclin dependent kinase 2 Homo sapiens 138-142 11295047-2 2001 A block of cell cycle checkpoint by dexamethasone and genistein correlates with a selective induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 in a tumor suppressor p53-independent manner and abolishment of Cdk2 phosphorylation. Genistein 54-63 cyclin dependent kinase 2 Homo sapiens 222-226 11350919-5 2001 The immunoblot analysis revealed that resveratrol treatment causes a dose- and time-dependent (a) induction of WAF1/p21; (b) decrease in the protein expressions of cyclin D1, cyclin D2, and cyclin E; and (c) decrease in the protein expressions of cdk2, cdk4, and cdk6. Resveratrol 38-49 cyclin dependent kinase 2 Homo sapiens 247-251 11350919-7 2001 Taken together, our study suggests that resveratrol treatment of the cells causes an induction of WAF1/p21 that inhibits cyclin D1/D2-cdk6, cyclin D1/D2-cdk4, and cyclin E-cdk2 complexes, thereby imposing an artificial checkpoint at the G(1)-->S transition of the cell cycle. Resveratrol 40-51 cyclin dependent kinase 2 Homo sapiens 172-176 11264176-0 2001 Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function. Serine 105-111 cyclin dependent kinase 2 Homo sapiens 54-58 11300786-7 2001 In particular, ESI-MS demonstrated that Ser(315) was entirely phosphorylated after okadaic acid treatment, as confirmed biochemically by CDK2 kinase assay and by isoelectric focusing. Serine 40-43 cyclin dependent kinase 2 Homo sapiens 137-141 11300786-7 2001 In particular, ESI-MS demonstrated that Ser(315) was entirely phosphorylated after okadaic acid treatment, as confirmed biochemically by CDK2 kinase assay and by isoelectric focusing. Okadaic Acid 83-95 cyclin dependent kinase 2 Homo sapiens 137-141 11264176-0 2001 Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function. Threonine 116-125 cyclin dependent kinase 2 Homo sapiens 54-58 11264176-9 2001 Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. Threonine 141-150 cyclin dependent kinase 2 Homo sapiens 55-59 11264176-9 2001 Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. Serine 173-179 cyclin dependent kinase 2 Homo sapiens 55-59 11295463-4 2001 In this investigation, we compared the effect of Fas crosslinking by CH11, an anti-Fas mAb, with two cyclin-dependent kinase (CDK) inhibitors, a peptide that specifically inhibits CDK2 (cdk2 inh) and roscovitine, which inhibits CDK2, CDC2, and CDK5. Roscovitine 200-211 cyclin dependent kinase 2 Homo sapiens 186-190 11295463-7 2001 Both cdk2 inh and roscovitine induced cleavage of poly (ADP-ribose) polymerase (PARP) within 2 h. Roscovitine, however, led to the degradation of Rb, whereas cdk2 inh did not. Roscovitine 18-29 cyclin dependent kinase 2 Homo sapiens 158-162 11295463-7 2001 Both cdk2 inh and roscovitine induced cleavage of poly (ADP-ribose) polymerase (PARP) within 2 h. Roscovitine, however, led to the degradation of Rb, whereas cdk2 inh did not. Roscovitine 98-109 cyclin dependent kinase 2 Homo sapiens 5-9 11114297-4 2001 One site displays homology to a preferential D-type cyclin-dependent kinase site (serine 780) on the retinoblastoma susceptibility gene product (pRB) and, consistent with this homology, is more efficiently phosphorylated by cyclin D1-CDK4 than by the other cyclin-dependent kinases (CDK) that were tested. Serine 82-88 cyclin dependent kinase 2 Homo sapiens 234-237 11368357-5 2001 We also assessed the expressions of pRb, cyclin E, p21 and p27 and the activity of cdk2, the major regulator of S-phase entry, after exposure to cytosine-arabinoside (AraC) and daunorubicin (DNR), and found these proteins could characterize time- and dose-dependent cellular response to each drug. Cytarabine 167-171 cyclin dependent kinase 2 Homo sapiens 83-87 11368357-6 2001 We observed hyperphosphorylated pRb, increased levels of cyclin E and a high cdk2 activity, but no p21 induction, in AML cells exposed to 10(-6) M AraC. Cytarabine 147-151 cyclin dependent kinase 2 Homo sapiens 77-81 11368357-7 2001 After exposure to 10(-5) M AraC, corresponding to the serum concentration reached in high-dose AraC regimens (HDAraC), a strong p21 induction was observed, associated with similarly overexpressed cyclin E and even higher cdk2 activity than after 10(-6) M AraC, while apoptosis was significantly increased. Cytarabine 27-31 cyclin dependent kinase 2 Homo sapiens 221-225 11368357-7 2001 After exposure to 10(-5) M AraC, corresponding to the serum concentration reached in high-dose AraC regimens (HDAraC), a strong p21 induction was observed, associated with similarly overexpressed cyclin E and even higher cdk2 activity than after 10(-6) M AraC, while apoptosis was significantly increased. Cytarabine 95-99 cyclin dependent kinase 2 Homo sapiens 221-225 11562960-0 2001 The design and synthesis of purine inhibitors of CDK2. purine 28-34 cyclin dependent kinase 2 Homo sapiens 49-53 11562960-3 2001 Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects. purine 6-12 cyclin dependent kinase 2 Homo sapiens 84-89 11562960-3 2001 Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects. piperidine 145-155 cyclin dependent kinase 2 Homo sapiens 84-89 11562960-3 2001 Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects. purine 168-174 cyclin dependent kinase 2 Homo sapiens 84-89 11110801-9 2001 In vitro phosphorylation of PR with Cdk2 has revealed five additional in vitro Cdk2 phosphorylation sites: Ser(25), Ser(213), Thr(430), Ser(554), and Ser(676). Serine 107-110 cyclin dependent kinase 2 Homo sapiens 79-83 11110801-9 2001 In vitro phosphorylation of PR with Cdk2 has revealed five additional in vitro Cdk2 phosphorylation sites: Ser(25), Ser(213), Thr(430), Ser(554), and Ser(676). Serine 116-119 cyclin dependent kinase 2 Homo sapiens 79-83 11110801-9 2001 In vitro phosphorylation of PR with Cdk2 has revealed five additional in vitro Cdk2 phosphorylation sites: Ser(25), Ser(213), Thr(430), Ser(554), and Ser(676). Serine 116-119 cyclin dependent kinase 2 Homo sapiens 79-83 11110801-9 2001 In vitro phosphorylation of PR with Cdk2 has revealed five additional in vitro Cdk2 phosphorylation sites: Ser(25), Ser(213), Thr(430), Ser(554), and Ser(676). Serine 116-119 cyclin dependent kinase 2 Homo sapiens 79-83 11110801-11 2001 We confirmed the presence of the Cdk2-phosphorylated peptide containing Ser(213) in PR from in vivo labeled T47D cells, indicating that this is an in vivo site. Peptides 53-60 cyclin dependent kinase 2 Homo sapiens 33-37 11110801-11 2001 We confirmed the presence of the Cdk2-phosphorylated peptide containing Ser(213) in PR from in vivo labeled T47D cells, indicating that this is an in vivo site. Serine 72-75 cyclin dependent kinase 2 Homo sapiens 33-37 11237594-7 2001 Addition of olomoucine, a specific inhibitor of CDK2 and CDC2 activity on the other hand reduces the expression of the reporter. olomoucine 12-22 cyclin dependent kinase 2 Homo sapiens 48-52 11396178-4 2001 Investigation of cyclin-dependent kinases, Cdk2 and Cdc2, showed activity of Cdc2, but not Cdk2, increased markedly in response to curcumin. Curcumin 131-139 cyclin dependent kinase 2 Homo sapiens 43-47 11396181-0 2001 Complex regulation of CDK2 and G1 arrest during neuronal differentiation of human prostatic cancer TSU-Prl cells by staurosporine. Staurosporine 116-129 cyclin dependent kinase 2 Homo sapiens 22-26 11396181-4 2001 Treatment of TSU-Pr1 cells with staurosporine resulted in G1 arrest and suppression of CDK2 activity. Staurosporine 32-45 cyclin dependent kinase 2 Homo sapiens 87-91 11396181-10 2001 We propose that the complex regulation of CDK2 plays a key role in G1 arrest of TSU-Pr1 cells after treatment with staurosporine. Staurosporine 115-128 cyclin dependent kinase 2 Homo sapiens 42-46 11287748-4 2001 On the other hand, treatment of young HDFs during the late G1 transition with a specific inhibitor of CDK2, roscovitine, blocked the induction of TK RNA expression. Roscovitine 108-119 cyclin dependent kinase 2 Homo sapiens 102-106 11238922-6 2001 Second, HIRA was phosphorylated in vivo on two consensus cyclin-cdk2 phosphoacceptor sites and at least one of these, threonine 555, was phosphorylated by cyclin A-cdk2 in vitro. Threonine 118-127 cyclin dependent kinase 2 Homo sapiens 164-168 11238922-8 2001 Fourth, HIRA became phosphorylated on threonine 555 in S phase when cyclin-cdk2 kinases are active. Threonine 38-47 cyclin dependent kinase 2 Homo sapiens 75-79 11161293-6 2001 In the context of the Cdk2-pTpY/CycA complex, phospho-threonine is preferred over phospho-tyrosine by more than 10-fold. Phosphothreonine 46-63 cyclin dependent kinase 2 Homo sapiens 22-26 11170642-0 2001 Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717. Adenine 73-80 cyclin dependent kinase 2 Homo sapiens 27-52 11170642-0 2001 Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717. h717 99-103 cyclin dependent kinase 2 Homo sapiens 27-52 11170642-4 2001 We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. 2,6,9-trisubstituted purine 34-61 cyclin dependent kinase 2 Homo sapiens 162-166 11161293-6 2001 In the context of the Cdk2-pTpY/CycA complex, phospho-threonine is preferred over phospho-tyrosine by more than 10-fold. Phosphotyrosine 82-98 cyclin dependent kinase 2 Homo sapiens 22-26 11160853-7 2001 At 300 microM, N-BPs reduced expression of cyclin-dependent kinase (cdk) 2 and cdk4 and enhanced expression of p21(waf1) and p27(kip1) and their binding to cdks with corollary hypophosphorylation of retinoblastoma. n-bps 15-20 cyclin dependent kinase 2 Homo sapiens 43-74 11154267-8 2001 Transfection of MCF-7 cells with a dominant-negative Cdk2 construct inhibited the E(2)-dependent activation of ectopic Cdc25A. Estradiol 82-86 cyclin dependent kinase 2 Homo sapiens 53-57 11154267-9 2001 Supporting a role for Cdc25A in estrogen action, antisense CDC25A oligonucleotides inhibited estrogen-induced Cdk2 activation and DNA synthesis. Oligonucleotides 66-82 cyclin dependent kinase 2 Homo sapiens 110-114 11120603-8 2001 Furthermore, cycloheximide inhibited activation of CDK2:cyclin A, which normally precedes CDC2 kinase activation in caffeine-treated cells. Cycloheximide 13-26 cyclin dependent kinase 2 Homo sapiens 51-55 11067844-7 2001 These results provide kinetic proof that a Cy motif located a minimal distance from the SPXK is essential for optimal phosphorylation by Cdks and suggest that small chemicals that mimic the Cy motif would be specific inhibitors of substrate recognition by cyclin-dependent kinases. Cysteine 43-45 cyclin dependent kinase 2 Homo sapiens 137-141 11067844-7 2001 These results provide kinetic proof that a Cy motif located a minimal distance from the SPXK is essential for optimal phosphorylation by Cdks and suggest that small chemicals that mimic the Cy motif would be specific inhibitors of substrate recognition by cyclin-dependent kinases. Cysteine 190-192 cyclin dependent kinase 2 Homo sapiens 137-141 11029468-2 2001 A classic example is the regulation of the cell cycle control enzyme, CDK2/cyclin A, in which catalytic activation depends on phosphorylation at Thr(160) in CDK2. Threonine 145-148 cyclin dependent kinase 2 Homo sapiens 70-74 11029468-2 2001 A classic example is the regulation of the cell cycle control enzyme, CDK2/cyclin A, in which catalytic activation depends on phosphorylation at Thr(160) in CDK2. Threonine 145-148 cyclin dependent kinase 2 Homo sapiens 157-161 11716299-3 2001 These Cdk2 complexes integrate tyrosine phosphorylation and dephosphorylation inputs, resulting in the control of the number of rounds of fusion at discrete domains. Tyrosine 31-39 cyclin dependent kinase 2 Homo sapiens 6-10 11170137-8 2001 In other studies, silymarin, genistein or EGCG caused a strong induction of Cip1/p21 (up to 2.4-fold) and Kip1/p27 (up to 150-fold), and a strong decrease in CDK4 (40-90%) but had moderate effect on CDK2, and cyclins D1 and E. Silymarin 18-27 cyclin dependent kinase 2 Homo sapiens 199-203 11170137-8 2001 In other studies, silymarin, genistein or EGCG caused a strong induction of Cip1/p21 (up to 2.4-fold) and Kip1/p27 (up to 150-fold), and a strong decrease in CDK4 (40-90%) but had moderate effect on CDK2, and cyclins D1 and E. Genistein 29-38 cyclin dependent kinase 2 Homo sapiens 199-203 11170137-8 2001 In other studies, silymarin, genistein or EGCG caused a strong induction of Cip1/p21 (up to 2.4-fold) and Kip1/p27 (up to 150-fold), and a strong decrease in CDK4 (40-90%) but had moderate effect on CDK2, and cyclins D1 and E. epigallocatechin gallate 42-46 cyclin dependent kinase 2 Homo sapiens 199-203 11067844-3 2001 For both cyclin A-Cdk2 and cyclin E-Cdk2 enzymes, the presence of a Cy motif decreased the K(m(peptide)) 75-120-fold while the k(cat) remained unchanged. Cysteine 68-70 cyclin dependent kinase 2 Homo sapiens 18-22 11067844-3 2001 For both cyclin A-Cdk2 and cyclin E-Cdk2 enzymes, the presence of a Cy motif decreased the K(m(peptide)) 75-120-fold while the k(cat) remained unchanged. Cysteine 68-70 cyclin dependent kinase 2 Homo sapiens 36-40 11067844-3 2001 For both cyclin A-Cdk2 and cyclin E-Cdk2 enzymes, the presence of a Cy motif decreased the K(m(peptide)) 75-120-fold while the k(cat) remained unchanged. Peptides 95-102 cyclin dependent kinase 2 Homo sapiens 18-22 11067844-3 2001 For both cyclin A-Cdk2 and cyclin E-Cdk2 enzymes, the presence of a Cy motif decreased the K(m(peptide)) 75-120-fold while the k(cat) remained unchanged. Peptides 95-102 cyclin dependent kinase 2 Homo sapiens 36-40 11120603-8 2001 Furthermore, cycloheximide inhibited activation of CDK2:cyclin A, which normally precedes CDC2 kinase activation in caffeine-treated cells. Caffeine 116-124 cyclin dependent kinase 2 Homo sapiens 51-55 11113184-1 2001 Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the metazoan CDK-activating kinase (CAK), which activates CDKs, such as CDC2 and CDK2, through phosphorylation of a conserved threonine residue in the T loop. Threonine 187-196 cyclin dependent kinase 2 Homo sapiens 142-146 11113184-3 2001 We show that threonine-170 of CDK7 is phosphorylated in vitro by its targets, CDC2 and CDK2, which also phosphorylate serine-164 in the CDK7 T loop, a site that perfectly matches their consensus phosphorylation site. Threonine 13-22 cyclin dependent kinase 2 Homo sapiens 87-91 11113184-3 2001 We show that threonine-170 of CDK7 is phosphorylated in vitro by its targets, CDC2 and CDK2, which also phosphorylate serine-164 in the CDK7 T loop, a site that perfectly matches their consensus phosphorylation site. Serine 118-124 cyclin dependent kinase 2 Homo sapiens 87-91 11101352-1 2000 The identification of 8-ethyl-2-phenylamino-8H-pyrido[2, 3-d]pyrimidin-7-one (1) as an inhibitor of Cdk4 led to the initiation of a program to evaluate related pyrido[2, 3-d]pyrimidin-7-ones for inhibition of cyclin-dependent kinases (Cdks). 8-ethyl-2-phenylamino-8h-pyrido[2, 3-d]pyrimidin-7-one 22-76 cyclin dependent kinase 2 Homo sapiens 235-239 11759294-4 2001 In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Silybin 35-44 cyclin dependent kinase 2 Homo sapiens 173-177 11112337-0 2000 Regulation of cyclin-dependent kinase 2 activity by ceramide. Ceramides 52-60 cyclin dependent kinase 2 Homo sapiens 14-39 11112337-5 2000 Employing immunoprecipitation kinase assays, we found that ceramide specifically inhibited cyclin-dependent kinase CDK2, with a mild effect on CDC2 and significantly less effect on CDK4. Ceramides 59-67 cyclin dependent kinase 2 Homo sapiens 115-119 11112337-7 2000 Ceramide did not directly inhibit CDK2 in vitro but caused activation of p21, a major class of CDK-inhibitory proteins, and led to a greater association of p21 to CDK2. Ceramides 0-8 cyclin dependent kinase 2 Homo sapiens 163-167 11112337-8 2000 Using purified protein phosphatases, we showed that ceramide activated both protein phosphatase 1 and protein phosphatase 2A activities specific for CDK2 in vitro. Ceramides 52-60 cyclin dependent kinase 2 Homo sapiens 149-153 11112337-9 2000 Further, calyculin A and okadaic acid, both potent protein phosphatase inhibitors, together almost completely reversed the effects of ceramide on CDK2 inhibition. calyculin A 9-20 cyclin dependent kinase 2 Homo sapiens 146-150 11112337-9 2000 Further, calyculin A and okadaic acid, both potent protein phosphatase inhibitors, together almost completely reversed the effects of ceramide on CDK2 inhibition. Okadaic Acid 25-37 cyclin dependent kinase 2 Homo sapiens 146-150 11112337-9 2000 Further, calyculin A and okadaic acid, both potent protein phosphatase inhibitors, together almost completely reversed the effects of ceramide on CDK2 inhibition. Ceramides 134-142 cyclin dependent kinase 2 Homo sapiens 146-150 11112337-11 2000 Ceramide causes an increase in p21 association with CDK2 and through activation of protein phosphatases selectively regulates CDK2. Ceramides 0-8 cyclin dependent kinase 2 Homo sapiens 52-56 11112337-11 2000 Ceramide causes an increase in p21 association with CDK2 and through activation of protein phosphatases selectively regulates CDK2. Ceramides 0-8 cyclin dependent kinase 2 Homo sapiens 126-130 11032968-4 2000 Numerous active-site inhibitors of CDKs have been studied; the main limitation with these ATP antagonists is kinase specificity for CDKs. Adenosine Triphosphate 90-93 cyclin dependent kinase 2 Homo sapiens 35-39 11032968-4 2000 Numerous active-site inhibitors of CDKs have been studied; the main limitation with these ATP antagonists is kinase specificity for CDKs. Adenosine Triphosphate 90-93 cyclin dependent kinase 2 Homo sapiens 132-136 11329882-4 2000 We also found that butyrolactone I inhibits the CDK2 activity and enhances cell survival after an X-ray irradiation or doxorubicin treatment in both DLD1 (p21-/-) and DLD1 (p21+/+) cells. 4-Butyrolactone 19-32 cyclin dependent kinase 2 Homo sapiens 48-52 11101352-4 2000 X-ray crystallographic analysis of representative compounds bound to the related kinase, Cdk2, reveals that they occupy the ATP binding site. Adenosine Triphosphate 124-127 cyclin dependent kinase 2 Homo sapiens 89-93 11272092-7 2001 Exposure to butyrate increases the expression of the cyclin-dependent kinase inhibitors, p21/Cip1 and p27/Kip1, decreases the expression of cyclin A and cyclin B, inhibits the phosphorylation of the retinoblastoma protein (pRb), and decreases the activity of cdk1 and cdk2-associated kinases. Butyrates 12-20 cyclin dependent kinase 2 Homo sapiens 268-272 11121462-9 2000 Staurosporine-mediated G(0)/G(1) arrest targets the retinoblastoma protein (pRb) pathway and was accompanied by a rapid decrease in cyclin-dependent kinase (CDK) 4 protein levels, increased binding of CDK inhibitors p21 and p27 to CDK2, and inhibition of CDK2 activity in normal cells. Staurosporine 0-13 cyclin dependent kinase 2 Homo sapiens 157-160 11121462-9 2000 Staurosporine-mediated G(0)/G(1) arrest targets the retinoblastoma protein (pRb) pathway and was accompanied by a rapid decrease in cyclin-dependent kinase (CDK) 4 protein levels, increased binding of CDK inhibitors p21 and p27 to CDK2, and inhibition of CDK2 activity in normal cells. Staurosporine 0-13 cyclin dependent kinase 2 Homo sapiens 231-235 11121462-9 2000 Staurosporine-mediated G(0)/G(1) arrest targets the retinoblastoma protein (pRb) pathway and was accompanied by a rapid decrease in cyclin-dependent kinase (CDK) 4 protein levels, increased binding of CDK inhibitors p21 and p27 to CDK2, and inhibition of CDK2 activity in normal cells. Staurosporine 0-13 cyclin dependent kinase 2 Homo sapiens 255-259 11175348-8 2000 Association of PKCeta with cdk2 resulted in marked inhibition of cdk2-kinase activity when measured by phosphorylation of Rb. Rubidium 122-124 cyclin dependent kinase 2 Homo sapiens 27-31 11175348-8 2000 Association of PKCeta with cdk2 resulted in marked inhibition of cdk2-kinase activity when measured by phosphorylation of Rb. Rubidium 122-124 cyclin dependent kinase 2 Homo sapiens 65-69 11106396-6 2000 Aptamers fused to the catalytic domain of a ubiquitin ligase specifically decorated LexA-Cdk2 with ubiquitin moieties in vivo. lexa 84-88 cyclin dependent kinase 2 Homo sapiens 89-93 10934208-3 2000 PP2C alpha and PP2C beta 2 co-purified with Mg(2+)-dependent Cdk2/Cdk6 phosphatase activity in DEAE-Sepharose, Superdex-200, and Mono Q chromatographies. deae-sepharose 95-109 cyclin dependent kinase 2 Homo sapiens 61-65 10924512-10 2000 The mode of interactions of flavopiridol with GP is different from that of des-chloro-flavopiridol with CDK2, illustrating how different functional parts of the inhibitor can be used to provide specific and potent binding to two different enzymes. deschloroflavopiridol 75-98 cyclin dependent kinase 2 Homo sapiens 104-108 11089522-0 2000 A vitamin D3 analog induces a G1-phase arrest in CaCo-2 cells by inhibiting cdk2 and cdk6: roles of cyclin E, p21Waf1, and p27Kip1. Cholecalciferol 2-12 cyclin dependent kinase 2 Homo sapiens 76-80 11030153-7 2000 These results suggest that complex regulation of CDKs play a key role in G1 arrest of ML-1 after treatment with ATRA and GM-CSF. Tretinoin 112-116 cyclin dependent kinase 2 Homo sapiens 49-53 10931829-0 2000 The effects of changing the site of activating phosphorylation in CDK2 from threonine to serine. Threonine 76-85 cyclin dependent kinase 2 Homo sapiens 66-70 10931829-0 2000 The effects of changing the site of activating phosphorylation in CDK2 from threonine to serine. Serine 89-95 cyclin dependent kinase 2 Homo sapiens 66-70 10931829-1 2000 Cyclin-dependent kinases (CDKs) that control cell cycle progression are regulated in many ways, including activating phosphorylation of a conserved threonine residue. Threonine 148-157 cyclin dependent kinase 2 Homo sapiens 26-30 10931829-3 2000 Here we examine the effects of replacing this threonine residue in human CDK2 by serine. Threonine 46-55 cyclin dependent kinase 2 Homo sapiens 73-77 10931829-3 2000 Here we examine the effects of replacing this threonine residue in human CDK2 by serine. Serine 81-87 cyclin dependent kinase 2 Homo sapiens 73-77 10931829-12 2000 Combined with the more efficient phosphorylation of CDK2(Ser-160) by CAK, we suggest that one reason for the conservation of threonine as the site of activating phosphorylation may be to favor unphosphorylated CDKs following the degradation of cyclins. Threonine 125-134 cyclin dependent kinase 2 Homo sapiens 52-64 10931829-12 2000 Combined with the more efficient phosphorylation of CDK2(Ser-160) by CAK, we suggest that one reason for the conservation of threonine as the site of activating phosphorylation may be to favor unphosphorylated CDKs following the degradation of cyclins. Threonine 125-134 cyclin dependent kinase 2 Homo sapiens 210-214 11063125-3 2000 We report that RA enhances p27 expression, which results in increased association with cyclin E/cyclin-dependent kinase 2 complexes and suppression of their activity; however, antisense clones, which have greatly reduced RA-dependent p27 inducibility (NT2-p27AS), continue to synthesize DNA and are unable to differentiate properly in response to RA as determined by lack of neurite outgrowth and by the failure to modify surface antigens. Tretinoin 15-17 cyclin dependent kinase 2 Homo sapiens 96-121 10884382-8 2000 Furthermore, olomoucine, a specific inhibitor of Cdks, also blocked G-Rh2-induced apoptosis. olomoucine 13-23 cyclin dependent kinase 2 Homo sapiens 49-53 11079678-11 2000 Cerivastatin reduced the 3H-thymidine incorporation (164 +/- 11%, p < 0.01), inhibited Cdk2 activation and Rb phosphorylation, but did not prevent p27Kip1 down-regulation, nor p42mapk and p70S6K activation. cerivastatin 0-12 cyclin dependent kinase 2 Homo sapiens 90-94 11079678-12 2000 Mevalonate abrogated the effects of cerivastatin on Cdk2 and Rb but only partially rescued the 3H-thymidine incorporation (from 164 +/- 11% to 211 +/- 13%, n = 4, p < 0.01). Mevalonic Acid 0-10 cyclin dependent kinase 2 Homo sapiens 52-56 11079678-12 2000 Mevalonate abrogated the effects of cerivastatin on Cdk2 and Rb but only partially rescued the 3H-thymidine incorporation (from 164 +/- 11% to 211 +/- 13%, n = 4, p < 0.01). cerivastatin 36-48 cyclin dependent kinase 2 Homo sapiens 52-56 11007941-13 2000 Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. Silymarin 0-9 cyclin dependent kinase 2 Homo sapiens 177-181 11007941-13 2000 Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. Genistein 11-20 cyclin dependent kinase 2 Homo sapiens 177-181 11007941-13 2000 Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. epigallocatechin gallate 26-30 cyclin dependent kinase 2 Homo sapiens 177-181 11030153-8 2000 We also showed that an increase in CDK2-bound p27 and CDK4-bound p18 are caused by treatment with ATRA and a decrease in CDK6-bound cyclin D3 is induced synergistically by treatment with both reagents. Tretinoin 98-102 cyclin dependent kinase 2 Homo sapiens 35-39 10995387-12 2000 Importantly, mutation of Cdk2 phosphorylation sites to alanine abrogates the ability of p220 to activate the histone H2B promoter. Alanine 55-62 cyclin dependent kinase 2 Homo sapiens 25-29 10846177-16 2000 In vitro, Cdk2-Cyclin E, Cdk2-Cyclin A, and Cdc2-Cyclin B, but not Cdk4-Cyclin D1, phosphorylates the Thr-376 residue of huCdc7, suggesting possible regulation of huCdc7 by Cdks. Threonine 102-105 cyclin dependent kinase 2 Homo sapiens 10-14 10846177-16 2000 In vitro, Cdk2-Cyclin E, Cdk2-Cyclin A, and Cdc2-Cyclin B, but not Cdk4-Cyclin D1, phosphorylates the Thr-376 residue of huCdc7, suggesting possible regulation of huCdc7 by Cdks. Threonine 102-105 cyclin dependent kinase 2 Homo sapiens 25-29 10973815-4 2000 Molecular modelling based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. Adenosine Triphosphate 117-120 cyclin dependent kinase 2 Homo sapiens 54-58 11002421-6 2000 A loss of Cdc25A expression was associated with an increased inhibitory phosphotyrosine content of cyclin E- and cyclin A-associated cdk2 and may also contribute to G1 arrest following UVB irradiation. Phosphotyrosine 72-87 cyclin dependent kinase 2 Homo sapiens 133-137 11062725-4 2000 FACS analysis revealed that suppression of cell growth by PA was due to G1 arrest, with reduced phosphorylation of the retinoblastoma protein (pRb) and CDK2 activity. phenylacetic acid 58-60 cyclin dependent kinase 2 Homo sapiens 152-156 11062725-6 2000 Binding of p27Kip1 to CDK2 increased significantly following treatment with PA. phenylacetic acid 76-78 cyclin dependent kinase 2 Homo sapiens 22-26 11131647-7 2000 Only a weak relationship was found between the expression of cdk2 (P = 0.04) and PCNA (P = 0.05) and the doxorubicin response in vitro. Doxorubicin 105-116 cyclin dependent kinase 2 Homo sapiens 61-65 11062725-8 2000 Our results suggested that p27Kip1 might be a critical target in PA-mediated cell growth arrest in prostate cancer cells playing a key role in CDK2 inactivation followed by hypophosphorylation of pRB and subsequent G1 cell cycle arrest. phenylacetic acid 65-67 cyclin dependent kinase 2 Homo sapiens 143-147 10942587-15 2000 This protein binds the cyclin E/CDK2 complex that maintains Rb in a phosphorylated state. Rubidium 60-62 cyclin dependent kinase 2 Homo sapiens 32-36 10987270-1 2000 The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. Threonine 149-158 cyclin dependent kinase 2 Homo sapiens 141-145 10938106-6 2000 The p12(DOC-1)-mediated decrease of CDK2 was prevented if the p12(DOC-1) transfectants were grown in the presence of the proteosome inhibitor clasto-lactacystin beta-lactone, suggesting that p12(DOC-1) may target CDK2 for proteolysis. clasto-lactacystin beta-lactone 142-173 cyclin dependent kinase 2 Homo sapiens 36-40 10938106-6 2000 The p12(DOC-1)-mediated decrease of CDK2 was prevented if the p12(DOC-1) transfectants were grown in the presence of the proteosome inhibitor clasto-lactacystin beta-lactone, suggesting that p12(DOC-1) may target CDK2 for proteolysis. clasto-lactacystin beta-lactone 142-173 cyclin dependent kinase 2 Homo sapiens 213-217 10942602-4 2000 Roscovitine, a specific inhibitor of cyclin-Cdk2 complexes, prevents both phosphorylation and degradation of MyoD in G1. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 44-48 10962581-5 2000 Prevention of MAP Kinase activation by the MEK inhibitor PD98059 inhibits both activation and nuclear localization of cdk2 and S phase entry. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 57-64 cyclin dependent kinase 2 Homo sapiens 118-122 10896783-6 2000 Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Tretinoin 70-72 cyclin dependent kinase 2 Homo sapiens 155-159 10896783-6 2000 Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Tretinoin 70-72 cyclin dependent kinase 2 Homo sapiens 206-210 10903423-7 2000 Also estradiol-induced CDK2 activity was inhibited by BMP-2. Estradiol 5-14 cyclin dependent kinase 2 Homo sapiens 23-27 10956187-3 2000 The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine 69-122 cyclin dependent kinase 2 Homo sapiens 169-173 10956187-3 2000 The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine 124-130 cyclin dependent kinase 2 Homo sapiens 169-173 10956187-1 2000 Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. Guanine 12-20 cyclin dependent kinase 2 Homo sapiens 95-99 10956187-1 2000 Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. Guanine 12-20 cyclin dependent kinase 2 Homo sapiens 138-142 10956187-1 2000 Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. Pyrimidines 25-36 cyclin dependent kinase 2 Homo sapiens 138-142 10956187-2 2000 O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). NU2058 0-26 cyclin dependent kinase 2 Homo sapiens 76-80 10956187-2 2000 O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). NU2058 0-26 cyclin dependent kinase 2 Homo sapiens 135-139 10956187-2 2000 O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). NU2058 28-34 cyclin dependent kinase 2 Homo sapiens 76-80 10956187-2 2000 O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). NU2058 28-34 cyclin dependent kinase 2 Homo sapiens 135-139 10956187-2 2000 O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). Adenosine Triphosphate 97-100 cyclin dependent kinase 2 Homo sapiens 76-80 10956187-3 2000 The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Hydrogen 15-23 cyclin dependent kinase 2 Homo sapiens 169-173 10884347-5 2000 An alanine mutation at any one of four key positions abrogates the efficacy of a synthetic peptide containing this motif as an inhibitor of cyclin A-cdk2 phosphorylation of p53 protein. Alanine 3-10 cyclin dependent kinase 2 Homo sapiens 149-153 10884347-5 2000 An alanine mutation at any one of four key positions abrogates the efficacy of a synthetic peptide containing this motif as an inhibitor of cyclin A-cdk2 phosphorylation of p53 protein. Peptides 91-98 cyclin dependent kinase 2 Homo sapiens 149-153 10866826-1 2000 The cdk-activating kinase (CAK) activates cyclin-dependent kinases (cdks) that control cell-cycle progression by phosphorylating a threonine residue conserved in cdks. Threonine 131-140 cyclin dependent kinase 2 Homo sapiens 68-72 10914745-3 2000 The mechanism of this last effect is related to a PB-induced increase in p27Kip1, leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Phenylbutyrates 50-52 cyclin dependent kinase 2 Homo sapiens 123-148 10914745-3 2000 The mechanism of this last effect is related to a PB-induced increase in p27Kip1, leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Phenylbutyrates 50-52 cyclin dependent kinase 2 Homo sapiens 150-154 10866826-1 2000 The cdk-activating kinase (CAK) activates cyclin-dependent kinases (cdks) that control cell-cycle progression by phosphorylating a threonine residue conserved in cdks. Threonine 131-140 cyclin dependent kinase 2 Homo sapiens 162-166 10891109-0 2000 Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2. purine 29-35 cyclin dependent kinase 2 Homo sapiens 55-80 11256629-3 2000 By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Hydroxyurea 51-62 cyclin dependent kinase 2 Homo sapiens 147-151 11256629-3 2000 By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Hydroxyurea 51-62 cyclin dependent kinase 2 Homo sapiens 194-198 11256629-3 2000 By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Phosphotyrosine 152-167 cyclin dependent kinase 2 Homo sapiens 147-151 10867026-5 2000 Administration of dexamethasone at this, but not earlier stages, results in reduction of cyclin A and CDK2 levels with a parallel decrease in the associated kinase activity, dissociation of cyclin A-CDK2 from the E2F4-p130 complexes, and inhibition of G(1)/S transition. Dexamethasone 18-31 cyclin dependent kinase 2 Homo sapiens 102-106 10867026-5 2000 Administration of dexamethasone at this, but not earlier stages, results in reduction of cyclin A and CDK2 levels with a parallel decrease in the associated kinase activity, dissociation of cyclin A-CDK2 from the E2F4-p130 complexes, and inhibition of G(1)/S transition. Dexamethasone 18-31 cyclin dependent kinase 2 Homo sapiens 199-203 10891109-4 2000 X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. Adenosine Triphosphate 27-30 cyclin dependent kinase 2 Homo sapiens 57-61 10891109-4 2000 X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. olomoucine 32-42 cyclin dependent kinase 2 Homo sapiens 57-61 10891109-4 2000 X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. Roscovitine 44-55 cyclin dependent kinase 2 Homo sapiens 57-61 10844032-4 2000 Levels of CDK2 protein were elevated in proliferating Schwann cells cultured in serum and forskolin. Colforsin 90-99 cyclin dependent kinase 2 Homo sapiens 10-14 10827953-3 2000 This response involved activated Chk1 protein kinase but not the p53 pathway, and the persisting inhibitory tyrosine phosphorylation of Cdk2 blocked entry into S phase and DNA replication. Tyrosine 108-116 cyclin dependent kinase 2 Homo sapiens 136-140 10854062-7 2000 Thus, dephosphorylation of cdk2 as well as accumulation of cdk2 inhibitor is likely to contribute to the G1 phase arrest in phorbol ester-treated in U937 cells. Phorbol Esters 124-137 cyclin dependent kinase 2 Homo sapiens 27-31 10854062-7 2000 Thus, dephosphorylation of cdk2 as well as accumulation of cdk2 inhibitor is likely to contribute to the G1 phase arrest in phorbol ester-treated in U937 cells. Phorbol Esters 124-137 cyclin dependent kinase 2 Homo sapiens 59-63 10836716-9 2000 Nebivolol prevented Cdk2 activation without influencing p42mapk, S6K, pRB, and p27Kip1. Nebivolol 0-9 cyclin dependent kinase 2 Homo sapiens 20-24 10836716-10 2000 Thus, the new beta1-blocker nebivolol exhibits antiproliferative effect on human SMC through inactivation of Cdk2. Nebivolol 28-37 cyclin dependent kinase 2 Homo sapiens 109-113 10854062-0 2000 Cdk7- and Cdc25A-independent dephosphorylation of Cdk2 during phorbol ester-mediated cell cycle arrest in U937 cells. Phorbol Esters 62-75 cyclin dependent kinase 2 Homo sapiens 50-54 10854062-4 2000 Reduced activity of cdk2 correlated with cdk2 dephosphorylation and accumulation of cdk2 inhibitor p21Waf in phorbol ester-treated cells. Phorbol Esters 109-122 cyclin dependent kinase 2 Homo sapiens 20-24 10799321-5 2000 Taken together, these results show that anchoring of p27 or p21 KIPs to cyclin E via the N-terminal LFG-containing motif can block CAK access to its cdk2/cyclin E substrate. lfg 100-103 cyclin dependent kinase 2 Homo sapiens 149-153 10704940-7 2000 Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. panaxydol 98-107 cyclin dependent kinase 2 Homo sapiens 0-25 10788489-7 2000 Cell fractionation shows that cyclins A, E, and Cdk2 are bound to nuclei from mimosine-arrested cells. Mimosine 78-86 cyclin dependent kinase 2 Homo sapiens 48-52 10788489-8 2000 Exogenously added human cyclin A.Cdk2 and cyclin E.Cdk2 complexes, but not cyclin B1/Cdk1 or cyclin D2/Cdk6, can overcome inhibition of initiation by roscovitine in vitro. Roscovitine 150-161 cyclin dependent kinase 2 Homo sapiens 33-37 10788489-8 2000 Exogenously added human cyclin A.Cdk2 and cyclin E.Cdk2 complexes, but not cyclin B1/Cdk1 or cyclin D2/Cdk6, can overcome inhibition of initiation by roscovitine in vitro. Roscovitine 150-161 cyclin dependent kinase 2 Homo sapiens 51-55 10704940-7 2000 Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. panaxydol 98-107 cyclin dependent kinase 2 Homo sapiens 27-31 10704940-10 2000 These results indicate that panaxydol induces G(1) cell cycle arrest by decreasing Cdk2 activity and up-regulating p27(KIP1) protein expression. panaxydol 28-37 cyclin dependent kinase 2 Homo sapiens 83-87 10772807-3 2000 Hyperoxic exposure (95% O(2), 40-64 h) induced an S-phase arrest associated with acute inhibition of Cdk2 activity and DNA synthesis. o(2) 24-28 cyclin dependent kinase 2 Homo sapiens 101-105 10751146-4 2000 Treatment of cells with inhibitors of either CDKs (olomoucine, 200 microM) or RNA polymerase I (actinomycin D, 0.05 microgram/ml), results in a striking reorganization of CDK2 and p80 coilin to the nucleolar periphery. olomoucine 51-61 cyclin dependent kinase 2 Homo sapiens 45-49 10760826-8 2000 While the catalytic activity of all 3 G(1)-associated CDKs (CDK2, CDK4 and CDK6) was strongly inhibited in RA-treated LCLs, only CDK2-associated kinase activity was reduced in DG75 cells arrested in G(0)/G(1) by RA. Isotretinoin 107-109 cyclin dependent kinase 2 Homo sapiens 54-58 10760826-8 2000 While the catalytic activity of all 3 G(1)-associated CDKs (CDK2, CDK4 and CDK6) was strongly inhibited in RA-treated LCLs, only CDK2-associated kinase activity was reduced in DG75 cells arrested in G(0)/G(1) by RA. Isotretinoin 107-109 cyclin dependent kinase 2 Homo sapiens 60-64 10760826-8 2000 While the catalytic activity of all 3 G(1)-associated CDKs (CDK2, CDK4 and CDK6) was strongly inhibited in RA-treated LCLs, only CDK2-associated kinase activity was reduced in DG75 cells arrested in G(0)/G(1) by RA. Isotretinoin 212-214 cyclin dependent kinase 2 Homo sapiens 54-58 10751146-4 2000 Treatment of cells with inhibitors of either CDKs (olomoucine, 200 microM) or RNA polymerase I (actinomycin D, 0.05 microgram/ml), results in a striking reorganization of CDK2 and p80 coilin to the nucleolar periphery. olomoucine 51-61 cyclin dependent kinase 2 Homo sapiens 171-175 10751146-4 2000 Treatment of cells with inhibitors of either CDKs (olomoucine, 200 microM) or RNA polymerase I (actinomycin D, 0.05 microgram/ml), results in a striking reorganization of CDK2 and p80 coilin to the nucleolar periphery. Dactinomycin 96-109 cyclin dependent kinase 2 Homo sapiens 171-175 10841074-9 2000 The cooperative effect of ACV and IFN-gamma against the glioblastomas appears to be due to direct inhibition of DNA synthesis by ACV in the S phase of the cell cycle and induction by IFN-gamma of the tumor suppressor gene p21wAF1/CIP1, which in turn acts at the level of proliferating cell nuclear antigen (PCNA) and cyclin E/cyclin-dependent kinase 2 (Cdk2) binding and inhibition of function. Acyclovir 26-29 cyclin dependent kinase 2 Homo sapiens 353-357 10753466-4 2000 The structure of compound 4b (N-6-p-methoxybenzylamino derivative) in complex with human CDK2 was determined by X-ray crystallography, revealing the molecular basis of inhibition by this molecule. n-6-p-methoxybenzylamino 30-54 cyclin dependent kinase 2 Homo sapiens 89-93 10769144-9 2000 The p21WAF1/Cip1 protein levels were also increased in the CRE-decoy oligonucleotide treated cells accompanying a reduction in Cdk2- and cyclin E-dependent kinase activity and pRb phosphorylation. Oligonucleotides 69-84 cyclin dependent kinase 2 Homo sapiens 127-131 10741713-8 2000 In addition, we found down-regulation of cyclin B, cyclin E, and dephosphorylation of cdk2 in ciprofloxacin-treated bladder tumor cells. Ciprofloxacin 94-107 cyclin dependent kinase 2 Homo sapiens 86-90 11498372-3 2000 Co-crystallization with CDK2 shows that these flat heterocyclic hydrophobic compounds bind through two or three hydrogen bonds with the side chains of two amino acids located in the ATP-binding pocket of the kinase. Hydrogen 112-120 cyclin dependent kinase 2 Homo sapiens 24-28 11498372-3 2000 Co-crystallization with CDK2 shows that these flat heterocyclic hydrophobic compounds bind through two or three hydrogen bonds with the side chains of two amino acids located in the ATP-binding pocket of the kinase. Adenosine Triphosphate 182-185 cyclin dependent kinase 2 Homo sapiens 24-28 10766421-4 2000 Ceramide inhibited the kinase activities of cdk2 and cdk4 within 24 h of treatment. Ceramides 0-8 cyclin dependent kinase 2 Homo sapiens 44-48 10766421-5 2000 Ceramide-induced inhibition of cdk2 and cdk4 kinase activities was accompanied by increase of p27(kip1) in the cdks complexes. Ceramides 0-8 cyclin dependent kinase 2 Homo sapiens 31-35 10688905-1 2000 In this paper, we present evidence that activation of 5-hydroxytryptamine 2B (5-HT2B) receptors by serotonin (5-HT) leads to cell-cycle progression through retinoblastoma protein hyperphosphorylation and through activation of both cyclin D1/cdk4 and cyclin E/cdk2 kinases by a mechanism that depends on induction of cyclin D1 and cyclin E protein levels. Serotonin 99-108 cyclin dependent kinase 2 Homo sapiens 259-263 10741713-12 2000 Hence, the down-regulation of p21WAF1, together with the alterations in Bax and cdk2 as observed in our studies, may define a novel mechanism by which ciprofloxacin inhibits tumor cell growth and induces apoptotic cell death. Ciprofloxacin 151-164 cyclin dependent kinase 2 Homo sapiens 80-84 10741717-4 2000 In this study, we show that endoreduplication and polyploidation can be prevented by inhibiting the cyclin-dependent kinases (Cdks) by flavopiridol, a synthetic flavone presently undergoing phase II clinical trials. alvocidib 135-147 cyclin dependent kinase 2 Homo sapiens 126-130 10788588-6 2000 Potent specific inhibitors have been identified that bind to the ATP site of CDKs, mainly cyclin B-CDK1, cyclin A-CDK2, and cyclin D-CDK4 complexes, and inhibit kinase activity. Adenosine Triphosphate 65-68 cyclin dependent kinase 2 Homo sapiens 114-118 10741717-4 2000 In this study, we show that endoreduplication and polyploidation can be prevented by inhibiting the cyclin-dependent kinases (Cdks) by flavopiridol, a synthetic flavone presently undergoing phase II clinical trials. flavone 161-168 cyclin dependent kinase 2 Homo sapiens 126-130 10669749-7 2000 Blocking KAP expression by antisense KAP in a tetracycline-regulatable system results in a reduced population of S-phase cells and reduced Cdk2 kinase activity. Tetracycline 46-58 cyclin dependent kinase 2 Homo sapiens 139-143 10778740-8 2000 Although the functional C-terminal truncations disrupt the ATP-binding and active sites of Cdk2, reporter gene repression mediated by these truncated proteins is apparently due to phosphorylation of Pho4p, since a gene in which the essential lysine codon at position 33 was converted to an arginine codon does not complement the chromosomal gene disruption. Adenosine Triphosphate 59-62 cyclin dependent kinase 2 Homo sapiens 91-95 10761703-6 2000 Following genistein treatment of cells, an increased binding of p21 with Cdk2 and Cdc2 paralleled a significant decrease in Cdc2 and Cdk2 kinase activity with no change in Cdk2 and Cdc2 expression. Genistein 10-19 cyclin dependent kinase 2 Homo sapiens 133-137 10698512-9 2000 p27KiP1 immunodepletion experiments demonstrated that the DHT-mediated increase in p27Kip1 was sufficient to fully saturate and inhibit target cyclin E/ cdk2. Dihydrotestosterone 58-61 cyclin dependent kinase 2 Homo sapiens 153-157 10698512-10 2000 The inhibition of cyclin E/cdk2 by p27Kip1 contributes to G1 arrest of LNCaP following high dose DHT. Dihydrotestosterone 97-100 cyclin dependent kinase 2 Homo sapiens 27-31 10761703-6 2000 Following genistein treatment of cells, an increased binding of p21 with Cdk2 and Cdc2 paralleled a significant decrease in Cdc2 and Cdk2 kinase activity with no change in Cdk2 and Cdc2 expression. Genistein 10-19 cyclin dependent kinase 2 Homo sapiens 73-77 10652300-5 2000 Our data indicated that CDK2 can phosphorylate cyclin A on Ser-154. Serine 59-62 cyclin dependent kinase 2 Homo sapiens 24-28 10652300-6 2000 Site-directed mutagenesis of Ser-154 abolished the phosphorylation by recombinant CDK2 in vitro and the majority of cyclin A phosphorylation in the cell. Serine 29-32 cyclin dependent kinase 2 Homo sapiens 82-86 10652300-8 2000 Surprising, in marked contrast to cyclin E, where phosphorylation of Thr-380 by CDK2 is required for proteolysis, degradation of cyclin A was not affected by Ser-154 phosphorylation. Threonine 69-72 cyclin dependent kinase 2 Homo sapiens 80-84 10640426-10 2000 These results suggest that EB1089 can inhibit the proliferation of human myeloma cells, especially NCI-H929 cells, via a G(1) block in association with the induction of p27 and the reduction of CDK2 activity. seocalcitol 27-33 cyclin dependent kinase 2 Homo sapiens 194-198 10761703-6 2000 Following genistein treatment of cells, an increased binding of p21 with Cdk2 and Cdc2 paralleled a significant decrease in Cdc2 and Cdk2 kinase activity with no change in Cdk2 and Cdc2 expression. Genistein 10-19 cyclin dependent kinase 2 Homo sapiens 133-137 10633045-2 2000 Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. whi-p180 126-171 cyclin dependent kinase 2 Homo sapiens 216-220 10633045-2 2000 Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. 4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline 237-289 cyclin dependent kinase 2 Homo sapiens 189-214 10633045-0 2000 Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. anilinoquinazoline 20-40 cyclin dependent kinase 2 Homo sapiens 141-166 10633045-0 2000 Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. anilinoquinazoline 110-131 cyclin dependent kinase 2 Homo sapiens 141-166 10633045-4 2000 In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. Nitrogen 18-26 cyclin dependent kinase 2 Homo sapiens 105-109 10633045-2 2000 Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. whi-p180 126-171 cyclin dependent kinase 2 Homo sapiens 189-214 10633045-4 2000 In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. Quinazolines 48-59 cyclin dependent kinase 2 Homo sapiens 105-109 10633045-4 2000 In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. Hydrogen 71-79 cyclin dependent kinase 2 Homo sapiens 105-109 10633045-4 2000 In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. Oxygen 240-246 cyclin dependent kinase 2 Homo sapiens 105-109 10633045-4 2000 In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. Peptides 260-267 cyclin dependent kinase 2 Homo sapiens 105-109 10633045-5 2000 The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. Quinazolines 79-90 cyclin dependent kinase 2 Homo sapiens 25-29 10633045-5 2000 The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. Lysine 133-136 cyclin dependent kinase 2 Homo sapiens 25-29 10633045-5 2000 The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. Phenylalanine 144-147 cyclin dependent kinase 2 Homo sapiens 25-29 10644979-4 2000 Our findings demonstrate that the retinoic acid-dependent growth arrest of LAN-5 neuroblastoma cell line is associated to a very large accumulation (>tenfold) of p27Kip1 protein, a cyclin-dependent kinase inhibitor; the protein binds and inhibits cyclin-dependent kinase 2, 4 and 6 activities, thus hampering pRb and p107 phosphorylation. Tretinoin 34-47 cyclin dependent kinase 2 Homo sapiens 250-275 10623573-4 2000 We found that herbimycin A prevented serum-induced downregulation of the cyclin-dependent kinase inhibitor p27(Kip1), thereby leading to inactivation of the protein kinase activity of CDK2. herbimycin 14-26 cyclin dependent kinase 2 Homo sapiens 184-188 11341037-6 2000 Methionine restriction led to accumulation of the cyclin-dependent kinase inhibitors p21 and p27, as determined by Western blot analysis, and inhibited the enzymatic activities of the cyclin-dependent kinases CDK2 and cdc2, as determined by an in vitro kinase assay: However, methionine restriction had little or no effect on CDK2 or cdc2 protein levels. Methionine 0-10 cyclin dependent kinase 2 Homo sapiens 209-213 10874474-4 2000 The activity of cdk2 was inhibited in response to ceramide during this process. Ceramides 50-58 cyclin dependent kinase 2 Homo sapiens 16-20 10874474-10 2000 In pRb+/+ cells, ceramide-mediated G1 arrest was accompanied by the accumulation of hypophosphorylated pRb and p21 associated with cdk2. Ceramides 17-25 cyclin dependent kinase 2 Homo sapiens 131-135 10874474-11 2000 Together, these results suggest that p21, induced through p53-independent pathway, participates in the induction of pRb dephosphorylation by inhibiting cdk2 activity during ceramide-mediated G1 arrest in hepatocarcinoma cells. Ceramides 173-181 cyclin dependent kinase 2 Homo sapiens 152-156 11341037-6 2000 Methionine restriction led to accumulation of the cyclin-dependent kinase inhibitors p21 and p27, as determined by Western blot analysis, and inhibited the enzymatic activities of the cyclin-dependent kinases CDK2 and cdc2, as determined by an in vitro kinase assay: However, methionine restriction had little or no effect on CDK2 or cdc2 protein levels. Methionine 0-10 cyclin dependent kinase 2 Homo sapiens 326-330 11341037-6 2000 Methionine restriction led to accumulation of the cyclin-dependent kinase inhibitors p21 and p27, as determined by Western blot analysis, and inhibited the enzymatic activities of the cyclin-dependent kinases CDK2 and cdc2, as determined by an in vitro kinase assay: However, methionine restriction had little or no effect on CDK2 or cdc2 protein levels. Methionine 276-286 cyclin dependent kinase 2 Homo sapiens 209-213 10602500-2 1999 Novel potential functions of Cdk2 have been uncovered by using two potent and specific inhibitors of its kinase activity, roscovitine and olomoucine, on human wt p53-expresser untransformed and tumor-derived cells. Roscovitine 122-133 cyclin dependent kinase 2 Homo sapiens 29-33 10585280-0 1999 Activation of a cAMP pathway and induction of melanogenesis correlate with association of p16(INK4) and p27(KIP1) to CDKs, loss of E2F-binding activity, and premature senescence of human melanocytes. Cyclic AMP 16-20 cyclin dependent kinase 2 Homo sapiens 117-121 10611320-5 1999 Whole-cell lysates from TGF-beta-treated cells showed inhibition of Cdk2 Thr(160) Cdk activating kinase (CAK) activity; however, cyclin H:Cdk7 activity, a previously assumed mammalian CAK, was not altered. Threonine 73-76 cyclin dependent kinase 2 Homo sapiens 68-72 10602500-2 1999 Novel potential functions of Cdk2 have been uncovered by using two potent and specific inhibitors of its kinase activity, roscovitine and olomoucine, on human wt p53-expresser untransformed and tumor-derived cells. olomoucine 138-148 cyclin dependent kinase 2 Homo sapiens 29-33 10665655-0 1999 G1-checkpoint function including a cyclin-dependent kinase 2 regulatory pathway as potential determinant of 7-hydroxystaurosporine (UCN-01)-induced apoptosis and G1-phase accumulation. 7-hydroxystaurosporine 108-130 cyclin dependent kinase 2 Homo sapiens 35-60 10698260-0 1999 Both low and high concentrations of staurosporine induce G1 arrest through down-regulation of cyclin E and cdk2 expression. Staurosporine 36-49 cyclin dependent kinase 2 Homo sapiens 107-111 10698260-6 1999 Moreover, 200 nM staurosporine increased the expression of p53 and p21 proteins and inhibited the expression of cyclin E and cdk2 proteins, suggesting that the cells were arrested in the G1 phase of the next cycle. Staurosporine 17-30 cyclin dependent kinase 2 Homo sapiens 125-129 10757037-0 1999 Differential regulation of the major cyclin-dependent kinases, cdk2 and cdc2, during cell cycle progression in human lymphocytes exposed to heptachlor. Heptachlor 140-150 cyclin dependent kinase 2 Homo sapiens 63-67 10597298-5 1999 SC-alpha alpha delta 9 also enhanced tyrosine phosphorylation of both Cdk2 and Cdk4, and decreased Cdk4 kinase activity. Tyrosine 37-45 cyclin dependent kinase 2 Homo sapiens 70-74 10567774-2 1999 In this study we investigated the cellular effects of olomoucine in two human Burkitt"s lymphoma cell lines, WMN (containing wild-type p53) and CA46 (containing mutant p53), and found that in consistency with its ability to block the activity of cyclin E/Cdk2 and cyclin B1/Cdc2 kinases, olomoucine caused cell cycle arrest at both G1/S and G2/S boundaries. olomoucine 54-64 cyclin dependent kinase 2 Homo sapiens 255-259 10527623-8 1999 Olomoucine and roscovitine, the potent p34(cdc2) and CDK2 inhibitors, effectively blocked CD437-mediated cyclin A- and B-dependent kinase activation and prevented CD437-induced cell death. olomoucine 0-10 cyclin dependent kinase 2 Homo sapiens 53-57 10527623-8 1999 Olomoucine and roscovitine, the potent p34(cdc2) and CDK2 inhibitors, effectively blocked CD437-mediated cyclin A- and B-dependent kinase activation and prevented CD437-induced cell death. Roscovitine 15-26 cyclin dependent kinase 2 Homo sapiens 53-57 10571528-4 1999 In contrast, cGMP inhibits cyclin D1 expression, inhibits cdk4 activation, and delays platelet-derived growth factor-mediated cdk2 activation, resulting in a delay in G(1)/S transition. Cyclic GMP 13-17 cyclin dependent kinase 2 Homo sapiens 126-130 10571528-5 1999 A transient increase in p27(Kip1) in cdk2 immunoprecipitates, without changes in total cellular p27(Kip1) levels, correlates with the delay in cdk2 activation caused by cGMP. Cyclic GMP 169-173 cyclin dependent kinase 2 Homo sapiens 37-41 10571528-5 1999 A transient increase in p27(Kip1) in cdk2 immunoprecipitates, without changes in total cellular p27(Kip1) levels, correlates with the delay in cdk2 activation caused by cGMP. Cyclic GMP 169-173 cyclin dependent kinase 2 Homo sapiens 143-147 10597222-8 1999 Likewise, inhibition of CDK2 by transfection of a dominant negative CDK2 in NT2/D1 cells or treatment with the kinase inhibitor olomucine induced growth arrest but not differentiation. olomoucine 128-137 cyclin dependent kinase 2 Homo sapiens 24-28 10537037-5 1999 Cyclic AMP strongly inhibited cdk1 and cdk2 expression. Cyclic AMP 0-10 cyclin dependent kinase 2 Homo sapiens 39-43 10537037-13 1999 We conclude that cyclic AMP inhibits progression of the cell cycle in astrocytes at least by preventing the expression of the regulatory subunits, cyclins D1 and A, and catalytic subunits, cdk1 and cdk2, of cyclin-regulated protein kinases. Cyclic AMP 17-27 cyclin dependent kinase 2 Homo sapiens 198-202 10559988-2 1999 For activity, CDKs require association with a cyclin and phosphorylation by a separate protein kinase at a conserved threonine residue (T160 in CDK2). Threonine 117-126 cyclin dependent kinase 2 Homo sapiens 14-18 10551775-5 1999 Within 11 h of DEX treatment, this was accompanied by an accumulation of cells in the G1 phase of the cell cycle with a corresponding decreased proportion of cells in the S phase and decreased CDK2 activity. Dexamethasone 15-18 cyclin dependent kinase 2 Homo sapiens 193-197 10559988-2 1999 For activity, CDKs require association with a cyclin and phosphorylation by a separate protein kinase at a conserved threonine residue (T160 in CDK2). Threonine 117-126 cyclin dependent kinase 2 Homo sapiens 144-148 10559988-4 1999 This structure provides an explanation for the specificity of CDK2 towards the proline that follows the phosphorylatable serine of the substrate peptide, and the requirement for the basic residue in the P+3 position of the substrate. Proline 79-86 cyclin dependent kinase 2 Homo sapiens 62-66 10559988-4 1999 This structure provides an explanation for the specificity of CDK2 towards the proline that follows the phosphorylatable serine of the substrate peptide, and the requirement for the basic residue in the P+3 position of the substrate. Serine 121-127 cyclin dependent kinase 2 Homo sapiens 62-66 10559988-4 1999 This structure provides an explanation for the specificity of CDK2 towards the proline that follows the phosphorylatable serine of the substrate peptide, and the requirement for the basic residue in the P+3 position of the substrate. Peptides 145-152 cyclin dependent kinase 2 Homo sapiens 62-66 10575317-5 1999 In one tumor, DNA sequencing showed a GCG-ACG (alanine-threonine) substitution at codon 148, a polymorphism in exon 2 of CDKN2. alanine-threonine 47-64 cyclin dependent kinase 2 Homo sapiens 121-126 10502407-6 1999 We demonstrated that pRB phosphorylation, cdk2 activity needed for this phosphorylation, and the levels of cyclin A, D, and E were inhibited after 24 h of lovastatin treatment, while the levels of p27(Kip1) were elevated. Lovastatin 155-165 cyclin dependent kinase 2 Homo sapiens 42-46 10502413-4 1999 The induction of the CKIs by modulators of cAMP such as cholera toxin (CT) + 1-isobutyl-3-methylxanthine (IBMX) and lovastatin fluctuates with biphasic kinetics (although the kinetics of CKI induction with CT + IBMX treatment are different from that of lovastatin) and is depicted by the periodic accumulation of lower molecular weight forms of p21 and p27 which also correlate with fluctuations in CDK2 activity. Cyclic AMP 43-47 cyclin dependent kinase 2 Homo sapiens 399-403 10499802-6 1999 However, it is not until near the end of G1, when cyclin E is expressed and Cdk2 is activated, that Rb is prevented from binding and inactivating E2F. Rubidium 100-102 cyclin dependent kinase 2 Homo sapiens 76-80 10502413-4 1999 The induction of the CKIs by modulators of cAMP such as cholera toxin (CT) + 1-isobutyl-3-methylxanthine (IBMX) and lovastatin fluctuates with biphasic kinetics (although the kinetics of CKI induction with CT + IBMX treatment are different from that of lovastatin) and is depicted by the periodic accumulation of lower molecular weight forms of p21 and p27 which also correlate with fluctuations in CDK2 activity. 1-Methyl-3-isobutylxanthine 106-110 cyclin dependent kinase 2 Homo sapiens 399-403 10502413-4 1999 The induction of the CKIs by modulators of cAMP such as cholera toxin (CT) + 1-isobutyl-3-methylxanthine (IBMX) and lovastatin fluctuates with biphasic kinetics (although the kinetics of CKI induction with CT + IBMX treatment are different from that of lovastatin) and is depicted by the periodic accumulation of lower molecular weight forms of p21 and p27 which also correlate with fluctuations in CDK2 activity. Lovastatin 116-126 cyclin dependent kinase 2 Homo sapiens 399-403 10462699-7 1999 Immunocomplex kinase experiments showed that EGCG inhibited the activities of cyclin-dependent kinase 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. epigallocatechin gallate 45-49 cyclin dependent kinase 2 Homo sapiens 78-103 10462699-7 1999 Immunocomplex kinase experiments showed that EGCG inhibited the activities of cyclin-dependent kinase 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. epigallocatechin gallate 45-49 cyclin dependent kinase 2 Homo sapiens 105-109 10462699-8 1999 As the cells were exposed to EGCG (30 microM) over 24 h a gradual loss of both Cdk2 and Cdk4 kinase activities occurred. epigallocatechin gallate 29-33 cyclin dependent kinase 2 Homo sapiens 79-83 10462699-12 1999 These results suggest that EGCG either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins such as Cdk2 and Cdk4 or mediates the induction of Cdk inhibitor p21 and p27. epigallocatechin gallate 27-31 cyclin dependent kinase 2 Homo sapiens 159-163 10706449-8 1999 The levels of CDK2 activity were inhibited approximately 60% in ATRA-treated cells, suggesting that the increased p21 levels were sufficient to inhibit CDK activity and cause RB hypophosphorylation. Tretinoin 64-68 cyclin dependent kinase 2 Homo sapiens 14-17 10509743-9 1999 We have demonstrated that EGCG inhibits the activities of cyclin-dependent kinases 2 and 4; meanwhile, EGCG induces the expression of the Cdk inhibitors p21 and p27. epigallocatechin gallate 26-30 cyclin dependent kinase 2 Homo sapiens 58-90 10509743-9 1999 We have demonstrated that EGCG inhibits the activities of cyclin-dependent kinases 2 and 4; meanwhile, EGCG induces the expression of the Cdk inhibitors p21 and p27. epigallocatechin gallate 26-30 cyclin dependent kinase 2 Homo sapiens 138-141 10509743-9 1999 We have demonstrated that EGCG inhibits the activities of cyclin-dependent kinases 2 and 4; meanwhile, EGCG induces the expression of the Cdk inhibitors p21 and p27. epigallocatechin gallate 103-107 cyclin dependent kinase 2 Homo sapiens 138-141 10706449-6 1999 ATRA decreased the level of phosphorylation of the RB protein at doses > 5 x 10(-9) M and also induced a five fold increase in p21WAF1, while levels of p27KIP1 and CDK2 were unchanged. Tretinoin 0-4 cyclin dependent kinase 2 Homo sapiens 167-171 10706449-8 1999 The levels of CDK2 activity were inhibited approximately 60% in ATRA-treated cells, suggesting that the increased p21 levels were sufficient to inhibit CDK activity and cause RB hypophosphorylation. Tretinoin 64-68 cyclin dependent kinase 2 Homo sapiens 14-18 10493518-1 1999 Flavopiridol is a novel flavonoid that induces cell cycle arrest at different stages of the cell cycle because of the inhibition of cyclin-dependent kinases (cdks). alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 158-162 10493518-1 1999 Flavopiridol is a novel flavonoid that induces cell cycle arrest at different stages of the cell cycle because of the inhibition of cyclin-dependent kinases (cdks). Flavonoids 24-33 cyclin dependent kinase 2 Homo sapiens 158-162 10493518-3 1999 A. Carlson et al., Cancer Res., 56: 2973-2978, 1996), we observed that exposure of the MCF-7 breast carcinoma cell line to flavopiridol resulted in G1-S arrest, which was associated with the loss of cdk4 and cdk2 activity by 24 h of exposure. alvocidib 123-135 cyclin dependent kinase 2 Homo sapiens 208-212 10454524-9 1999 Previous and present results indicate that group 1 tyrphostins, which inhibit Cdk2 activation, and group 2 tyrphostins, represented by AG1478, a potent epidermal growth factor receptor kinase inhibitor, induce cell cycle arrest; and, in the case of HF-1 cells, apoptosis and differentiation. Tyrphostins 51-62 cyclin dependent kinase 2 Homo sapiens 78-82 10628338-3 1999 Lactacystin increased the cellular level of p53 and cdk2-associated p21WAF1/CIP1 leading to cdk2 inactivation. lactacystin 0-11 cyclin dependent kinase 2 Homo sapiens 52-56 10628338-3 1999 Lactacystin increased the cellular level of p53 and cdk2-associated p21WAF1/CIP1 leading to cdk2 inactivation. lactacystin 0-11 cyclin dependent kinase 2 Homo sapiens 92-96 10511310-4 1999 We show that the elevated cyclin A-Cdk2 activity is due to the combination of increased accumulation and stabilization of cyclin A bound to a faster-migrating species of Cdk2 believed to be the active threonine 160 phosphorylated form and a substantial reduction in complexed p27. Threonine 201-210 cyclin dependent kinase 2 Homo sapiens 35-39 10511310-4 1999 We show that the elevated cyclin A-Cdk2 activity is due to the combination of increased accumulation and stabilization of cyclin A bound to a faster-migrating species of Cdk2 believed to be the active threonine 160 phosphorylated form and a substantial reduction in complexed p27. Threonine 201-210 cyclin dependent kinase 2 Homo sapiens 170-174 10454565-12 1999 Furthermore, Cdc25A overexpression induces a tyrosine dephosphorylation of Cdk2. Tyrosine 45-53 cyclin dependent kinase 2 Homo sapiens 75-79 10438723-8 1999 Thus, retinoic acid induced a rapid, but transient increased binding of p21(Cip1) to CDK2. Tretinoin 6-19 cyclin dependent kinase 2 Homo sapiens 85-89 10432313-7 1999 Lyn was associated with Cdk2; Cdk2-associated Lyn was heavily phosphorylated on serine and threonine residues both in vitro and in situ during S-phase. Serine 80-86 cyclin dependent kinase 2 Homo sapiens 30-34 10432313-7 1999 Lyn was associated with Cdk2; Cdk2-associated Lyn was heavily phosphorylated on serine and threonine residues both in vitro and in situ during S-phase. Threonine 91-100 cyclin dependent kinase 2 Homo sapiens 30-34 10652602-5 1999 Analysis of G1 regulatory proteins demonstrated that the protein levels of cyclin-dependent kinase (CDK) 2, CDK4, CDK6 and cyclin E were decreased after treatment with lovastatin (10 microM) in a time-dependent manner, but not cyclin D1. Lovastatin 168-178 cyclin dependent kinase 2 Homo sapiens 100-106 10428798-8 1999 Finally, enhancement of ER transcriptional activation by cyclin A is evident in the absence and presence of estradiol, as well as in the presence of tamoxifen, suggesting that the effect of the cyclin A-CDK2 on ER transcriptional activation is AF-2-independent. Tamoxifen 149-158 cyclin dependent kinase 2 Homo sapiens 203-207 10428798-9 1999 These results indicate that the enhancement of ER transcriptional activation by the cyclin A-CDK2 complex is mediated via the AF-1 domain by phosphorylation of serines 104 and 106. Serine 160-167 cyclin dependent kinase 2 Homo sapiens 93-97 10473102-2 1999 In this study, we provide the first direct evidence showing that dihydrotestosterone (DHT), a major proliferation regulator of prostate cancer, can down-regulate p27Kip1 and stimulate cyclin-dependent kinase-2 (CDK2) activity in established prostate cancer cell lines. Dihydrotestosterone 65-84 cyclin dependent kinase 2 Homo sapiens 184-209 10473102-2 1999 In this study, we provide the first direct evidence showing that dihydrotestosterone (DHT), a major proliferation regulator of prostate cancer, can down-regulate p27Kip1 and stimulate cyclin-dependent kinase-2 (CDK2) activity in established prostate cancer cell lines. Dihydrotestosterone 65-84 cyclin dependent kinase 2 Homo sapiens 211-215 10473102-2 1999 In this study, we provide the first direct evidence showing that dihydrotestosterone (DHT), a major proliferation regulator of prostate cancer, can down-regulate p27Kip1 and stimulate cyclin-dependent kinase-2 (CDK2) activity in established prostate cancer cell lines. Dihydrotestosterone 86-89 cyclin dependent kinase 2 Homo sapiens 184-209 10473102-2 1999 In this study, we provide the first direct evidence showing that dihydrotestosterone (DHT), a major proliferation regulator of prostate cancer, can down-regulate p27Kip1 and stimulate cyclin-dependent kinase-2 (CDK2) activity in established prostate cancer cell lines. Dihydrotestosterone 86-89 cyclin dependent kinase 2 Homo sapiens 211-215 10473102-5 1999 Stimulation of cell proliferation by DHT and/or EGF was associated with increased CDK2 activity and a decreased level of p27Kip1. Dihydrotestosterone 37-40 cyclin dependent kinase 2 Homo sapiens 82-86 10393546-2 1999 The IC50 value of p27 increased with increasing Cdk2/Cyclin E concentrations while it remained constant at various ATP and histone H1 concentrations, suggesting that p27 acts as a tight binding inhibitor of Cdk2/Cyclin E. We also found that p27 could be phosphorylated by Cdk2/Cyclin E only at high enzyme concentrations, and that p27 forms a stable interaction with Cdk2/Cyclin E regardless of its phosphorylation state. Adenosine Triphosphate 115-118 cyclin dependent kinase 2 Homo sapiens 207-211 10393546-2 1999 The IC50 value of p27 increased with increasing Cdk2/Cyclin E concentrations while it remained constant at various ATP and histone H1 concentrations, suggesting that p27 acts as a tight binding inhibitor of Cdk2/Cyclin E. We also found that p27 could be phosphorylated by Cdk2/Cyclin E only at high enzyme concentrations, and that p27 forms a stable interaction with Cdk2/Cyclin E regardless of its phosphorylation state. Adenosine Triphosphate 115-118 cyclin dependent kinase 2 Homo sapiens 207-211 10428798-0 1999 Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. Serine 100-107 cyclin dependent kinase 2 Homo sapiens 136-140 10428798-3 1999 Within ER AF-1, serines 104, 106, and 118 represent potential CDK phosphorylation sites, and in this current study, we ascertain their importance in mediating cyclin A-CDK2-dependent enhancement of ER transcriptional activity. Serine 16-23 cyclin dependent kinase 2 Homo sapiens 168-172 10393546-2 1999 The IC50 value of p27 increased with increasing Cdk2/Cyclin E concentrations while it remained constant at various ATP and histone H1 concentrations, suggesting that p27 acts as a tight binding inhibitor of Cdk2/Cyclin E. We also found that p27 could be phosphorylated by Cdk2/Cyclin E only at high enzyme concentrations, and that p27 forms a stable interaction with Cdk2/Cyclin E regardless of its phosphorylation state. Adenosine Triphosphate 115-118 cyclin dependent kinase 2 Homo sapiens 207-211 10652602-6 1999 In addition, lovastatin increased the protein level of the cyclin-dependent kinase inhibitor (CDKI), p27, and markedly enhanced the binding of p27 with CDK2 and CDK4 more than CDK6 after 24 h exposure. Lovastatin 13-23 cyclin dependent kinase 2 Homo sapiens 152-156 10373534-6 1999 This cellular kinase activity is sensitive to transfection of a dominant negative form of CDK2 as well as the application of the CDK inhibitors p21 and butyrolactone I but not p16. 4-Butyrolactone 152-165 cyclin dependent kinase 2 Homo sapiens 90-94 10465404-3 1999 Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 microM, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. (2r)-pyrrolidin-2-yl-methanol 162-191 cyclin dependent kinase 2 Homo sapiens 51-55 10465404-3 1999 Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 microM, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. -iodobenzylamino 222-238 cyclin dependent kinase 2 Homo sapiens 51-55 10465404-3 1999 Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 microM, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. purine 263-269 cyclin dependent kinase 2 Homo sapiens 51-55 10375610-7 1999 Furthermore, stable expression of an antisense Cdk2 construct in NCI-H358 also resulted in the appearance of a marker of mucinous differentiation. ZINC78587988 69-73 cyclin dependent kinase 2 Homo sapiens 47-51 10377442-5 1999 Silibinin-induced G1 arrest was associated with a marked decrease in the kinase activity of cyclin-dependent kinases (CDKs) and associated cyclins because of a highly significant decrease in cyclin D1, CDK4, and CDK6 levels and an induction of Cip1/p21 and Kip1/p27 followed by their increased binding with CDK2. Silybin 0-9 cyclin dependent kinase 2 Homo sapiens 118-122 10377442-5 1999 Silibinin-induced G1 arrest was associated with a marked decrease in the kinase activity of cyclin-dependent kinases (CDKs) and associated cyclins because of a highly significant decrease in cyclin D1, CDK4, and CDK6 levels and an induction of Cip1/p21 and Kip1/p27 followed by their increased binding with CDK2. Silybin 0-9 cyclin dependent kinase 2 Homo sapiens 307-311 10392902-8 1999 In addition, CDK2 kinase activity was decreased in DXM-treated cells: we suggest that p27Kip1 might participate in inhibiting its catalytic activity. Dexamethasone 51-54 cyclin dependent kinase 2 Homo sapiens 13-17 10362524-4 1999 Based on this structural inference, a 3-dimensional model of the Cdk5-Nck5a*-ATP complex was derived from the X-ray structure of Cdk2-cyclinA-ATP complex. Adenosine Triphosphate 77-80 cyclin dependent kinase 2 Homo sapiens 129-133 10362524-4 1999 Based on this structural inference, a 3-dimensional model of the Cdk5-Nck5a*-ATP complex was derived from the X-ray structure of Cdk2-cyclinA-ATP complex. Adenosine Triphosphate 142-145 cyclin dependent kinase 2 Homo sapiens 129-133 10366423-3 1999 Rb phosphorylation, cyclin D1 expression, and cdk2 activation in G1 progression were all inhibited by NA22598, but the amounts of cdk2 and p27 were not affected. na22598 102-109 cyclin dependent kinase 2 Homo sapiens 46-50 10366423-5 1999 p27 binding to cdk2 was more markedly increased in suspension cultures than in attached cultures by NA22598, but the compound had no effect on total p27. na22598 100-107 cyclin dependent kinase 2 Homo sapiens 15-19 10363974-5 1999 Molecular modeling indicates that kenpaullone can bind in the ATP binding site of CDK2 with residue contacts similar to those observed in the crystal structures of other CDK2-bound inhibitors. kenpaullone 34-45 cyclin dependent kinase 2 Homo sapiens 82-86 10363974-5 1999 Molecular modeling indicates that kenpaullone can bind in the ATP binding site of CDK2 with residue contacts similar to those observed in the crystal structures of other CDK2-bound inhibitors. kenpaullone 34-45 cyclin dependent kinase 2 Homo sapiens 170-174 10363974-5 1999 Molecular modeling indicates that kenpaullone can bind in the ATP binding site of CDK2 with residue contacts similar to those observed in the crystal structures of other CDK2-bound inhibitors. Adenosine Triphosphate 62-65 cyclin dependent kinase 2 Homo sapiens 82-86 10363974-5 1999 Molecular modeling indicates that kenpaullone can bind in the ATP binding site of CDK2 with residue contacts similar to those observed in the crystal structures of other CDK2-bound inhibitors. Adenosine Triphosphate 62-65 cyclin dependent kinase 2 Homo sapiens 170-174 10454206-7 1999 The benzodiazepine derivative NSC 664704 (7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one) was revealed by that approach as a moderately potent (IC50 0.4 microM) inhibitor of CDK2, which in initial experiments shows evidence of causing cell cycle redistribution in living cells. 7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5h)-one 42-91 cyclin dependent kinase 2 Homo sapiens 177-181 10559866-3 1999 The crystal structure of CDK2 in complex with indirubin derivatives shows that indirubin interacts with the kinase"s ATP-binding site through van der Waals interactions and three hydrogen bonds. indirubin 46-55 cyclin dependent kinase 2 Homo sapiens 25-29 10559866-3 1999 The crystal structure of CDK2 in complex with indirubin derivatives shows that indirubin interacts with the kinase"s ATP-binding site through van der Waals interactions and three hydrogen bonds. Adenosine Triphosphate 117-120 cyclin dependent kinase 2 Homo sapiens 25-29 10559866-3 1999 The crystal structure of CDK2 in complex with indirubin derivatives shows that indirubin interacts with the kinase"s ATP-binding site through van der Waals interactions and three hydrogen bonds. Hydrogen 179-187 cyclin dependent kinase 2 Homo sapiens 25-29 10403550-6 1999 Overall these results indicate that vesnarinone inhibits the growth of gastric cancer cells by down-regulating G1 cyclins and CDK2 to induce G0-G1 arrest through a pathway different from that of cyclin inactivation by p21(Waf1/Cip1) or p27Kip1. vesnarinone 36-47 cyclin dependent kinase 2 Homo sapiens 126-130 10401624-6 1999 Cyclins B and E, and protein kinase CDK2 and CDK4 expressions were not affected by HNE, whereas DMSO induced an increase of cyclin E, B, and CDK2 from 8 h to 1 day. Dimethyl Sulfoxide 96-100 cyclin dependent kinase 2 Homo sapiens 141-145 16127615-4 1999 There is a lot of interest in targeting cyclin-dependent kinases (cdk): flavopiridol (Hoechst AG), a broad-spectrum inhibitor of cdk1, cdk2 and cdk4 is now entering phase II trials. alvocidib 72-84 cyclin dependent kinase 2 Homo sapiens 135-139 16127615-4 1999 There is a lot of interest in targeting cyclin-dependent kinases (cdk): flavopiridol (Hoechst AG), a broad-spectrum inhibitor of cdk1, cdk2 and cdk4 is now entering phase II trials. hoechst ag 86-96 cyclin dependent kinase 2 Homo sapiens 135-139 10454204-6 1999 These structures have shown that molecules related to ATP can be accommodated in the ATP-binding site in a number of orientations, utilising interactions observed between CDK2 and its natural ligand, as well as novel interactions with CDK2 residues that lie both within and outside the active site cleft. Adenosine Triphosphate 54-57 cyclin dependent kinase 2 Homo sapiens 171-175 10454204-6 1999 These structures have shown that molecules related to ATP can be accommodated in the ATP-binding site in a number of orientations, utilising interactions observed between CDK2 and its natural ligand, as well as novel interactions with CDK2 residues that lie both within and outside the active site cleft. Adenosine Triphosphate 54-57 cyclin dependent kinase 2 Homo sapiens 235-239 10454204-6 1999 These structures have shown that molecules related to ATP can be accommodated in the ATP-binding site in a number of orientations, utilising interactions observed between CDK2 and its natural ligand, as well as novel interactions with CDK2 residues that lie both within and outside the active site cleft. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 171-175 10454204-6 1999 These structures have shown that molecules related to ATP can be accommodated in the ATP-binding site in a number of orientations, utilising interactions observed between CDK2 and its natural ligand, as well as novel interactions with CDK2 residues that lie both within and outside the active site cleft. Adenosine Triphosphate 85-88 cyclin dependent kinase 2 Homo sapiens 235-239 10454205-5 1999 Many have been co-crystallised with CDK2, and their atomic interactions with the kinase have been analysed in detail: all are located in the ATP-binding pocket of the enzyme. Adenosine Triphosphate 141-144 cyclin dependent kinase 2 Homo sapiens 36-40 10454206-4 1999 Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1, 2, and 4 as a competitive ATP site antagonist. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 185-189 10454206-4 1999 Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1, 2, and 4 as a competitive ATP site antagonist. Flavonoids 32-41 cyclin dependent kinase 2 Homo sapiens 185-189 10454206-7 1999 The benzodiazepine derivative NSC 664704 (7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one) was revealed by that approach as a moderately potent (IC50 0.4 microM) inhibitor of CDK2, which in initial experiments shows evidence of causing cell cycle redistribution in living cells. Benzodiazepines 4-18 cyclin dependent kinase 2 Homo sapiens 177-181 10454206-8 1999 NSC 664704 is, therefore, a candidate for further structural optimization, guided in part by understanding of the ATP-binding site in CDK2. Adenosine Triphosphate 114-117 cyclin dependent kinase 2 Homo sapiens 134-138 10094816-4 1999 In addition, RA had no effect on the levels of Bcl-XL; Bcl-XS; cyclins A, B, D1, D3, or E; or Rb1 expression but markedly down-modulated Cdk2 kinase activity and reduced Cdk4 expression. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 137-141 10226033-6 1999 Cdk2 activity was higher in HU-treated cells than in mimosine-treated cells. Hydroxyurea 28-30 cyclin dependent kinase 2 Homo sapiens 0-4 10226033-6 1999 Cdk2 activity was higher in HU-treated cells than in mimosine-treated cells. Mimosine 53-61 cyclin dependent kinase 2 Homo sapiens 0-4 10226033-7 1999 Remarkably, inhibition of the Cdk2 activity in HU-treated cells with butyrolactone I or roscovitine [6], or by expression of the Cdk inhibitor p21(Waf1/Cip1), blocked the continued centrosome duplication. 4-Butyrolactone 69-82 cyclin dependent kinase 2 Homo sapiens 30-34 10226033-7 1999 Remarkably, inhibition of the Cdk2 activity in HU-treated cells with butyrolactone I or roscovitine [6], or by expression of the Cdk inhibitor p21(Waf1/Cip1), blocked the continued centrosome duplication. Roscovitine 88-99 cyclin dependent kinase 2 Homo sapiens 30-34 10226033-8 1999 Moreover, overexpression of Cdk2 reversed the inhibition of centrosome duplication by mimosine treatment. Mimosine 86-94 cyclin dependent kinase 2 Homo sapiens 28-32 10200261-2 1999 Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Peptides 0-8 cyclin dependent kinase 2 Homo sapiens 83-87 10200261-2 1999 Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Peptides 0-8 cyclin dependent kinase 2 Homo sapiens 100-104 10094816-6 1999 Olomoucine, a potent p34(cdc2) and Cdk2 inhibitor, effectively blocked RA-mediated p34(cdc2) kinase activation and prevented RA-induced apoptosis. olomoucine 0-10 cyclin dependent kinase 2 Homo sapiens 35-39 10208280-5 1999 Treatment of all glioma cell lines with 100 microM suramin consistently increased expression of cyclin A and its cyclin-dependent kinase, cdk 2, to levels reached following the exposure to exogenous elastin-degradation products (kappa-elastin). Suramin 51-58 cyclin dependent kinase 2 Homo sapiens 138-143 10094816-6 1999 Olomoucine, a potent p34(cdc2) and Cdk2 inhibitor, effectively blocked RA-mediated p34(cdc2) kinase activation and prevented RA-induced apoptosis. Tretinoin 71-73 cyclin dependent kinase 2 Homo sapiens 35-39 10233583-7 1999 Western blots showed that the expression of cell cycle-dependent kinases (cdk2 and cdk4), cyclin D1 and p53 was significantly reduced, while WAF1 was increased, after BFA treatment. Brefeldin A 167-170 cyclin dependent kinase 2 Homo sapiens 74-78 9990288-3 1999 A sequence in the R2 protein at serine-20 matches a consensus sequence for p34cdc2 and CDK2 kinases. Serine 32-38 cyclin dependent kinase 2 Homo sapiens 87-91 10234573-7 1999 The extent of inhibition of Cdk2 activity by PD98059 and olomoucine was consistent with their effects on cell proliferation and cell cycle. olomoucine 57-67 cyclin dependent kinase 2 Homo sapiens 28-32 10096555-5 1999 A combination of I3C and tamoxifen also caused a more pronounced decrease in cyclin-dependent kinase (CDK) 2-specific enzymatic activity than either compound alone but had no effect on CDK2 protein expression. Tamoxifen 25-34 cyclin dependent kinase 2 Homo sapiens 102-105 10086343-7 1999 USA; 95: 6977-6982, 1998) that silicon phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in human epidermoid carcinoma cells A431. silicon phthalocyanine 31-53 cyclin dependent kinase 2 Homo sapiens 203-207 10095772-7 1999 Mutation of one of these residues (T524) to alanine diminished the ability of B-Myb to promote transcription of a reporter gene, suggesting that phosphorylation of B-Myb at this site is important for the regulation of its activity by cyclin A/Cdk2. Alanine 44-51 cyclin dependent kinase 2 Homo sapiens 243-247 10074476-5 1999 Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E-CDK2 activity, was increased in serum-starved p27(-/-) cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant-negative mutant, inhibited apoptosis. Roscovitine 187-198 cyclin dependent kinase 2 Homo sapiens 36-40 10047461-0 1999 Cyclin E-cdk2 activation is associated with cell cycle arrest and inhibition of DNA replication induced by the thymidylate synthase inhibitor Tomudex. raltitrexed 142-149 cyclin dependent kinase 2 Homo sapiens 9-13 10047461-5 1999 Tomudex treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and cdk2 protein expression and kinase activities 24 h after a 2-h exposure. raltitrexed 0-7 cyclin dependent kinase 2 Homo sapiens 101-105 10047461-11 1999 The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by Tomudex indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance. Parathion 240-244 cyclin dependent kinase 2 Homo sapiens 138-142 10195283-1 1999 The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has specificity for both ATP and GTP, shows significant amino acid sequence similarity to the cyclin-dependent kinase 2 (CDK2). Adenosine Triphosphate 99-102 cyclin dependent kinase 2 Homo sapiens 168-193 10195283-1 1999 The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has specificity for both ATP and GTP, shows significant amino acid sequence similarity to the cyclin-dependent kinase 2 (CDK2). Adenosine Triphosphate 99-102 cyclin dependent kinase 2 Homo sapiens 195-199 10195283-1 1999 The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has specificity for both ATP and GTP, shows significant amino acid sequence similarity to the cyclin-dependent kinase 2 (CDK2). Guanosine Triphosphate 107-110 cyclin dependent kinase 2 Homo sapiens 168-193 10195283-1 1999 The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has specificity for both ATP and GTP, shows significant amino acid sequence similarity to the cyclin-dependent kinase 2 (CDK2). Guanosine Triphosphate 107-110 cyclin dependent kinase 2 Homo sapiens 195-199 9922449-4 1999 To elucidate the molecular mechanisms responsible for Cdk/cyclin transport, we examined nuclear import of fluorescent Cdk2/cyclin E and Cdc2/cyclin B1 complexes in digitonin-permeabilized mammalian cells and also examined potential physical interactions between these Cdks, cyclins, and soluble import factors. Digitonin 164-173 cyclin dependent kinase 2 Homo sapiens 118-122 9989807-0 1999 A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2. Tyrosine 79-87 cyclin dependent kinase 2 Homo sapiens 109-113 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Phosphates 42-52 cyclin dependent kinase 2 Homo sapiens 90-115 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Phosphates 42-52 cyclin dependent kinase 2 Homo sapiens 117-121 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Phosphates 42-52 cyclin dependent kinase 2 Homo sapiens 228-232 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Threonine 58-67 cyclin dependent kinase 2 Homo sapiens 90-115 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Threonine 58-67 cyclin dependent kinase 2 Homo sapiens 117-121 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Tyrosine 75-83 cyclin dependent kinase 2 Homo sapiens 90-115 9989807-1 1999 The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 activity at the G1 to S phase transition of the mammalian cell division cycle. Tyrosine 75-83 cyclin dependent kinase 2 Homo sapiens 117-121 9989807-7 1999 Paradoxically, tyrosine phosphorylation of cdk2 increased considerably as cells entered S phase, and cdc25A overexpression potentiated rather than diminished this effect. Tyrosine 15-23 cyclin dependent kinase 2 Homo sapiens 43-47 9990305-6 1999 PDGF-BB, on the other hand, induced phosphorylation of Rb, consistent with its ability to activate CDKs. Rubidium 55-57 cyclin dependent kinase 2 Homo sapiens 99-103 10234573-6 1999 PD98059 also inhibited the kinase activity of Cdk2 in IGF-1 stimulated cells, although the inhibition by olomoucine was much greater. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 0-7 cyclin dependent kinase 2 Homo sapiens 46-50 10234573-6 1999 PD98059 also inhibited the kinase activity of Cdk2 in IGF-1 stimulated cells, although the inhibition by olomoucine was much greater. olomoucine 105-115 cyclin dependent kinase 2 Homo sapiens 46-50 10234573-7 1999 The extent of inhibition of Cdk2 activity by PD98059 and olomoucine was consistent with their effects on cell proliferation and cell cycle. 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one 45-52 cyclin dependent kinase 2 Homo sapiens 28-32 10085115-0 1999 Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. Threonine 30-39 cyclin dependent kinase 2 Homo sapiens 47-72 10085115-4 1999 Fluorescence measurements have shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. Adenosine Triphosphate 127-130 cyclin dependent kinase 2 Homo sapiens 91-95 10085115-4 1999 Fluorescence measurements have shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. Adenosine Diphosphate 162-165 cyclin dependent kinase 2 Homo sapiens 91-95 10085115-6 1999 The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. Adenosine Triphosphate 30-33 cyclin dependent kinase 2 Homo sapiens 64-68 10085115-6 1999 The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. Adenosine Triphosphate 30-33 cyclin dependent kinase 2 Homo sapiens 90-94 10096555-5 1999 A combination of I3C and tamoxifen also caused a more pronounced decrease in cyclin-dependent kinase (CDK) 2-specific enzymatic activity than either compound alone but had no effect on CDK2 protein expression. Tamoxifen 25-34 cyclin dependent kinase 2 Homo sapiens 185-189 10096555-6 1999 Importantly, treatment with I3C and tamoxifen ablated expression of the phosphorylated retinoblastoma protein (Rb), an endogenous substrate for the G1 CDKs, whereas either agent alone only partially inhibited endogenous Rb phosphorylation. Tamoxifen 36-45 cyclin dependent kinase 2 Homo sapiens 151-155 11601206-0 1999 [Study of the role of cyclin-dependent kinases (CDKs) in retinoic acid (RA) inducing HL-60 cell differentiation]. Tretinoin 57-70 cyclin dependent kinase 2 Homo sapiens 48-52 11601206-0 1999 [Study of the role of cyclin-dependent kinases (CDKs) in retinoic acid (RA) inducing HL-60 cell differentiation]. Tretinoin 72-74 cyclin dependent kinase 2 Homo sapiens 48-52 11601206-3 1999 Meanwhile, histone H1 kinase assay was used to observe the changes of CDK2 activities in HL-60 cells treatment with ATRA and AE. Tretinoin 116-120 cyclin dependent kinase 2 Homo sapiens 70-74 11601206-3 1999 Meanwhile, histone H1 kinase assay was used to observe the changes of CDK2 activities in HL-60 cells treatment with ATRA and AE. alanylglutamic acid 125-127 cyclin dependent kinase 2 Homo sapiens 70-74 11601206-6 1999 The activities of cyclin E/CDK2 and the amounts of cyclin D1/CDK4 complexes were decreased in ATRA- or AE-treated HL-60 cells. Tretinoin 94-98 cyclin dependent kinase 2 Homo sapiens 27-31 11601206-6 1999 The activities of cyclin E/CDK2 and the amounts of cyclin D1/CDK4 complexes were decreased in ATRA- or AE-treated HL-60 cells. alanylglutamic acid 103-105 cyclin dependent kinase 2 Homo sapiens 27-31 11601206-7 1999 CONCLUSION: The effects of RA on the proliferation and differentiation of HL-60 cells may be associated with significant decreases in the activities of CDKs. Tretinoin 27-29 cyclin dependent kinase 2 Homo sapiens 152-156 9918868-0 1999 Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex. Eicosapentaenoic Acid 0-21 cyclin dependent kinase 2 Homo sapiens 130-134 9918868-0 1999 Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex. Docosahexaenoic Acids 26-46 cyclin dependent kinase 2 Homo sapiens 130-134 9918868-3 1999 EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2 kinase activity without altering the amount of cyclin E and p27(kip1) proteins and cyclin dependent kinase activating kinase activity by growth stimulation. Eicosapentaenoic Acid 0-3 cyclin dependent kinase 2 Homo sapiens 45-49 9918868-3 1999 EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2 kinase activity without altering the amount of cyclin E and p27(kip1) proteins and cyclin dependent kinase activating kinase activity by growth stimulation. Eicosapentaenoic Acid 0-3 cyclin dependent kinase 2 Homo sapiens 62-66 9918868-3 1999 EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2 kinase activity without altering the amount of cyclin E and p27(kip1) proteins and cyclin dependent kinase activating kinase activity by growth stimulation. Docosahexaenoic Acids 8-11 cyclin dependent kinase 2 Homo sapiens 45-49 9918868-3 1999 EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2 kinase activity without altering the amount of cyclin E and p27(kip1) proteins and cyclin dependent kinase activating kinase activity by growth stimulation. Docosahexaenoic Acids 8-11 cyclin dependent kinase 2 Homo sapiens 62-66 10481784-3 1999 Gsp gene, that may play an important role in 40% of GH-producing tumor, activation of 10% of non-functioning tumors and 6% of corticotroph adenomas, produces cAMP, which stimulates cyclin D1 and D3 which later produce cdk2 and cdk4 respectively, and stimulates cell progression from G1 to S phase. Cyclic AMP 158-162 cyclin dependent kinase 2 Homo sapiens 218-222 9819444-7 1998 In vitro, in the presence of ATP, the bound protein is folded and released in order to become associated with Cdk2. Adenosine Triphosphate 29-32 cyclin dependent kinase 2 Homo sapiens 110-114 9858588-3 1999 Tryptic phosphopeptide mapping revealed a family of p68 peptides that was modified well by cyclin A/cdk2 and poorly by cyclin E/cdk2. Peptides 56-64 cyclin dependent kinase 2 Homo sapiens 100-104 9858588-3 1999 Tryptic phosphopeptide mapping revealed a family of p68 peptides that was modified well by cyclin A/cdk2 and poorly by cyclin E/cdk2. Peptides 56-64 cyclin dependent kinase 2 Homo sapiens 128-132 9848777-6 1998 Treatment with lovastatin revealed the increment of both CDK2- and CDK4-bound-p27Kip1. Lovastatin 15-25 cyclin dependent kinase 2 Homo sapiens 57-61 9848777-8 1998 Lovastatin reduced both platelet-derived growth factor-stimulated CDK2 and CDK4 kinase activities. Lovastatin 0-10 cyclin dependent kinase 2 Homo sapiens 66-70 10036778-5 1998 Mutational analysis indicated that R2 phosphorylated the threonine residue within the T-loop of CDK2 and Cdc2Os1. Threonine 57-66 cyclin dependent kinase 2 Homo sapiens 96-100 9828096-9 1998 Concomitantly, CDK2, but not CDK4, activity immunoprecipitated from cells treated with olomoucine or roscovitine was markedly inhibited. Roscovitine 101-112 cyclin dependent kinase 2 Homo sapiens 15-19 9828096-10 1998 These results suggest that in normal cells, CDK2 kinase activity is the specific target of olomoucine and roscovitine. olomoucine 91-101 cyclin dependent kinase 2 Homo sapiens 44-48 9828096-0 1998 The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by specific inhibition of CDK2 kinase activity. olomoucine 39-49 cyclin dependent kinase 2 Homo sapiens 129-133 9828096-10 1998 These results suggest that in normal cells, CDK2 kinase activity is the specific target of olomoucine and roscovitine. Roscovitine 106-117 cyclin dependent kinase 2 Homo sapiens 44-48 9828096-0 1998 The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by specific inhibition of CDK2 kinase activity. Roscovitine 54-65 cyclin dependent kinase 2 Homo sapiens 129-133 9811471-0 1998 Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53. Lovastatin 0-10 cyclin dependent kinase 2 Homo sapiens 88-92 9828096-2 1998 Effects on the cell cycle were compared with those induced by the kinase inhibitor staurosporine, which arrests normal cells in early G1 phase by acting upstream of CDK2. Staurosporine 83-96 cyclin dependent kinase 2 Homo sapiens 165-169 9828096-9 1998 Concomitantly, CDK2, but not CDK4, activity immunoprecipitated from cells treated with olomoucine or roscovitine was markedly inhibited. olomoucine 87-97 cyclin dependent kinase 2 Homo sapiens 15-19 9891485-0 1998 Suppression of albumin and alpha-fetoprotein gene expression by butyrolactone I, a selective inhibitor of the cdk family, in HuH-7 human hepatoma cells. 4-Butyrolactone 64-77 cyclin dependent kinase 2 Homo sapiens 110-113 9814966-6 1998 Treatment of the CDK immune complexes with the detergent deoxycholate (DOC) resulted in restoration of CDK2, but not CDK4, activity at day 3 postconfluency, suggesting the presence of inhibitory protein(s) binding to the cyclin/CDK2 complex at this time point. Deoxycholic Acid 57-69 cyclin dependent kinase 2 Homo sapiens 103-107 9814966-6 1998 Treatment of the CDK immune complexes with the detergent deoxycholate (DOC) resulted in restoration of CDK2, but not CDK4, activity at day 3 postconfluency, suggesting the presence of inhibitory protein(s) binding to the cyclin/CDK2 complex at this time point. Deoxycholic Acid 57-69 cyclin dependent kinase 2 Homo sapiens 228-232 9814966-6 1998 Treatment of the CDK immune complexes with the detergent deoxycholate (DOC) resulted in restoration of CDK2, but not CDK4, activity at day 3 postconfluency, suggesting the presence of inhibitory protein(s) binding to the cyclin/CDK2 complex at this time point. Deoxycholic Acid 71-74 cyclin dependent kinase 2 Homo sapiens 103-107 9814966-6 1998 Treatment of the CDK immune complexes with the detergent deoxycholate (DOC) resulted in restoration of CDK2, but not CDK4, activity at day 3 postconfluency, suggesting the presence of inhibitory protein(s) binding to the cyclin/CDK2 complex at this time point. Deoxycholic Acid 71-74 cyclin dependent kinase 2 Homo sapiens 228-232 9811471-4 1998 However, the binding of p21 and p27 to CDK2 increases significantly following treatment of cells with lovastatin leading to inhibition of CDK2 activity and a subsequent arrest of cells in G1. Lovastatin 102-112 cyclin dependent kinase 2 Homo sapiens 39-43 9811471-4 1998 However, the binding of p21 and p27 to CDK2 increases significantly following treatment of cells with lovastatin leading to inhibition of CDK2 activity and a subsequent arrest of cells in G1. Lovastatin 102-112 cyclin dependent kinase 2 Homo sapiens 138-142 9811471-5 1998 The increased CKI binding to CDK2 is achieved by the redistribution of both p21 and p27 from CDK4 to CDK2 complexes subsequent to decreases in CDK4 and cyclin D3 expression following lovastatin treatment. Lovastatin 183-193 cyclin dependent kinase 2 Homo sapiens 29-33 9811471-5 1998 The increased CKI binding to CDK2 is achieved by the redistribution of both p21 and p27 from CDK4 to CDK2 complexes subsequent to decreases in CDK4 and cyclin D3 expression following lovastatin treatment. Lovastatin 183-193 cyclin dependent kinase 2 Homo sapiens 101-105 9811471-6 1998 Lastly, we show that lovastatin treatment of 76N-E6 breast cell line with an altered p53 pathway also results in G1 arrest and similar redistribution of CKIs from CDK4 to CDK2 as observed in other breast cell lines examined. Lovastatin 21-31 cyclin dependent kinase 2 Homo sapiens 171-175 9811471-7 1998 These observations suggest that lovastatin induced G1 arrest of breast cell lines is through a p53 independent pathway and is mediated by decreased CDK2 activity through redistribution of CKIs from CDK4 to CDK2. Lovastatin 32-42 cyclin dependent kinase 2 Homo sapiens 148-152 9811471-7 1998 These observations suggest that lovastatin induced G1 arrest of breast cell lines is through a p53 independent pathway and is mediated by decreased CDK2 activity through redistribution of CKIs from CDK4 to CDK2. Lovastatin 32-42 cyclin dependent kinase 2 Homo sapiens 206-210 9891485-1 1998 Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family, cdk2 and cdc2 kinase. butyrolactone I 0-15 cyclin dependent kinase 2 Homo sapiens 73-76 9891485-1 1998 Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family, cdk2 and cdc2 kinase. butyrolactone I 0-15 cyclin dependent kinase 2 Homo sapiens 86-90 9716179-10 1998 RXR-gamma expression produced significant reduction in levels of RA-responsive genes including the cyclin-dependent kinase inhibitors p21Cip1/WAF1 and p27Kip1, resulting in increased cdc2 and cdk2 kinase activity and RB phosphorylation. Tretinoin 65-67 cyclin dependent kinase 2 Homo sapiens 192-196 9829836-12 1998 Hybrid proteins in which more than two-thirds of the molecule were derived from human Cdk2 retained Pho85p function with respect to high-phosphate repression of the PHO5 promoter. Phosphates 137-146 cyclin dependent kinase 2 Homo sapiens 86-90 9705214-9 1998 For example, TCDD significantly inhibited E2-induced hyperphosphorylation of RB, cyclin D1 protein, and cdk2-, cdk4-, and cdk7-dependent kinase activities. Polychlorinated Dibenzodioxins 13-17 cyclin dependent kinase 2 Homo sapiens 104-108 9705214-10 1998 Inhibition of E2-induced cdk4-dependent kinase activity by TCDD may be related to the parallel decrease of E2-induced cyclin D1 protein, and inhibition of induced cdk2- and cdk4-dependent kinase activities may be due to significantly increased p21 levels in cells cotreated with TCDD plus E2. Polychlorinated Dibenzodioxins 59-63 cyclin dependent kinase 2 Homo sapiens 163-167 9802881-4 1998 Exposure of HNSCC cells to flavopiridol diminished cdc2 and cdk2 activity and potently inhibited cell proliferation (IC50 43-83 nM), which was concomitant with the appearance of cells with a sub-G1 DNA content. alvocidib 27-39 cyclin dependent kinase 2 Homo sapiens 60-64 9784625-6 1998 Linoleic acid induced depletion of p27kip1 and increased CDK2 activity, events required for G1/S transition. Linoleic Acid 0-13 cyclin dependent kinase 2 Homo sapiens 57-61 9784625-8 1998 These findings suggest that in addition to inducing immediate early growth response events, linoleic acid mimics growth factors in activating cell cycle events that are associated with G1/S transition in SMC and the negative regulation of linoleic acid-induced growth by cAMP is apparently due to its antagonism with linoleic acid-induced p27kip1 depletion and CDK2 activation. Linoleic Acid 92-105 cyclin dependent kinase 2 Homo sapiens 361-365 9784625-8 1998 These findings suggest that in addition to inducing immediate early growth response events, linoleic acid mimics growth factors in activating cell cycle events that are associated with G1/S transition in SMC and the negative regulation of linoleic acid-induced growth by cAMP is apparently due to its antagonism with linoleic acid-induced p27kip1 depletion and CDK2 activation. Linoleic Acid 239-252 cyclin dependent kinase 2 Homo sapiens 361-365 9784625-8 1998 These findings suggest that in addition to inducing immediate early growth response events, linoleic acid mimics growth factors in activating cell cycle events that are associated with G1/S transition in SMC and the negative regulation of linoleic acid-induced growth by cAMP is apparently due to its antagonism with linoleic acid-induced p27kip1 depletion and CDK2 activation. Linoleic Acid 239-252 cyclin dependent kinase 2 Homo sapiens 361-365 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. Tretinoin 20-22 cyclin dependent kinase 2 Homo sapiens 146-150 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. Tretinoin 20-22 cyclin dependent kinase 2 Homo sapiens 152-156 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. dextramycine 31-34 cyclin dependent kinase 2 Homo sapiens 146-150 9778049-3 1998 Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. dextramycine 31-34 cyclin dependent kinase 2 Homo sapiens 152-156 9778049-5 1998 In addition, RA-treated LCLs showed a marked up-regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level, which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 190-194 9778049-5 1998 In addition, RA-treated LCLs showed a marked up-regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level, which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2. Tretinoin 13-15 cyclin dependent kinase 2 Homo sapiens 284-288 9778049-9 1998 Overall, these results demonstrate that RA treatment of EBV-immortalized B lymphocytes is associated with multiple effects on G1 regulatory proteins, including p27Kip1 up-regulation, decreased levels of cyclins D2, D3 and A, and inhibition of CDK2, CDK4 and CDK6 activity, which ultimately result in reduced pRb phosphorylation and G0/G1 growth arrest. Tretinoin 40-42 cyclin dependent kinase 2 Homo sapiens 243-247 9725911-2 1998 Cdk activation requires phosphorylation of a key residue (on sites equivalent to Thr-160 in human cdk2) carried out by the cdk-activating kinase (CAK). Threonine 81-84 cyclin dependent kinase 2 Homo sapiens 98-102 9677190-1 1998 Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). 2,6,9-trisubstituted purines 98-126 cyclin dependent kinase 2 Homo sapiens 183-208 9664138-7 1998 Genistein induced expression of p21, and the increased levels of p21 were associated with increased binding of p21 with cdc2 and cdk2. Genistein 0-9 cyclin dependent kinase 2 Homo sapiens 129-133 9664138-8 1998 These observations suggest that genistein induces a G2/M arrest in human breast cancer cells, the mechanism of which is in part due to inhibition of kinase activities of cdc2 and cdk2, and decrease in cyclin B1 expression. Genistein 32-41 cyclin dependent kinase 2 Homo sapiens 179-183 9677190-1 1998 Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). 2,6,9-trisubstituted purines 98-126 cyclin dependent kinase 2 Homo sapiens 210-214 9677190-1 1998 Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). Adenosine Triphosphate 134-156 cyclin dependent kinase 2 Homo sapiens 183-208 9677190-1 1998 Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). Adenosine Triphosphate 134-156 cyclin dependent kinase 2 Homo sapiens 210-214 9639406-1 1998 The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). alvocidib 20-32 cyclin dependent kinase 2 Homo sapiens 84-88 9632724-5 1998 Site-directed mutagenesis identified phenylalanine 79 and tyrosine 80 within the 3(10) helix region of p57 as crucial residues for kinase inhibition, supporting the structural evidence that the 3(10) helix binds deep inside the catalytic cleft of Cdk2, mimicking ATP. Phenylalanine 37-50 cyclin dependent kinase 2 Homo sapiens 247-251 9703866-0 1998 Treatment of human glioblastoma cells with the staurosporine derivative CGP 41251 inhibits CDC2 and CDK2 kinase activity and increases radiation sensitivity. Staurosporine 47-60 cyclin dependent kinase 2 Homo sapiens 100-104 9632724-5 1998 Site-directed mutagenesis identified phenylalanine 79 and tyrosine 80 within the 3(10) helix region of p57 as crucial residues for kinase inhibition, supporting the structural evidence that the 3(10) helix binds deep inside the catalytic cleft of Cdk2, mimicking ATP. Tyrosine 58-66 cyclin dependent kinase 2 Homo sapiens 247-251 9560221-1 1998 The activation of cyclin-dependent kinases (CDKs) requires phosphorylation of a threonine residue within the T-loop catalyzed by CDK-activating kinases (CAKs). Threonine 80-89 cyclin dependent kinase 2 Homo sapiens 44-48 9637776-0 1998 Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase. Tyrphostins 42-53 cyclin dependent kinase 2 Homo sapiens 14-18 9637776-11 1998 Further analysis revealed that these tyrphostins act by inhibiting the activation of the enzyme Cdk2 without affecting its levels or its intrinsic kinase activity. Tyrphostins 37-48 cyclin dependent kinase 2 Homo sapiens 96-100 9637776-14 1998 These compounds lead to the accumulation of phosphorylated Cdk2 on tyrosine 15 which is most probably the cause for its inhibition leading to cell cycle arrest at G1/S. Tyrosine 67-75 cyclin dependent kinase 2 Homo sapiens 59-63 9637776-15 1998 A structure-activity relationship study defines a very precise pharmacophore, suggesting a unique molecular target not yet identified and which is most probably involved in the regulation of the tyrosine-phosphorylated state of Cdk2. Tyrosine 195-203 cyclin dependent kinase 2 Homo sapiens 228-232 9618490-2 1998 We find that the Fas-induced activation of cdc2 and cdk2 in Jurkat cells is not dependent on protein synthesis, which is shut down very early during apoptosis before caspase-3 activation. ammonium ferrous sulfate 17-20 cyclin dependent kinase 2 Homo sapiens 52-56 18465538-4 1998 In ex vivo experiments with tumor cells from refractory chronic lymphoblastic leukemia, dose-dependent CDK2 inhibition associated with apoptotic changes was seen at concentrations greater than 100 nM of flavopiridol. alvocidib 203-215 cyclin dependent kinase 2 Homo sapiens 103-107 9581834-8 1998 In the studies analyzing cell cycle regulatory molecules, silymarin treatment of cells also resulted in a significant induction of cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip1/p27, concomitant with a significant decrease in CDK4 expression, but no change in the levels of CDK2 and CDK6 and their associated cyclins E and D1, respectively. Silymarin 58-67 cyclin dependent kinase 2 Homo sapiens 288-292 9581834-9 1998 Cells treated with silymarin also showed an increased binding of CDKIs with CDKs, together with a marked decrease in the kinase activity of CDKs and associated cyclins. Silymarin 19-28 cyclin dependent kinase 2 Homo sapiens 76-80 9615391-5 1998 Consistent with these results, bryostatin 1 was less effective in inducing G0/G1 arrest and inhibiting cyclin-dependent kinase 2 (CDK2) activity. bryostatin 1 31-43 cyclin dependent kinase 2 Homo sapiens 103-128 9615391-5 1998 Consistent with these results, bryostatin 1 was less effective in inducing G0/G1 arrest and inhibiting cyclin-dependent kinase 2 (CDK2) activity. bryostatin 1 31-43 cyclin dependent kinase 2 Homo sapiens 130-134 9615391-9 1998 Co-administration of bryostatin 1 with PMA antagonized the latter"s differentiation-inducing capacity and anti-proliferative effects, actions that were accompanied by a reduction in PMA-mediated p21CIP1/WAF1 induction, CDK2 inhibition, pRb dephosphorylation, and c-Myc downregulation. bryostatin 1 21-33 cyclin dependent kinase 2 Homo sapiens 219-223 9615391-9 1998 Co-administration of bryostatin 1 with PMA antagonized the latter"s differentiation-inducing capacity and anti-proliferative effects, actions that were accompanied by a reduction in PMA-mediated p21CIP1/WAF1 induction, CDK2 inhibition, pRb dephosphorylation, and c-Myc downregulation. Tetradecanoylphorbol Acetate 39-42 cyclin dependent kinase 2 Homo sapiens 219-223 9652739-0 1998 Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase. Calcitriol 62-86 cyclin dependent kinase 2 Homo sapiens 105-109 9581834-9 1998 Cells treated with silymarin also showed an increased binding of CDKIs with CDKs, together with a marked decrease in the kinase activity of CDKs and associated cyclins. Silymarin 19-28 cyclin dependent kinase 2 Homo sapiens 140-144 9560221-7 1998 Immunoprecipitates with the anti-Cak1At antibody phosphorylated human CDK2 at the threonine residue (T160) within the T-loop and activated its activity to phosphorylate histone H1. Threonine 82-91 cyclin dependent kinase 2 Homo sapiens 70-74 9560221-7 1998 Immunoprecipitates with the anti-Cak1At antibody phosphorylated human CDK2 at the threonine residue (T160) within the T-loop and activated its activity to phosphorylate histone H1. 2,2',2''-trichlorotriethylamine 101-105 cyclin dependent kinase 2 Homo sapiens 70-74 9486668-5 1998 p27Kip1 inhibited Cdk2 activity, suggesting that Kip CKIs promote G1 arrest in VSMCs by binding cyclin E/Cdk2. vsmcs 79-84 cyclin dependent kinase 2 Homo sapiens 18-22 9615715-1 1998 [2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylp urine] (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases cdc2 and cdk2. Roscovitine 0-70 cyclin dependent kinase 2 Homo sapiens 158-162 9492054-0 1998 Antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Calcitriol 28-57 cyclin dependent kinase 2 Homo sapiens 121-146 9553123-4 1998 Lovastatin treatment increased protein and mRNA levels of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), increased binding of p21 with Cdk2, markedly inhibited cyclin E- and Cdk2-associated phosphorylation of histone H1 or GST-retinoblastoma protein, enhanced binding of the retinoblastoma protein to the transcription factor E2F-1 in vivo, and induced the activation of a p21 promoter reporter construct. Lovastatin 0-10 cyclin dependent kinase 2 Homo sapiens 142-146 9553123-4 1998 Lovastatin treatment increased protein and mRNA levels of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), increased binding of p21 with Cdk2, markedly inhibited cyclin E- and Cdk2-associated phosphorylation of histone H1 or GST-retinoblastoma protein, enhanced binding of the retinoblastoma protein to the transcription factor E2F-1 in vivo, and induced the activation of a p21 promoter reporter construct. Lovastatin 0-10 cyclin dependent kinase 2 Homo sapiens 181-185 9563902-5 1998 The inhibitory effects of silymarin on cell growth and proliferation were associated with a G1 arrest in cell cycle progression concomitant with an induction of up to 19-fold in the protein expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21. Silymarin 26-35 cyclin dependent kinase 2 Homo sapiens 229-232 9615715-1 1998 [2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylp urine] (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases cdc2 and cdk2. Roscovitine 72-83 cyclin dependent kinase 2 Homo sapiens 158-162 9486668-5 1998 p27Kip1 inhibited Cdk2 activity, suggesting that Kip CKIs promote G1 arrest in VSMCs by binding cyclin E/Cdk2. vsmcs 79-84 cyclin dependent kinase 2 Homo sapiens 105-109 9488034-2 1998 The IPTG-induced wildtype p21 bound to CDK2 and PCNA and inhibited CDK activity in the cells and reduced cell growth rate; whereas, both IPTG-induced mutated p21 proteins neither bound to CDK2 nor affected the CDK activity but did bind to PCNA, and they did not affect the cell growth rate. Isopropyl Thiogalactoside 4-8 cyclin dependent kinase 2 Homo sapiens 39-43 9438871-0 1997 Structures of staurosporine bound to CDK2 and cAPK--new tools for structure-based design of protein kinase inhibitors. Staurosporine 14-27 cyclin dependent kinase 2 Homo sapiens 37-41 9498822-0 1998 G1 phase arrest by the phosphatidylinositol 3-kinase inhibitor LY 294002 is correlated to up-regulation of p27Kip1 and inhibition of G1 CDKs in choroidal melanoma cells. Phosphatidylinositols 23-43 cyclin dependent kinase 2 Homo sapiens 136-140 9498822-0 1998 G1 phase arrest by the phosphatidylinositol 3-kinase inhibitor LY 294002 is correlated to up-regulation of p27Kip1 and inhibition of G1 CDKs in choroidal melanoma cells. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 63-72 cyclin dependent kinase 2 Homo sapiens 136-140 9498822-5 1998 We report that the LY 294002-induced G1 arrest is closely correlated to inhibition of CDK4 and CDK2 activities leading to the impairment of pRb phosphorylation which normally occurs during G1 progression. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 19-28 cyclin dependent kinase 2 Homo sapiens 95-99 9521129-1 1998 The kinase associated phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates the cell cycle control protein, cyclin dependent kinase-2 on Thr 160 in a cyclin dependent manner (Poon & Hunter, 1995). Threonine 171-174 cyclin dependent kinase 2 Homo sapiens 142-167 9841966-2 1998 Transition from G1 to S phase of the cell cycle requires activation of cyclin-dependent kinase 2 (Cdk2) which is inhibited by olomoucine and roscovitine. olomoucine 126-136 cyclin dependent kinase 2 Homo sapiens 71-96 9841966-2 1998 Transition from G1 to S phase of the cell cycle requires activation of cyclin-dependent kinase 2 (Cdk2) which is inhibited by olomoucine and roscovitine. olomoucine 126-136 cyclin dependent kinase 2 Homo sapiens 98-102 9841966-2 1998 Transition from G1 to S phase of the cell cycle requires activation of cyclin-dependent kinase 2 (Cdk2) which is inhibited by olomoucine and roscovitine. Roscovitine 141-152 cyclin dependent kinase 2 Homo sapiens 71-96 9841966-2 1998 Transition from G1 to S phase of the cell cycle requires activation of cyclin-dependent kinase 2 (Cdk2) which is inhibited by olomoucine and roscovitine. Roscovitine 141-152 cyclin dependent kinase 2 Homo sapiens 98-102 9841966-3 1998 The purpose of this study was to determine whether olomoucine and roscovitine can block Cdk2 kinase activity and inhibit proliferation of four human pancreatic cancer cell lines with various genetic alterations. olomoucine 51-61 cyclin dependent kinase 2 Homo sapiens 88-92 9841966-3 1998 The purpose of this study was to determine whether olomoucine and roscovitine can block Cdk2 kinase activity and inhibit proliferation of four human pancreatic cancer cell lines with various genetic alterations. Roscovitine 66-77 cyclin dependent kinase 2 Homo sapiens 88-92 9841966-8 1998 Olomoucine and roscovitine blocked Cdk2 activity in all four pancreatic cancer cell lines. olomoucine 0-10 cyclin dependent kinase 2 Homo sapiens 35-39 9841966-8 1998 Olomoucine and roscovitine blocked Cdk2 activity in all four pancreatic cancer cell lines. Roscovitine 15-26 cyclin dependent kinase 2 Homo sapiens 35-39 9841966-10 1998 Roscovitine was at least threefold more potent than olomoucine for both Cdk2 activity and cell proliferation. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 72-76 9841966-10 1998 Roscovitine was at least threefold more potent than olomoucine for both Cdk2 activity and cell proliferation. olomoucine 52-62 cyclin dependent kinase 2 Homo sapiens 72-76 9438871-2 1997 The recently determined structures of two protein kinases, cAPK and CDK2, in complex with an inhibitor, staurosporine, provide a detailed account of inhibitor-kinase interactions and inhibitor selectivity. Staurosporine 104-117 cyclin dependent kinase 2 Homo sapiens 68-72 9372912-3 1997 Recently, cyclin E-Cdk2- and cyclin A-Cdk2-dependent phosphorylation of a single conserved serine residue (Ser5) in Id2 has been shown to occur during late G1-to-S phase transition of the cell cycle, and this neutralizes the function of Id2 in abrogating E-box-dependent bHLH homo- or heterodimer complex formation in vitro (E. Hara, M. Hall, and G. Peters, EMBO J. Serine 91-97 cyclin dependent kinase 2 Homo sapiens 38-42 9345026-0 1997 Complex regulation of CDK2 during phorbol ester-induced hematopoietic differentiation. Phorbol Esters 34-47 cyclin dependent kinase 2 Homo sapiens 22-26 9401001-3 1997 Both contact-inhibition and serum-deprivation led to a strong decrease of cdk4-kinase-activity and cdk2-phosphorylation at Thr 160, while the total amounts of cdk4 and cdk2 remained constant. Threonine 123-126 cyclin dependent kinase 2 Homo sapiens 99-103 9388487-4 1997 Although both cyclin D1- and cyclin-E-dependent kinases are active in the late G1 phase in human fibroblasts, cyclin E/Cdk2 specifically phosphorylates p27 on threonine-187 in vitro. Threonine 159-168 cyclin dependent kinase 2 Homo sapiens 119-123 9372912-3 1997 Recently, cyclin E-Cdk2- and cyclin A-Cdk2-dependent phosphorylation of a single conserved serine residue (Ser5) in Id2 has been shown to occur during late G1-to-S phase transition of the cell cycle, and this neutralizes the function of Id2 in abrogating E-box-dependent bHLH homo- or heterodimer complex formation in vitro (E. Hara, M. Hall, and G. Peters, EMBO J. Serine 91-97 cyclin dependent kinase 2 Homo sapiens 19-23 9399644-3 1997 We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. Threonine 72-81 cyclin dependent kinase 2 Homo sapiens 26-30 9399644-3 1997 We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. Valine 135-141 cyclin dependent kinase 2 Homo sapiens 26-30 9399644-3 1997 We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. Valine 135-141 cyclin dependent kinase 2 Homo sapiens 162-166 9399644-7 1997 After induction of Myc, p27 phosphorylated at threonine 187 transiently accumulates in a non cdk2 bound form. Threonine 46-55 cyclin dependent kinase 2 Homo sapiens 93-97 9345026-4 1997 In contrast, the level of cyclin E protein remains unchanged and in a complex with cdk2 during the entire course of PMA treatment. Tetradecanoylphorbol Acetate 116-119 cyclin dependent kinase 2 Homo sapiens 83-87 9345026-5 1997 During the PMA-induced differentiation, cyclin E-associated cdk2 activity drops markedly. Tetradecanoylphorbol Acetate 11-14 cyclin dependent kinase 2 Homo sapiens 60-64 9345026-6 1997 Furthermore, the amount of p27(Kip1) protein associated with cyclin E/cdk2 greatly increases 24 to 72 hours after PMA treatment. Tetradecanoylphorbol Acetate 114-117 cyclin dependent kinase 2 Homo sapiens 70-74 9366521-3 1997 RA-induced cell cycle arrest is also associated with induction of p27Kip1 expression, inhibition of cdk2-associated kinase activity and alteration of the phosphorylation state of the pRB-family proteins. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 100-104 21528311-3 1997 Rapamycin treatment also resulted in: a decrease in cdk2 kinase activity; an increase in hypophosphorylated retinoblastoma protein (pRb); a dephosphorylation of p70 S6 kinase; and, growth-arrest in G(1)-phase of cell cycle. Sirolimus 0-9 cyclin dependent kinase 2 Homo sapiens 52-56 9328342-7 1997 The activity of the cell cycle-dependent protein kinase, cdk2, is regulated biphasically by progesterone: it increases initially, then decreases. Progesterone 92-104 cyclin dependent kinase 2 Homo sapiens 57-61 9344580-5 1997 Similarly, roscovitine, another CDK inhibitor with a 10-fold higher efficiency for both CDK1 and CDK2 as compared to olomoucine, showed the same effects at a 10-fold lower concentration. Roscovitine 11-22 cyclin dependent kinase 2 Homo sapiens 97-101 9380407-2 1997 EB1089 treatment of the breast cancer cell lines MCF-7 E, BT20, T47D, and ZR75 demonstrated a correlation between a reduction in Cdk2 kinase activity towards phosphorylation of histone H1 and a decrease in DNA synthesis, while no modulation of Cdk2 activity was observed in the vitamin D3 and EB1089 resistant cell line MCF-7 L. This was accompanied by a time dependent decrease in the percentage of S phase cells in the responsive lines. Cholecalciferol 278-288 cyclin dependent kinase 2 Homo sapiens 129-133 9334743-0 1997 Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Staurosporine 29-42 cyclin dependent kinase 2 Homo sapiens 97-101 9334743-2 1997 The structure of a CDK2 staurosporine complex explains the tight binding of this inhibitor, and suggests features to be exploited in the design of specific inhibitors of CDKs. Staurosporine 24-37 cyclin dependent kinase 2 Homo sapiens 19-23 9334743-2 1997 The structure of a CDK2 staurosporine complex explains the tight binding of this inhibitor, and suggests features to be exploited in the design of specific inhibitors of CDKs. Staurosporine 24-37 cyclin dependent kinase 2 Homo sapiens 170-174 9294607-5 1997 We report here that exposure of human epithelial cells to ethanol, at concentration (100-200 mM) that do not cause cell death, (a) does not affect or only reduces slightly the cellular level of p53 protein, (b) upregulates the transcription of the WAF1/CIP1 gene, (c) inhibits the Cdk2 activity, and (d) reduces the rate of cellular proliferation by inducing a delay in G1 phase transition. Ethanol 58-65 cyclin dependent kinase 2 Homo sapiens 281-285 9294175-3 1997 ER is phosphorylated between amino acids 82 and 121 in vitro by the cyclin A/cdk2 complex and incorporation of phosphate into ER is stimulated by ectopic expression of cyclin A in vivo. Phosphates 111-120 cyclin dependent kinase 2 Homo sapiens 77-81 9298898-4 1997 The conformation of the P+1 pocket is similar to a second proline-directed kinase, CDK2-CyclinA, thus permitting the origin of this specificity to be defined. Proline 58-65 cyclin dependent kinase 2 Homo sapiens 83-87 9271412-3 1997 We found that delaying the expression of Ras(Asn17) until late in the G1 phase by introducing dexamethasone 3 h after the addition of epidermal growth factor (EGF) abolished the downregulation of the p27kip1 cyclin-dependent kinase (CDK) inhibitor which normally occurred during this period, with resultant suppression of cyclin Ds/CDK4 and cyclin E/CDK2 and G1 arrest. Dexamethasone 94-107 cyclin dependent kinase 2 Homo sapiens 350-354 9288782-4 1997 AG 1478 induces a massive increase in the Cdk2 protein inhibitors p27 and p21, whereas AG 555 appears to have a different mechanism of action, inhibiting the activation of Cdk2. RTKI cpd 0-7 cyclin dependent kinase 2 Homo sapiens 42-46 9275052-7 1997 By contrast, differences in the activity of cyclin E-CDK2 complexes were found, with a profound decrease in the extracts of cells growth arrested by dexamethasone. Dexamethasone 149-162 cyclin dependent kinase 2 Homo sapiens 53-57 9258408-0 1997 G1 phase arrest of human smooth muscle cells by heparin, IL-4 and cAMP is linked to repression of cyclin D1 and cdk2. Heparin 48-55 cyclin dependent kinase 2 Homo sapiens 112-116 9258408-0 1997 G1 phase arrest of human smooth muscle cells by heparin, IL-4 and cAMP is linked to repression of cyclin D1 and cdk2. Cyclic AMP 66-70 cyclin dependent kinase 2 Homo sapiens 112-116 9258408-6 1997 Heparin, a strong inhibitor of HUASMC proliferation, strongly down-modulated the levels of cyclin D1 mRNA and protein, cdk2 mRNA and cdc2 protein. Heparin 0-7 cyclin dependent kinase 2 Homo sapiens 119-123 9259311-0 1997 CDK2 is a target for retinoic acid-mediated growth inhibition in MCF-7 human breast cancer cells. Tretinoin 21-34 cyclin dependent kinase 2 Homo sapiens 0-4 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 47-49 cyclin dependent kinase 2 Homo sapiens 65-69 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 90-92 cyclin dependent kinase 2 Homo sapiens 19-23 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 47-49 cyclin dependent kinase 2 Homo sapiens 237-241 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 90-92 cyclin dependent kinase 2 Homo sapiens 117-121 9259311-6 1997 While cdk4 activity was similar in control and RA-treated cells, cdk2 activity began to decrease within 48 h of exposure to RA and was profoundly reduced after 72 h. This reduced activity was associated with decreased phosphorylation of cdk2. Tretinoin 124-126 cyclin dependent kinase 2 Homo sapiens 65-69 9259311-9 1997 Our results show that RA inhibits cell cycle progression of MCF-7 cells by inhibiting cdk2 mRNA and protein production and by decreasing cdk2 activity. Tretinoin 22-24 cyclin dependent kinase 2 Homo sapiens 86-90 9259311-8 1997 However, assays of cdk2 from pooled lysates from RA-treated and control cells showed that RA-treated cells contain a cdk2-inhibitory activity. Tretinoin 49-51 cyclin dependent kinase 2 Homo sapiens 19-23 9259311-9 1997 Our results show that RA inhibits cell cycle progression of MCF-7 cells by inhibiting cdk2 mRNA and protein production and by decreasing cdk2 activity. Tretinoin 22-24 cyclin dependent kinase 2 Homo sapiens 137-141 9300578-1 1997 We have studied the effects of olomoucine, a selective inhibitor of cdk2, cdc2 and MAP kinase, on the rate of proliferation and the cell cycle progression in human cancer cells in culture. olomoucine 31-41 cyclin dependent kinase 2 Homo sapiens 68-72 9288122-1 1997 BACKGROUND: Olomoucine and roscovitine are novel compounds that are designed to inhibit cyclin-dependent kinases (e.g., Cdk2 and cdc2). olomoucine 12-22 cyclin dependent kinase 2 Homo sapiens 120-124 9288122-1 1997 BACKGROUND: Olomoucine and roscovitine are novel compounds that are designed to inhibit cyclin-dependent kinases (e.g., Cdk2 and cdc2). Roscovitine 27-38 cyclin dependent kinase 2 Homo sapiens 120-124 9288122-3 1997 The purpose of this study was to determine (1) whether olomoucine and roscovitine inhibit Cdk2 and cdc2 kinase activities of the human gastric cancer cell line SIIA and (2) whether olomoucine and roscovitine block cell proliferation and cell cycle progression. olomoucine 55-65 cyclin dependent kinase 2 Homo sapiens 90-94 9288122-3 1997 The purpose of this study was to determine (1) whether olomoucine and roscovitine inhibit Cdk2 and cdc2 kinase activities of the human gastric cancer cell line SIIA and (2) whether olomoucine and roscovitine block cell proliferation and cell cycle progression. Roscovitine 70-81 cyclin dependent kinase 2 Homo sapiens 90-94 9288122-7 1997 RESULTS: Olomoucine and roscovitine completely blocked Cdk2 and cdc2 activities in SIIA cells. olomoucine 9-19 cyclin dependent kinase 2 Homo sapiens 55-59 9288122-7 1997 RESULTS: Olomoucine and roscovitine completely blocked Cdk2 and cdc2 activities in SIIA cells. Roscovitine 24-35 cyclin dependent kinase 2 Homo sapiens 55-59 9230188-6 1997 These data show that the functions of Cdk4 and Cdk6 are not redundant and that Cdk6 and Cdk2 activities are regulated by 1,25-dihydroxyvitamin D3. Calcitriol 121-145 cyclin dependent kinase 2 Homo sapiens 88-92 9233783-8 1997 Retinoids were also found to inhibit the expression levels of other cell cycle related proteins, including Cdk2 and Cdk4, resulting in lower kinase activities. Retinoids 0-9 cyclin dependent kinase 2 Homo sapiens 107-111 9199341-2 1997 Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. Estradiol 12-21 cyclin dependent kinase 2 Homo sapiens 125-129 9199341-2 1997 Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. Estradiol 12-21 cyclin dependent kinase 2 Homo sapiens 272-276 9199341-2 1997 Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. Tamoxifen 63-72 cyclin dependent kinase 2 Homo sapiens 125-129 9199341-2 1997 Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. Tamoxifen 63-72 cyclin dependent kinase 2 Homo sapiens 272-276 9210954-14 1997 In conclusion, apigenin treatment produced a G1 cell-cycle arrest by inhibiting cdk2 kinase activity and the phosphorylation of Rb and inducing the cdk inhibitor p21/WAF1, all of which may mediate its chemopreventive activities in vivo. Apigenin 15-23 cyclin dependent kinase 2 Homo sapiens 80-84 9237626-0 1997 Tyrphostin AG 494 blocks Cdk2 activation. Tyrphostins 0-10 cyclin dependent kinase 2 Homo sapiens 25-29 9237626-7 1997 AG 494 exerts its full inhibitory activity on Cdk2 activation even when added 20 h subsequent to EGF addition when Cdk2 activation is maximal. AG 494 0-6 cyclin dependent kinase 2 Homo sapiens 46-50 9237626-7 1997 AG 494 exerts its full inhibitory activity on Cdk2 activation even when added 20 h subsequent to EGF addition when Cdk2 activation is maximal. AG 494 0-6 cyclin dependent kinase 2 Homo sapiens 115-119 9210954-12 1997 Inhibition of cdk2 kinase activity in apigenin-treated cells was associated with the accumulation of the hypophosphorylated form of the retinoblastoma (Rb) protein as measured by western blot analysis. Apigenin 38-46 cyclin dependent kinase 2 Homo sapiens 14-18 9166850-7 1997 The in vitro kinase activities of CDK6 and CDK2 were prematurely increased by thiol deprivation. Sulfhydryl Compounds 78-83 cyclin dependent kinase 2 Homo sapiens 43-47 9139732-4 1997 Notably, two neighboring pRB phosphate acceptors, threonine 821 and threonine 826, which have previously been implicated in the regulation of LXCXE protein binding, are phosphorylated by different CDKs. Phosphates 29-38 cyclin dependent kinase 2 Homo sapiens 197-201 9188852-1 1997 Induction of the Myc-oestrogen receptor fusion protein (MycER) by 4-OH-tamoxifen (OHT) leads to the activation of Cyclin E/Cyclin-dependent kinase 2 (CycE/Cdk2) complexes followed by the induction of DNA synthesis. 4-oh-tamoxifen 66-80 cyclin dependent kinase 2 Homo sapiens 155-159 9139732-4 1997 Notably, two neighboring pRB phosphate acceptors, threonine 821 and threonine 826, which have previously been implicated in the regulation of LXCXE protein binding, are phosphorylated by different CDKs. Threonine 50-59 cyclin dependent kinase 2 Homo sapiens 197-201 9139732-4 1997 Notably, two neighboring pRB phosphate acceptors, threonine 821 and threonine 826, which have previously been implicated in the regulation of LXCXE protein binding, are phosphorylated by different CDKs. Threonine 68-77 cyclin dependent kinase 2 Homo sapiens 197-201 9139732-5 1997 We demonstrate that phosphorylation by either CDK2-cyclin A, which phosphorylates T821, or CDK4-cyclin D1, which phosphorylates threonine 826, can disable pRB for subsequent binding of an LXCXE protein. Threonine 128-137 cyclin dependent kinase 2 Homo sapiens 46-50 9099730-3 1997 We report herein that DL-threo-dihydrosphingosine (DHS), a competitive inhibitor of sphingosine kinase that prevents PDGF-induced SPP formation, specifically inhibited the activation of two cyclin-dependent kinases (p34(cdc2) kinase and Cdk2 kinase) induced by PDGF, but not by EGF. (2R,3R)-2-aminooctadecane-1,3-diol 22-49 cyclin dependent kinase 2 Homo sapiens 237-241 9099745-4 1997 Entry into S phase was preceded by increased activity of both Cdk4 and cyclin E-Cdk2 and hyperphosphorylation of pRB, all within the first 3-6 h of estradiol treatment. Estradiol 148-157 cyclin dependent kinase 2 Homo sapiens 80-84 9099745-9 1997 These apparently conflicting data were resolved by performing gel filtration chromatography, which revealed that only a minority of cyclin E-Cdk2 complexes were active following estradiol treatment. Estradiol 178-187 cyclin dependent kinase 2 Homo sapiens 141-145 9099730-3 1997 We report herein that DL-threo-dihydrosphingosine (DHS), a competitive inhibitor of sphingosine kinase that prevents PDGF-induced SPP formation, specifically inhibited the activation of two cyclin-dependent kinases (p34(cdc2) kinase and Cdk2 kinase) induced by PDGF, but not by EGF. dhs 51-54 cyclin dependent kinase 2 Homo sapiens 237-241 9099745-10 1997 Active complexes eluted at a higher molecular weight than inactive complexes, were relatively deficient in both p21 and p27, and contained Cdk2 with increased threonine 160 phosphorylation, consistent with a mechanism of activation of cyclin E-Cdk2 involving both reduced CDK inhibitor association and CDK-activating kinase-mediated phosphorylation of Cdk2. Threonine 159-168 cyclin dependent kinase 2 Homo sapiens 139-143 9099745-10 1997 Active complexes eluted at a higher molecular weight than inactive complexes, were relatively deficient in both p21 and p27, and contained Cdk2 with increased threonine 160 phosphorylation, consistent with a mechanism of activation of cyclin E-Cdk2 involving both reduced CDK inhibitor association and CDK-activating kinase-mediated phosphorylation of Cdk2. Threonine 159-168 cyclin dependent kinase 2 Homo sapiens 244-248 9099745-10 1997 Active complexes eluted at a higher molecular weight than inactive complexes, were relatively deficient in both p21 and p27, and contained Cdk2 with increased threonine 160 phosphorylation, consistent with a mechanism of activation of cyclin E-Cdk2 involving both reduced CDK inhibitor association and CDK-activating kinase-mediated phosphorylation of Cdk2. Threonine 159-168 cyclin dependent kinase 2 Homo sapiens 244-248 9103470-0 1997 Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. undecylprodigiosin 51-69 cyclin dependent kinase 2 Homo sapiens 116-141 9099745-11 1997 These results provide an explanation for the early activation of both cyclin D1-Cdk4 and cyclin E-Cdk2 complexes that accompany G1-S phase progression in response to estradiol. Estradiol 166-175 cyclin dependent kinase 2 Homo sapiens 98-102 9186612-0 1997 Eicosapentaenoic acid and docosahexaenoic acid inhibit DNA synthesis through inhibiting cdk2 kinase in vascular smooth muscle cells. Eicosapentaenoic Acid 0-21 cyclin dependent kinase 2 Homo sapiens 88-92 9186612-0 1997 Eicosapentaenoic acid and docosahexaenoic acid inhibit DNA synthesis through inhibiting cdk2 kinase in vascular smooth muscle cells. Docosahexaenoic Acids 26-46 cyclin dependent kinase 2 Homo sapiens 88-92 9141623-5 1997 Using Western blot analysis after subcellular fractionation, we revealed that after PDGF stimulation the phosphorylated (Thr 160), i.e., activated, form of cdk2 (33 kDa) first appeared in the nucleus at late G1-phase and persisted throughout until to the end of S-phase. Threonine 121-124 cyclin dependent kinase 2 Homo sapiens 156-160 9092548-8 1997 These results suggested that nitric oxide inhibits the G1/S transition by inhibiting Cdk2-mediated phosphorylation of the retinoblastoma protein and that p21 induction is involved in the Cdk2 inhibition. Nitric Oxide 29-41 cyclin dependent kinase 2 Homo sapiens 85-89 9092548-8 1997 These results suggested that nitric oxide inhibits the G1/S transition by inhibiting Cdk2-mediated phosphorylation of the retinoblastoma protein and that p21 induction is involved in the Cdk2 inhibition. Nitric Oxide 29-41 cyclin dependent kinase 2 Homo sapiens 187-191 9125124-0 1997 Butyrate stimulates cyclin D and p21 and inhibits cyclin-dependent kinase 2 expression in HT-29 colonic epithelial cells. Butyrates 0-8 cyclin dependent kinase 2 Homo sapiens 50-75 9093907-0 1997 Fas-induced changes in cdc2 and cdk2 kinase activity are not sufficient for triggering apoptosis in HUT-78 cells. ammonium ferrous sulfate 0-3 cyclin dependent kinase 2 Homo sapiens 32-36 9093907-3 1997 To investigate whether Fas-induced cell death activated cdc2 and cdk2 kinases inappropriately, the human T lymphoma cells HUT-78, which express a high copy number of Fas, and two other previously characterized subclones of the same cell line which express mutant, cell death-deficient dominant-negative forms of Fas, were Fas-challenged and the changes in cdc2 and cdk2 kinase activity monitored. ammonium ferrous sulfate 23-26 cyclin dependent kinase 2 Homo sapiens 65-69 9168006-6 1997 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. Estradiol 3-17 cyclin dependent kinase 2 Homo sapiens 128-153 9168006-6 1997 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. DDT 23-26 cyclin dependent kinase 2 Homo sapiens 128-153 9168007-4 1997 Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. Genistein 0-9 cyclin dependent kinase 2 Homo sapiens 82-107 9168007-4 1997 Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. Genistein 0-9 cyclin dependent kinase 2 Homo sapiens 109-113 9168007-4 1997 Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. Zearalenone 31-42 cyclin dependent kinase 2 Homo sapiens 82-107 9168007-4 1997 Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. Zearalenone 31-42 cyclin dependent kinase 2 Homo sapiens 109-113 21541623-3 1996 As a cytostatic mechanism, however, Flavopiridol strongly inhibits the cyclin-dependent kinases (cdk1, cdk2, cdk4, cdk7), with the potential to cause inhibition of cell cycle progression in G(1) and G(2) by multiple mechanisms relatable to cdk inhibition. alvocidib 36-48 cyclin dependent kinase 2 Homo sapiens 103-107 9049186-7 1997 The activity of cyclin-dependent kinase (Cdk)2 increased in growth-arrested T-47D and MCF-7 cells treated with beta-estradiol or DDT. Estradiol 111-125 cyclin dependent kinase 2 Homo sapiens 41-46 9049186-7 1997 The activity of cyclin-dependent kinase (Cdk)2 increased in growth-arrested T-47D and MCF-7 cells treated with beta-estradiol or DDT. DDT 129-132 cyclin dependent kinase 2 Homo sapiens 41-46 9049186-8 1997 The steroidal antiestrogen ICI 182,780 prevented both growth and Cdk2 activation induced by estradiol or DDT. Estradiol 92-101 cyclin dependent kinase 2 Homo sapiens 65-69 9049186-8 1997 The steroidal antiestrogen ICI 182,780 prevented both growth and Cdk2 activation induced by estradiol or DDT. DDT 105-108 cyclin dependent kinase 2 Homo sapiens 65-69 9049186-9 1997 Increased phosphorylation of Cdk2 and the retinoblastoma protein (pRb1O5) was observed in ER-positive cells treated with DDT or estradiol. DDT 121-124 cyclin dependent kinase 2 Homo sapiens 29-33 9049186-9 1997 Increased phosphorylation of Cdk2 and the retinoblastoma protein (pRb1O5) was observed in ER-positive cells treated with DDT or estradiol. Estradiol 128-137 cyclin dependent kinase 2 Homo sapiens 29-33 9030780-0 1997 Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. purine 42-48 cyclin dependent kinase 2 Homo sapiens 87-91 9030780-0 1997 Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Roscovitine 107-118 cyclin dependent kinase 2 Homo sapiens 87-91 9030780-7 1997 We determined the crystal structure of a complex between cdk2 and roscovitine at 0.24-nm (2.4 A) resolution and refined to an Rfactor of 0.18. Roscovitine 66-77 cyclin dependent kinase 2 Homo sapiens 57-61 9030780-8 1997 The purine portion of the inhibitor binds to the adenine binding pocket of cdk2. purine 4-10 cyclin dependent kinase 2 Homo sapiens 75-79 9030780-8 1997 The purine portion of the inhibitor binds to the adenine binding pocket of cdk2. Adenine 49-56 cyclin dependent kinase 2 Homo sapiens 75-79 9030780-10 1997 Analysis of the position of this benzyl ring explains the specificity of roscovitine in inhibiting cdk2. Roscovitine 73-84 cyclin dependent kinase 2 Homo sapiens 99-103 9030780-11 1997 The structure also reveals that the (R)-stereoisomer of roscovitine is bound to cdk2. Roscovitine 56-67 cyclin dependent kinase 2 Homo sapiens 80-84 9030780-13 1997 Results from structure/activity studies and from analysis of the cdk2/roscovitine complex crystal structure should allow the design of even more potent cdk inhibitors. Roscovitine 70-81 cyclin dependent kinase 2 Homo sapiens 65-69 9030781-0 1997 Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Roscovitine 36-47 cyclin dependent kinase 2 Homo sapiens 120-124 9030781-16 1997 Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities. Roscovitine 66-77 cyclin dependent kinase 2 Homo sapiens 205-209 9000124-0 1997 G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells. ginsenoside Rh2 54-69 cyclin dependent kinase 2 Homo sapiens 37-41 9063568-5 1997 The data showed that aloesin increased the levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells. aloesin 21-28 cyclin dependent kinase 2 Homo sapiens 63-67 9063568-7 1997 Collectively, these results suggest that aloesin stimulates the proliferation of SK-HEP-1 cells by inducing the intracellular levels of cyclin E/CDK2 kinase complex and CDC25A, which, together, result in the up-regulation of cyclin E-dependent kinase activity. aloesin 41-48 cyclin dependent kinase 2 Homo sapiens 145-149 9010227-5 1997 We provide evidence that this residue, serine 608 of pRB, is an authentic phosphorylation site that can be phosphorylated in vitro by cyclin A-CDK2 and cyclin D1-CDK4 kinases but not by cyclin E-CDK2 kinase or the mitogen activated kinase ERK2. Serine 39-45 cyclin dependent kinase 2 Homo sapiens 143-147 9010227-5 1997 We provide evidence that this residue, serine 608 of pRB, is an authentic phosphorylation site that can be phosphorylated in vitro by cyclin A-CDK2 and cyclin D1-CDK4 kinases but not by cyclin E-CDK2 kinase or the mitogen activated kinase ERK2. Serine 39-45 cyclin dependent kinase 2 Homo sapiens 195-199 9029153-3 1997 Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin-dependent kinases (Cdks). Serine 72-78 cyclin dependent kinase 2 Homo sapiens 148-152 8940249-5 1996 After release from mimosine treatment, 84% of the cell population remained in G1 up to 8 h. Treating breast cancer cells with 400 microM mimosine for 24 h inhibited cyclin E- and cyclin A-associated kinase activity by 85% or more, although immunoblots using anti-cyclin A, cyclin E, cdc2, and cdk2 antibodies showed that these key subunits were still present in the cells at pretreatment levels. Mimosine 137-145 cyclin dependent kinase 2 Homo sapiens 293-297 8917641-0 1996 High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design. Adenosine Triphosphate 87-90 cyclin dependent kinase 2 Homo sapiens 44-69 8917641-3 1996 The detailed structural analysis of CDK2 can provide valuable information for the design of new ligands that can bind in the ATP binding pocket and inhibit CDK2 activity. Adenosine Triphosphate 125-128 cyclin dependent kinase 2 Homo sapiens 36-40 8917641-3 1996 The detailed structural analysis of CDK2 can provide valuable information for the design of new ligands that can bind in the ATP binding pocket and inhibit CDK2 activity. Adenosine Triphosphate 125-128 cyclin dependent kinase 2 Homo sapiens 156-160 8917641-4 1996 For this objective, the crystal structures of human CDK2 apoenzyme and its ATP complex were refined to 1.8 and 1.9 A, respectively. Adenosine Triphosphate 75-78 cyclin dependent kinase 2 Homo sapiens 52-56 8917641-7 1996 Our analysis of CDK2 structural data, hydration of residues in the binding pocket of the apoenzyme, flexibility of the ligand, and structural differences between the apoenzyme and CDK2-ATP complex provide an explanation for the results of earlier binding studies with ATP analogues and a basis for future inhibitor design. Adenosine Triphosphate 185-188 cyclin dependent kinase 2 Homo sapiens 180-184 8917641-7 1996 Our analysis of CDK2 structural data, hydration of residues in the binding pocket of the apoenzyme, flexibility of the ligand, and structural differences between the apoenzyme and CDK2-ATP complex provide an explanation for the results of earlier binding studies with ATP analogues and a basis for future inhibitor design. Adenosine Triphosphate 268-271 cyclin dependent kinase 2 Homo sapiens 180-184 8810266-4 1996 To gain further insights into these mechanisms, we explored the effects of O2 exposure on G1 cyclins and their cyclin-dependent kinases (CDKs). Oxygen 75-77 cyclin dependent kinase 2 Homo sapiens 137-141 9089005-11 1996 In IL-2-stimulated cells, the levels of Cdk2 were found to be lower in PG-treated cells than those detected in controls. Prostaglandins 71-73 cyclin dependent kinase 2 Homo sapiens 40-44 8900110-3 1996 Ara-C treatment of cells that express wild type or a dominant negative, kinase-inactive c-Abl(K-R) was associated with formation of c-Abl-p53 complexes and increased expression of the cyclin-dependent kinase (Cdk) inhibitor p21. Cytarabine 0-5 cyclin dependent kinase 2 Homo sapiens 209-212 8900110-3 1996 Ara-C treatment of cells that express wild type or a dominant negative, kinase-inactive c-Abl(K-R) was associated with formation of c-Abl-p53 complexes and increased expression of the cyclin-dependent kinase (Cdk) inhibitor p21. Krypton 94-97 cyclin dependent kinase 2 Homo sapiens 209-212 8900110-4 1996 However, down-regulation of Cdk2 by ara-C was found in cells expressing wild type c-Abl and not in cells expressing c-Abl(K-R) or those deficient in p53. Cytarabine 36-41 cyclin dependent kinase 2 Homo sapiens 28-32 8806683-4 1996 The results also demonstrate that Cdk2 directly associates with the Src-like tyrosine kinase Lyn as a consequence of ara-C-treatment. Cytarabine 117-122 cyclin dependent kinase 2 Homo sapiens 34-38 8891334-1 1996 The addition of 10 nM staurosporine (ST) to MDA 361 breast carcinoma cells induces a G1 arrest, which correlates with the loss of the catalytic activity of the G1-associated cyclin-dependent kinases (cdks) and increased levels of underphosphorylated retinoblastoma protein. Staurosporine 22-35 cyclin dependent kinase 2 Homo sapiens 200-204 8891334-1 1996 The addition of 10 nM staurosporine (ST) to MDA 361 breast carcinoma cells induces a G1 arrest, which correlates with the loss of the catalytic activity of the G1-associated cyclin-dependent kinases (cdks) and increased levels of underphosphorylated retinoblastoma protein. Staurosporine 37-39 cyclin dependent kinase 2 Homo sapiens 200-204 8891334-6 1996 The reduction in the level of the active phosphorylated form of cdk2 also correlated with an increase in the level of p27Kip, which has been shown to inhibit the phosphorylation of the activating Thr-160 residue of cdk2. Threonine 196-199 cyclin dependent kinase 2 Homo sapiens 64-68 8891334-6 1996 The reduction in the level of the active phosphorylated form of cdk2 also correlated with an increase in the level of p27Kip, which has been shown to inhibit the phosphorylation of the activating Thr-160 residue of cdk2. Threonine 196-199 cyclin dependent kinase 2 Homo sapiens 215-219 8836101-1 1996 Cyclin-dependent kinases (CDKs), which play a key role in cell cycle control, are activated by the CDK activating kinase (CAK), which activates cyclin-bound CDKs by phosphorylation at a specific threonine residue. Threonine 195-204 cyclin dependent kinase 2 Homo sapiens 26-30 8836101-1 1996 Cyclin-dependent kinases (CDKs), which play a key role in cell cycle control, are activated by the CDK activating kinase (CAK), which activates cyclin-bound CDKs by phosphorylation at a specific threonine residue. Threonine 195-204 cyclin dependent kinase 2 Homo sapiens 157-161 8806683-0 1996 Interaction of cyclin-dependent kinase 2 and the Lyn tyrosine kinase in cells treated with 1-beta-D-arabinofuranosylcytosine. Cytarabine 91-124 cyclin dependent kinase 2 Homo sapiens 15-40 8806683-8 1996 These findings suggest that the association of Lyn and Cdk2 in ara-C-treated cells may contribute to regulation of Cdk2-dependent cell cycle checkpoints. Cytarabine 63-68 cyclin dependent kinase 2 Homo sapiens 55-59 8806683-3 1996 The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. Cytarabine 67-100 cyclin dependent kinase 2 Homo sapiens 156-160 8806683-3 1996 The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. Cytarabine 67-100 cyclin dependent kinase 2 Homo sapiens 179-183 8806683-8 1996 These findings suggest that the association of Lyn and Cdk2 in ara-C-treated cells may contribute to regulation of Cdk2-dependent cell cycle checkpoints. Cytarabine 63-68 cyclin dependent kinase 2 Homo sapiens 115-119 8806683-3 1996 The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. Cytarabine 102-107 cyclin dependent kinase 2 Homo sapiens 156-160 8797888-5 1996 MKN-28 was an exception; it contained mutated p53, and expressed mRNAs for p21, CDK2 and G1 cyclins at high levels. mkn-28 0-6 cyclin dependent kinase 2 Homo sapiens 80-84 8806683-3 1996 The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. Cytarabine 102-107 cyclin dependent kinase 2 Homo sapiens 179-183 8806683-3 1996 The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. Tyrosine 128-136 cyclin dependent kinase 2 Homo sapiens 156-160 8885238-7 1996 Rapamycin, an immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2 activation, blocked telomerase induction. Sirolimus 0-9 cyclin dependent kinase 2 Homo sapiens 85-89 8684460-4 1996 On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP. Adenosine Triphosphate 110-113 cyclin dependent kinase 2 Homo sapiens 3-7 8756328-3 1996 The phosphate group, which is on the regulatory T-loop of CDK2, is mostly buried, its charge being neutralized by three Arg side chains. Phosphates 4-13 cyclin dependent kinase 2 Homo sapiens 58-62 8756328-3 1996 The phosphate group, which is on the regulatory T-loop of CDK2, is mostly buried, its charge being neutralized by three Arg side chains. Arginine 120-123 cyclin dependent kinase 2 Homo sapiens 58-62 8756328-4 1996 The arginines help extend the influence of the phosphate group through a network of hydrogen bonds to both CDK2 and cyclinA. Arginine 4-13 cyclin dependent kinase 2 Homo sapiens 107-111 8756328-4 1996 The arginines help extend the influence of the phosphate group through a network of hydrogen bonds to both CDK2 and cyclinA. Phosphates 47-56 cyclin dependent kinase 2 Homo sapiens 107-111 8756328-4 1996 The arginines help extend the influence of the phosphate group through a network of hydrogen bonds to both CDK2 and cyclinA. Hydrogen 84-92 cyclin dependent kinase 2 Homo sapiens 107-111 8756328-6 1996 The phosphate group thus acts as a major organizing centre in the CDK2-CyclinA complex. Phosphates 4-13 cyclin dependent kinase 2 Homo sapiens 66-70 8674031-0 1996 Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 50-81 8668211-4 1996 The latter resulted from the rapid alpha-interferon-mediated elimination of cdc25A, a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk2 in cyclin-cdk complexes. Tyrosine 142-150 cyclin dependent kinase 2 Homo sapiens 170-174 8674031-8 1996 Flavopiridol inhibited the in vitro kinase activity of CDK2 using an immune complex kinase assay (IC50, 100 nM at 400 microM ATP). alvocidib 0-12 cyclin dependent kinase 2 Homo sapiens 55-59 8674031-8 1996 Flavopiridol inhibited the in vitro kinase activity of CDK2 using an immune complex kinase assay (IC50, 100 nM at 400 microM ATP). Adenosine Triphosphate 125-128 cyclin dependent kinase 2 Homo sapiens 55-59 8674031-9 1996 Immunoprecipitated CDK2 kinase activity from either MCF-7 or MDA-MB-468 cells exposed to Flavopiridol (300 nM) for increasing time showed an initial increased activity (approximately 1.5-fold at 3 h) compared with untreated cells, followed by a loss of kinase activity to immeasurable levels by 24 h. This increased immunoprecipitated kinase activity was dependent on the Flavopiridol concentration added to intact cells and was associated with a reduction of CDK2 tyrosine phosphorylation. alvocidib 89-101 cyclin dependent kinase 2 Homo sapiens 19-23 8674031-9 1996 Immunoprecipitated CDK2 kinase activity from either MCF-7 or MDA-MB-468 cells exposed to Flavopiridol (300 nM) for increasing time showed an initial increased activity (approximately 1.5-fold at 3 h) compared with untreated cells, followed by a loss of kinase activity to immeasurable levels by 24 h. This increased immunoprecipitated kinase activity was dependent on the Flavopiridol concentration added to intact cells and was associated with a reduction of CDK2 tyrosine phosphorylation. alvocidib 89-101 cyclin dependent kinase 2 Homo sapiens 460-464 8674031-9 1996 Immunoprecipitated CDK2 kinase activity from either MCF-7 or MDA-MB-468 cells exposed to Flavopiridol (300 nM) for increasing time showed an initial increased activity (approximately 1.5-fold at 3 h) compared with untreated cells, followed by a loss of kinase activity to immeasurable levels by 24 h. This increased immunoprecipitated kinase activity was dependent on the Flavopiridol concentration added to intact cells and was associated with a reduction of CDK2 tyrosine phosphorylation. alvocidib 372-384 cyclin dependent kinase 2 Homo sapiens 19-23 8674031-9 1996 Immunoprecipitated CDK2 kinase activity from either MCF-7 or MDA-MB-468 cells exposed to Flavopiridol (300 nM) for increasing time showed an initial increased activity (approximately 1.5-fold at 3 h) compared with untreated cells, followed by a loss of kinase activity to immeasurable levels by 24 h. This increased immunoprecipitated kinase activity was dependent on the Flavopiridol concentration added to intact cells and was associated with a reduction of CDK2 tyrosine phosphorylation. Tyrosine 465-473 cyclin dependent kinase 2 Homo sapiens 19-23 8674031-11 1996 Inhibition of the CDK4 and/or CDK2 kinase activity by Flavopiridol can therefore account for the G1 arrest observed after exposure to Flavopiridol. alvocidib 54-66 cyclin dependent kinase 2 Homo sapiens 30-34 8674031-11 1996 Inhibition of the CDK4 and/or CDK2 kinase activity by Flavopiridol can therefore account for the G1 arrest observed after exposure to Flavopiridol. alvocidib 134-146 cyclin dependent kinase 2 Homo sapiens 30-34 8626531-5 1996 PMA inhibited the histone H1 kinase activity of Cdk2, which increased from about 9 h, whereas PMA did not inhibit the pRb kinase activities of cyclin D-associated kinase(s) and Cdk4, detectable from 0-3 h. These results suggested that the PMA-induced inhibition of pRb phosphorylation is not mediated by suppressing cyclin D-associated kinase(s) including Cdk4, but involves the suppression of Cdk2 activity that results from the reduced expression of cyclins E and A. Tetradecanoylphorbol Acetate 0-3 cyclin dependent kinase 2 Homo sapiens 48-52 8650198-10 1996 In pRB+ cells, p2l was preferentially associated with Thrl6O phosphorylated active CDK2. thrl6o 54-60 cyclin dependent kinase 2 Homo sapiens 83-87 8662825-8 1996 Taken together, these results suggest that different CDKs are inhibited by different mechanisms following UV-induced DNA damage: Cdk2 is inhibited by the elevated level of p21; Cdk4 is inhibited by cooperation of p21 with other CDK inhibitors, like p27, and possibly by phosphorylation; and Cdc2 is inhibited by Thr-14/Tyr-15 phosphorylation. Threonine 312-315 cyclin dependent kinase 2 Homo sapiens 129-133 8662825-8 1996 Taken together, these results suggest that different CDKs are inhibited by different mechanisms following UV-induced DNA damage: Cdk2 is inhibited by the elevated level of p21; Cdk4 is inhibited by cooperation of p21 with other CDK inhibitors, like p27, and possibly by phosphorylation; and Cdc2 is inhibited by Thr-14/Tyr-15 phosphorylation. Tyrosine 319-322 cyclin dependent kinase 2 Homo sapiens 129-133 8732680-3 1996 Treatment of growth-arrested MCF-7 cells with physiological concentrations of estradiol led to a time-dependent increase in Cdk2-associated and cyclin E-dependent kinase activity, which was accompanied by hyperphosphorylation of Rb and S-phase entry. Estradiol 78-87 cyclin dependent kinase 2 Homo sapiens 124-128 8732680-4 1996 Induction of both Cdk2 activity and DNA synthesis by estradiol was dose dependent and was inhibited by coadministration of ICI 182,780. Estradiol 53-62 cyclin dependent kinase 2 Homo sapiens 18-22 8732680-5 1996 Elicitation of Cdk2 activity was found to require prolonged (> 8h) estradiol exposure. Estradiol 70-79 cyclin dependent kinase 2 Homo sapiens 15-19 8732680-8 1996 Cdk2 and Cdk4 protein levels were not altered by estrogen treatment; however, faster migrating, phosphorylated Cdk2 forms increased in estradiol-treated MCF-7 cells by 12 after release from growth arrest. Estradiol 135-144 cyclin dependent kinase 2 Homo sapiens 0-4 8732680-8 1996 Cdk2 and Cdk4 protein levels were not altered by estrogen treatment; however, faster migrating, phosphorylated Cdk2 forms increased in estradiol-treated MCF-7 cells by 12 after release from growth arrest. Estradiol 135-144 cyclin dependent kinase 2 Homo sapiens 111-115 8626584-3 1996 Dominant negative mutants of CDC2, CDK2, and CDK3 each suppressed apoptosis induced by both staurosporine and tumor necrosis factor alpha, whereas a dominant negative mutant of CDK5 was without effect. Staurosporine 92-105 cyclin dependent kinase 2 Homo sapiens 35-39 8650198-0 1996 G1 arrest and down-regulation of cyclin E/cyclin-dependent kinase 2 by the protein kinase inhibitor staurosporine are dependent on the retinoblastoma protein in the bladder carcinoma cell line 5637. Staurosporine 100-113 cyclin dependent kinase 2 Homo sapiens 42-67 8650198-9 1996 Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. Staurosporine 52-65 cyclin dependent kinase 2 Homo sapiens 23-27 8650198-9 1996 Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. Staurosporine 52-65 cyclin dependent kinase 2 Homo sapiens 140-144 8650198-9 1996 Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. Staurosporine 159-172 cyclin dependent kinase 2 Homo sapiens 23-27 8635520-6 1996 The expression of cdk2 and cyclin D1 in the quiescent cells was reduced after stimulation by renewal of the medium and then increased, accompanied by Rb phosphorylation and cdc2 expression around the G1/S transition. Rubidium 150-152 cyclin dependent kinase 2 Homo sapiens 18-22 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Cysteine 13-16 cyclin dependent kinase 2 Homo sapiens 57-61 8601310-3 1996 CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. Histidine 101-104 cyclin dependent kinase 2 Homo sapiens 0-4 8601310-3 1996 CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. Glutamic Acid 112-115 cyclin dependent kinase 2 Homo sapiens 0-4 8601310-5 1996 One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle. Phosphates 55-64 cyclin dependent kinase 2 Homo sapiens 115-119 8601310-5 1996 One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle. Phosphates 55-64 cyclin dependent kinase 2 Homo sapiens 152-156 8601310-5 1996 One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle. Adenosine Triphosphate 95-98 cyclin dependent kinase 2 Homo sapiens 115-119 8601310-5 1996 One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle. Adenosine Triphosphate 95-98 cyclin dependent kinase 2 Homo sapiens 152-156 8610110-0 1996 Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Flavonoids 50-59 cyclin dependent kinase 2 Homo sapiens 79-83 8610110-6 1996 The aromatic portion of the inhibitor binds to the adenine-binding pocket of CDK2, and the position of the phenyl group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP complex structure. Adenine 51-58 cyclin dependent kinase 2 Homo sapiens 77-81 8610110-6 1996 The aromatic portion of the inhibitor binds to the adenine-binding pocket of CDK2, and the position of the phenyl group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP complex structure. Adenosine Triphosphate 212-215 cyclin dependent kinase 2 Homo sapiens 77-81 8610110-7 1996 The analysis of the position of this phenyl ring not only explains the great differences of kinase inhibition among the flavonoid inhibitors but also explains the specificity of L868276 to inhibit CDK2 and CDC2. L 868276 178-185 cyclin dependent kinase 2 Homo sapiens 197-201 8838866-8 1996 Although increased activities and/or expression of cyclin A and cdk2 and cdk4 proteins, but not ERK1 or ERK2, were associated with immortalization, similar increases were found in staurosporine-sensitive precrisis cells expressing SV40 tumor antigens. Staurosporine 180-193 cyclin dependent kinase 2 Homo sapiens 64-68 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Cysteine 13-16 cyclin dependent kinase 2 Homo sapiens 91-95 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Cysteine 13-16 cyclin dependent kinase 2 Homo sapiens 91-95 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Serine 24-27 cyclin dependent kinase 2 Homo sapiens 57-61 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Serine 24-27 cyclin dependent kinase 2 Homo sapiens 91-95 8617791-6 1996 While Cdc25A Cys --> Ser could interact with cyclin A-Cdk2, cyclin B-Cdc2, and cyclin E-Cdk2 strongly, Cdc25B mutant was only found to bind to cyclin A-Cdk2 at significant levels. Serine 24-27 cyclin dependent kinase 2 Homo sapiens 91-95 8549662-7 1996 Parallel to their effect on cell cycle, ASA and indomethacin also reduced the levels of p34cdc2 and p33cdk2, two cyclin-dependent kinases that are important for cell cycle progression. Aspirin 40-43 cyclin dependent kinase 2 Homo sapiens 100-107 8822203-3 1996 We now show that bromodeoxyuridine (BrdUrd), a thymidine analogue and radiation sensitizer, inhibits growth and activity of cyclin A-cdk2 kinase in metastatic C8161 and nonmetastatic neo 6.3/C8161 human melanoma cells. Bromodeoxyuridine 17-34 cyclin dependent kinase 2 Homo sapiens 133-137 9244189-3 1996 In this cell type addition of phorbol-12, 13-dibutyrate 5 h but not 16 h after serum stimulation completely inhibits CDK2 kinase activation and DNA synthesis. Phorbol 12,13-Dibutyrate 30-55 cyclin dependent kinase 2 Homo sapiens 117-121 8622677-4 1996 The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. prostaglandin A2 146-150 cyclin dependent kinase 2 Homo sapiens 97-101 8622677-5 1996 Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. prostaglandin A2 84-88 cyclin dependent kinase 2 Homo sapiens 76-80 8622677-6 1996 Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. prostaglandin A2 107-111 cyclin dependent kinase 2 Homo sapiens 229-233 8622677-6 1996 Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. prostaglandin A2 319-323 cyclin dependent kinase 2 Homo sapiens 229-233 8622677-7 1996 Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. prostaglandin A2 169-173 cyclin dependent kinase 2 Homo sapiens 70-74 8645257-3 1996 UCN-01 inhibited the retinoblastoma susceptibility gene product (pRB) kinase activity of three types of cdks (cdk 2, 4 and 6) with 50% inhibitory concentration values of 42, 32, and 58 nM, respectively, in vitro. 7-hydroxystaurosporine 0-6 cyclin dependent kinase 2 Homo sapiens 104-108 8645257-3 1996 UCN-01 inhibited the retinoblastoma susceptibility gene product (pRB) kinase activity of three types of cdks (cdk 2, 4 and 6) with 50% inhibitory concentration values of 42, 32, and 58 nM, respectively, in vitro. 7-hydroxystaurosporine 0-6 cyclin dependent kinase 2 Homo sapiens 110-124 8564956-1 1996 Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity. prostaglandin A2 0-16 cyclin dependent kinase 2 Homo sapiens 232-257 8564956-1 1996 Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity. prostaglandin A2 18-22 cyclin dependent kinase 2 Homo sapiens 232-257 8549662-7 1996 Parallel to their effect on cell cycle, ASA and indomethacin also reduced the levels of p34cdc2 and p33cdk2, two cyclin-dependent kinases that are important for cell cycle progression. Indomethacin 48-60 cyclin dependent kinase 2 Homo sapiens 100-107 8594303-6 1996 A second, later effect of rapamycin in IL-2-stimulated T cells is an inhibition of the enzymatic activity of the cyclin-dependent kinase cdk2-cyclin E complex, which functions as a crucial regulator of G1/S transition. Sirolimus 26-35 cyclin dependent kinase 2 Homo sapiens 137-141 8788034-6 1996 RA-induced reduction in Cdk2 activity was modest and occurred after %S phase declined, while Cdk4 activity was reduced, coincident with cell cycle changes. Tretinoin 0-2 cyclin dependent kinase 2 Homo sapiens 24-28 7589260-13 1995 These results demonstrate that TPA blocks the G1/S transition in Demel melanoma cells in late G1 by mechanisms which regulate phosphorylation and activation of the CDK2 kinase. Tetradecanoylphorbol Acetate 31-34 cyclin dependent kinase 2 Homo sapiens 164-168 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. Serine 92-95 cyclin dependent kinase 2 Homo sapiens 0-25 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. Serine 92-95 cyclin dependent kinase 2 Homo sapiens 27-31 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. Threonine 96-99 cyclin dependent kinase 2 Homo sapiens 0-25 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. Threonine 96-99 cyclin dependent kinase 2 Homo sapiens 27-31 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. pro-x-basic amino acid 100-122 cyclin dependent kinase 2 Homo sapiens 0-25 7488142-1 1995 Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. pro-x-basic amino acid 100-122 cyclin dependent kinase 2 Homo sapiens 27-31 7488142-3 1995 Peptides containing a proline residue in the sequence Pro-X-Thr-Pro-X-basic amino acid (motif B) had higher affinity for both Cdk2 complexes than peptides containing motif A. Proline 22-29 cyclin dependent kinase 2 Homo sapiens 126-130 7488142-3 1995 Peptides containing a proline residue in the sequence Pro-X-Thr-Pro-X-basic amino acid (motif B) had higher affinity for both Cdk2 complexes than peptides containing motif A. pro-x-thr-pro-x-basic amino acid 54-86 cyclin dependent kinase 2 Homo sapiens 126-130 7488142-4 1995 Furthermore, differences in substrate affinity between the two Cdk2 complexes were caused by a proline residue adjacent to or three positions before the threonine residue. Proline 95-102 cyclin dependent kinase 2 Homo sapiens 63-67 7488142-4 1995 Furthermore, differences in substrate affinity between the two Cdk2 complexes were caused by a proline residue adjacent to or three positions before the threonine residue. Threonine 153-162 cyclin dependent kinase 2 Homo sapiens 63-67 9552391-3 1996 In this article five structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine complex, isopentenyladenine complex, and des-chloro-flavopiridol complex. Adenosine Triphosphate 74-77 cyclin dependent kinase 2 Homo sapiens 41-45 9552391-3 1996 In this article five structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine complex, isopentenyladenine complex, and des-chloro-flavopiridol complex. olomoucine 87-97 cyclin dependent kinase 2 Homo sapiens 41-45 9552391-3 1996 In this article five structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine complex, isopentenyladenine complex, and des-chloro-flavopiridol complex. N(6)-(delta(2)-isopentenyl)adenine 107-125 cyclin dependent kinase 2 Homo sapiens 41-45 9552391-3 1996 In this article five structures of human CDK2 are summarised: apoprotein, ATP complex, olomoucine complex, isopentenyladenine complex, and des-chloro-flavopiridol complex. deschloroflavopiridol 139-162 cyclin dependent kinase 2 Homo sapiens 41-45 7589260-0 1995 Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity. Tetradecanoylphorbol Acetate 79-115 cyclin dependent kinase 2 Homo sapiens 139-143 7589260-0 1995 Inhibition of the melanoma cell cycle and regulation at the G1/S transition by 12-O-tetradecanoylphorbol-13-acetate (TPA) by modulation of CDK2 activity. Tetradecanoylphorbol Acetate 117-120 cyclin dependent kinase 2 Homo sapiens 139-143 7589260-3 1995 To investigate the mechanism by which TPA arrests melanoma cell growth at the G1/S transition we have examined its effects on the levels of cyclins and cyclin dependent kinases (CDKs) and activation of CDK2 kinase activity. Tetradecanoylphorbol Acetate 38-41 cyclin dependent kinase 2 Homo sapiens 202-206 7589260-5 1995 When TPA was added in G1, it inhibited the mobility shift of CDK2 reflecting a change in phosphorylation state. Tetradecanoylphorbol Acetate 5-8 cyclin dependent kinase 2 Homo sapiens 61-65 7593219-12 1995 Cells arrested by nocodazole had high levels of active p34cdc2 and greatly reduced levels of p33cdk2 kinase activity. Nocodazole 18-28 cyclin dependent kinase 2 Homo sapiens 93-100 7569954-1 1995 The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Threonine 94-103 cyclin dependent kinase 2 Homo sapiens 44-48 7569954-1 1995 The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Threonine 94-103 cyclin dependent kinase 2 Homo sapiens 115-119 7574801-4 1995 Butyrolactone I inhibits both cdc2 and CDK2 kinase in the cell-free system. butyrolactone I 0-15 cyclin dependent kinase 2 Homo sapiens 39-43 7574801-7 1995 UCN-01, a protein kinase-C inhibitor, also inhibits both cdc2 and CDK2 kinase. 7-hydroxystaurosporine 0-6 cyclin dependent kinase 2 Homo sapiens 66-70 7624134-0 1995 Cdk2 kinase phosphorylates serine 315 of human p53 in vitro. Serine 27-33 cyclin dependent kinase 2 Homo sapiens 0-4 7641182-0 1995 Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1 correlates with the dephosphorylation of cyclin-dependent kinase 2. bryostatin 1 69-81 cyclin dependent kinase 2 Homo sapiens 123-148 7641182-2 1995 Both bryostatin 1 and PMA induced inhibition of cyclin-dependent kinase 2 (cdk2) activity. bryostatin 1 5-17 cyclin dependent kinase 2 Homo sapiens 48-73 7641182-2 1995 Both bryostatin 1 and PMA induced inhibition of cyclin-dependent kinase 2 (cdk2) activity. bryostatin 1 5-17 cyclin dependent kinase 2 Homo sapiens 75-79 7641182-2 1995 Both bryostatin 1 and PMA induced inhibition of cyclin-dependent kinase 2 (cdk2) activity. Tetradecanoylphorbol Acetate 22-25 cyclin dependent kinase 2 Homo sapiens 48-73 7641182-2 1995 Both bryostatin 1 and PMA induced inhibition of cyclin-dependent kinase 2 (cdk2) activity. Tetradecanoylphorbol Acetate 22-25 cyclin dependent kinase 2 Homo sapiens 75-79 7641182-4 1995 In contrast, the second phase of cdk2 inhibition correlated with the dephosphorylation of cdk2 on threonine-160, which must be phosphorylated for cdk2 activity. Threonine 98-107 cyclin dependent kinase 2 Homo sapiens 33-37 7641182-4 1995 In contrast, the second phase of cdk2 inhibition correlated with the dephosphorylation of cdk2 on threonine-160, which must be phosphorylated for cdk2 activity. Threonine 98-107 cyclin dependent kinase 2 Homo sapiens 90-94 7641182-4 1995 In contrast, the second phase of cdk2 inhibition correlated with the dephosphorylation of cdk2 on threonine-160, which must be phosphorylated for cdk2 activity. Threonine 98-107 cyclin dependent kinase 2 Homo sapiens 90-94 7641182-5 1995 The level of growth inhibition induced by these two compounds correlated with the degree of cdk2 dephosphorylation as follows: bryostatin 1, 60%; PMA, 100%. bryostatin 1 127-139 cyclin dependent kinase 2 Homo sapiens 92-96 7641182-5 1995 The level of growth inhibition induced by these two compounds correlated with the degree of cdk2 dephosphorylation as follows: bryostatin 1, 60%; PMA, 100%. Tetradecanoylphorbol Acetate 146-149 cyclin dependent kinase 2 Homo sapiens 92-96 7479711-4 1995 We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6-(delta 2-isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. N(6)-(delta(2)-isopentenyl)adenine 98-129 cyclin dependent kinase 2 Homo sapiens 55-59 7479711-4 1995 We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6-(delta 2-isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. olomoucine 166-176 cyclin dependent kinase 2 Homo sapiens 55-59 7479711-5 1995 Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. Adenine 20-27 cyclin dependent kinase 2 Homo sapiens 82-86 7479711-5 1995 Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. Adenine 56-63 cyclin dependent kinase 2 Homo sapiens 82-86 7479711-5 1995 Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. Adenine 56-63 cyclin dependent kinase 2 Homo sapiens 82-86 7479711-5 1995 Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. Adenosine Triphosphate 176-179 cyclin dependent kinase 2 Homo sapiens 82-86 7479711-7 1995 The structural information from the CDK2-olomoucine complex will be useful in directing the search for the next generation inhibitors with improved properties. olomoucine 41-51 cyclin dependent kinase 2 Homo sapiens 36-40 7630397-1 1995 The crystal structure of the human cyclinA-cyclin-dependent kinase2 (CDK2)-ATP complex has been determined at 2.3 A resolution. Adenosine Triphosphate 75-78 cyclin dependent kinase 2 Homo sapiens 35-67 7630397-1 1995 The crystal structure of the human cyclinA-cyclin-dependent kinase2 (CDK2)-ATP complex has been determined at 2.3 A resolution. Adenosine Triphosphate 75-78 cyclin dependent kinase 2 Homo sapiens 69-73 7662974-0 1995 Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase. Iron 11-15 cyclin dependent kinase 2 Homo sapiens 166-173 7662974-10 1995 A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. Deferoxamine 18-21 cyclin dependent kinase 2 Homo sapiens 167-174 7662974-11 1995 The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle. Deferoxamine 89-92 cyclin dependent kinase 2 Homo sapiens 35-42 7624134-8 1995 Mutation of serine 315 of p53 to alanine (p53-S315A) abolished phosphorylation by cdk2 kinase. Serine 12-18 cyclin dependent kinase 2 Homo sapiens 82-86 7624134-8 1995 Mutation of serine 315 of p53 to alanine (p53-S315A) abolished phosphorylation by cdk2 kinase. Alanine 33-40 cyclin dependent kinase 2 Homo sapiens 82-86 7624134-10 1995 The results demonstrate that ser 315 of p53 is phosphorylated by cdk2 in vitro. Serine 29-32 cyclin dependent kinase 2 Homo sapiens 65-69 7784076-2 1995 To investigate the molecular basis of the interaction between these proteins and the cyclin-dependent kinases (CDKs), we performed a systematic mutagenesis of the CKI family member p21Cip1 using the alanine-scanning strategy. Alanine 199-206 cyclin dependent kinase 2 Homo sapiens 111-115 7954429-0 1994 The kinase inhibitor staurosporine induces G1 arrest at two points: effect on retinoblastoma protein phosphorylation and cyclin-dependent kinase 2 in normal and transformed cells. Staurosporine 21-34 cyclin dependent kinase 2 Homo sapiens 121-146 7611786-6 1995 It is likely that gene alteration of sdil and subsequent loss of function may have implication for cdk2 and G1 cyclins expression. sdil 37-41 cyclin dependent kinase 2 Homo sapiens 99-103 7806527-8 1994 These data demonstrate that 1) the signals that lead to induction of competence in T cells stimulate an IL-2-independent and CsA-resistant phase of Cdk4 and cyclin D2 expression, Cdk4 kinase activity, and Cdk2 kinase activity, and 2) IL-2 stimulates a second phase of Cdk4 and cyclin D2 expression and de novo expression of Cdk2 in these cells. Cyclosporine 125-128 cyclin dependent kinase 2 Homo sapiens 205-209 7806527-8 1994 These data demonstrate that 1) the signals that lead to induction of competence in T cells stimulate an IL-2-independent and CsA-resistant phase of Cdk4 and cyclin D2 expression, Cdk4 kinase activity, and Cdk2 kinase activity, and 2) IL-2 stimulates a second phase of Cdk4 and cyclin D2 expression and de novo expression of Cdk2 in these cells. Cyclosporine 125-128 cyclin dependent kinase 2 Homo sapiens 324-328 7881438-0 1994 Dinucleotide repeat polymorphism adjacent to CDKN2. Dinucleoside Phosphates 0-12 cyclin dependent kinase 2 Homo sapiens 45-50 7752470-2 1995 Binding of Cdks to cyclins and threonine phosphorylation in the Cdks are required to form fully active holo-Cdks. Threonine 31-40 cyclin dependent kinase 2 Homo sapiens 11-15 7752470-2 1995 Binding of Cdks to cyclins and threonine phosphorylation in the Cdks are required to form fully active holo-Cdks. Threonine 31-40 cyclin dependent kinase 2 Homo sapiens 64-68 7752470-2 1995 Binding of Cdks to cyclins and threonine phosphorylation in the Cdks are required to form fully active holo-Cdks. Threonine 31-40 cyclin dependent kinase 2 Homo sapiens 64-68 7935441-3 1994 This step is catalyzed by a cdk-activating kinase (CAK) functionally analogous to the enzyme which phosphorylates cdc2 and cdk2 at Thr-161/160. Threonine 131-134 cyclin dependent kinase 2 Homo sapiens 123-127 7945302-3 1994 Nuclear cdk2 forms high molecular weight complexes which migrate at the same position as DNA polymerase alpha and proliferating cell nuclear antigen in sucrose gradient centrifugation experiments. Sucrose 152-159 cyclin dependent kinase 2 Homo sapiens 8-12 7848906-0 1994 Release from G0/G1 arrest induced by dimethyl sulfoxide in human lymphoid cells: regulation of synthesis and activation of the p33cdk2 and p34cdc2 kinases. Dimethyl Sulfoxide 37-55 cyclin dependent kinase 2 Homo sapiens 127-134 8033212-3 1994 p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, cyclin A-Cdk2, and cyclin D2-Cdk4. Rubidium 26-28 cyclin dependent kinase 2 Homo sapiens 57-61 8058318-4 1994 Butyrolactone I inhibited phosphorylation of pRB catalyzed by cyclin A-cdk2 produced by baculovirus in vitro. butyrolactone I 0-15 cyclin dependent kinase 2 Homo sapiens 71-75 8033212-3 1994 p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, cyclin A-Cdk2, and cyclin D2-Cdk4. Rubidium 26-28 cyclin dependent kinase 2 Homo sapiens 72-76 17180006-6 1994 In this study we isolated RA-resistant 15N cell lines and analyzed their growth properties and changes in cell cycle related (cdc2, cdk2, cyclins A, B, D and E) and early response (fos and jun) gene expression to evaluate the role IGF2 may play in mediating RA resistance. Tretinoin 26-28 cyclin dependent kinase 2 Homo sapiens 132-136 8012959-6 1994 AGM-1470 inhibits growth factor-induced activation of candidate RB kinases cdc2 and cdk2 but fails to inhibit them directly in vitro. O-(Chloroacetylcarbamoyl)fumagillol 0-8 cyclin dependent kinase 2 Homo sapiens 84-88 10465025-8 1994 These findings indicate that vitamin D3 analogues regulate cell proliferation by control of the transition of G1 and G2+M phases, reminiscent of the cdc2/CDK2 type of cell cycle control. Cholecalciferol 29-39 cyclin dependent kinase 2 Homo sapiens 154-158 8108147-0 1994 Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E. Cyclin E is a cell cycle-regulated protein that activates the cdc2-related protein kinases cdk2 shortly before S-phase entry. Tetracycline 49-61 cyclin dependent kinase 2 Homo sapiens 193-197 8168106-5 1994 The nickel-transformed HOS clones expressed the major regulators of Rb phosphorylation, cyclin E and cdk-2, at levels similar to those of the parental cells. Nickel 4-10 cyclin dependent kinase 2 Homo sapiens 101-106 8175758-9 1994 cdc2 and cdk2 bind to p9CKShs1-Sepharose, but not to p15cdk-BP. Sepharose 31-40 cyclin dependent kinase 2 Homo sapiens 9-13 8078506-0 1994 Changes of G1 cyclins, cdk2, and cyclin A during the differentiation of HL60 cells induced by TPA. Tetradecanoylphorbol Acetate 94-97 cyclin dependent kinase 2 Homo sapiens 23-27 8078506-5 1994 TPA-treated cells accumulated in G1 phase within 24 h and most of the cells were arrested in this phase at 36 h. The expression of cyclins and cdk2 was studied by Northern blot hybridization of the reverse-transcription polymerase chain reaction (RT-PCR). Tetradecanoylphorbol Acetate 0-3 cyclin dependent kinase 2 Homo sapiens 143-147 8260651-10 1993 In addition, ligation of the IL-2R leads to rapid increases in myc expression and more delayed increases in the expression of the cdc2 and cdk2 kinases and the cyclins through a tyrosine phosphorylation independent pathway. Tyrosine 178-186 cyclin dependent kinase 2 Homo sapiens 139-143 8253384-0 1993 Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Rubidium 17-19 cyclin dependent kinase 2 Homo sapiens 62-66 8242751-4 1993 p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Rubidium 92-94 cyclin dependent kinase 2 Homo sapiens 48-52 8242751-4 1993 p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Rubidium 92-94 cyclin dependent kinase 2 Homo sapiens 107-111 8510751-2 1993 The crystal structures of the human CDK2 apoenzyme and its Mg2+ ATP complex have been determined to 2.4 A resolution. mg2+ atp 59-67 cyclin dependent kinase 2 Homo sapiens 36-40 8397206-7 1993 Glycerol gradient analyses demonstrated that the purified cdk2 (p33) protein co-sedimented with a cyclin A-dependent H1 kinase activity. Glycerol 0-8 cyclin dependent kinase 2 Homo sapiens 58-62 8397207-3 1993 Activation of cdk2-catalyzed H1 kinase activity by cyclin A required a 10-min preincubation of the two components, whereas cdc2 kinase supported phosphate incorporation without a detectable time lag upon the addition of cyclin B1, suggesting a slower association rate of cdk2 with cyclin A compared with cdc2 and cyclin B1. Phosphates 145-154 cyclin dependent kinase 2 Homo sapiens 14-18 8397207-4 1993 Both cdk2 and cyclin A, as well as cdc2 and cyclin B1, formed stable complexes in the absence of ATP and substrate that could be isolated after glycerol gradient centrifugation. Glycerol 144-152 cyclin dependent kinase 2 Homo sapiens 5-9 8443411-2 1993 Recent evidence indicates that cyclin-dependent kinase 2 (Cdk2), like its homolog Cdc2, requires cyclin binding and phosphorylation (of threonine-160) for activation in vivo. Threonine 136-145 cyclin dependent kinase 2 Homo sapiens 31-56 8463339-0 1993 G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. Nitrogen 20-28 cyclin dependent kinase 2 Homo sapiens 69-73 8475101-7 1993 Tryptic peptide mapping demonstrated that Cdc25M2 treatment of cyclin A or cyclin B1 immune complexes resulted in the specific dephosphorylation of Thr-14 and Tyr-15 on CDK2 or CDC2, respectively. Threonine 148-151 cyclin dependent kinase 2 Homo sapiens 169-173 8443411-2 1993 Recent evidence indicates that cyclin-dependent kinase 2 (Cdk2), like its homolog Cdc2, requires cyclin binding and phosphorylation (of threonine-160) for activation in vivo. Threonine 136-145 cyclin dependent kinase 2 Homo sapiens 58-62 1372993-4 1992 We have found that CDK2 encodes a 33-kDa cyclin A-associated protein kinase that contains phosphotyrosine, two characteristics it shares with CDC2Hs. Phosphotyrosine 90-105 cyclin dependent kinase 2 Homo sapiens 19-23 1396589-5 1992 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. Acid Red 374 15-19 cyclin dependent kinase 2 Homo sapiens 66-70 1396589-5 1992 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. Alanine 25-32 cyclin dependent kinase 2 Homo sapiens 66-70 33921173-10 2021 The findings indicate that the pharmacological action of PG against GC might be associated with the regulation of three core targets: HSP90AA1, CDK2, and MMP1. pg 57-59 cyclin dependent kinase 2 Homo sapiens 144-148 33806566-5 2021 Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. betulinic acid 13-15 cyclin dependent kinase 2 Homo sapiens 96-127 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. evodiamine 180-190 cyclin dependent kinase 2 Homo sapiens 265-269 9407975-0 1997 Correspondence re: G. Palumbo et al., the tyrphostin AG17 induces apoptosis and inhibition of cdk2 activity in a lymphoma cell line that overexpresses bcl-2. Tyrphostins 42-52 cyclin dependent kinase 2 Homo sapiens 94-98 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. gamma-sitosterol 192-207 cyclin dependent kinase 2 Homo sapiens 265-269 34942456-10 2022 Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). zjc 27-30 cyclin dependent kinase 2 Homo sapiens 154-158 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. Berberine 212-221 cyclin dependent kinase 2 Homo sapiens 265-269 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. zjc 118-121 cyclin dependent kinase 2 Homo sapiens 265-269 34708431-0 2022 Dieckol induces cell cycle arrest by down-regulating CDK2/cyclin E in response to p21/p53 activation in human tracheal fibroblasts. dieckol 0-7 cyclin dependent kinase 2 Homo sapiens 53-57 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. Quercetin 130-139 cyclin dependent kinase 2 Homo sapiens 265-269 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. (R)-Canadine 141-153 cyclin dependent kinase 2 Homo sapiens 265-269 34942456-12 2022 CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. palmatine 155-164 cyclin dependent kinase 2 Homo sapiens 265-269 34896440-9 2022 Knockdown of Cx43 attenuated the TCE-induced cell hyper-proliferation and CDK2 upregulation. Trichloroethylene 33-36 cyclin dependent kinase 2 Homo sapiens 74-78 34896440-11 2022 In conclusion, TCE exposure resulted in upregulation of Cx43 via Akt phosphorylation, consequently stimulated CDK2 expression, contributing to hyper-proliferation in hESCs. Trichloroethylene 15-18 cyclin dependent kinase 2 Homo sapiens 110-114 34708431-2 2022 However, the role of dieckol in cyclin-dependent kinase 2 (CDK2)/cyclin E signalling, which regulates fibrosis development, has not yet been determined. dieckol 21-28 cyclin dependent kinase 2 Homo sapiens 32-57 34708431-2 2022 However, the role of dieckol in cyclin-dependent kinase 2 (CDK2)/cyclin E signalling, which regulates fibrosis development, has not yet been determined. dieckol 21-28 cyclin dependent kinase 2 Homo sapiens 59-63 34708431-5 2022 The results showed that dieckol had significant anti-proliferative activity against Hs680.Tr human tracheal fibroblastsWestern blotting analysis also found that dieckol dose-dependently induced the cell cycle arrest of Hs680.Tr fibroblasts in the G0/G1 phase, accompanied by the downregulation of CDK2 and cyclin E and the upregulation of p21 and p53. dieckol 24-31 cyclin dependent kinase 2 Homo sapiens 297-301 34708431-5 2022 The results showed that dieckol had significant anti-proliferative activity against Hs680.Tr human tracheal fibroblastsWestern blotting analysis also found that dieckol dose-dependently induced the cell cycle arrest of Hs680.Tr fibroblasts in the G0/G1 phase, accompanied by the downregulation of CDK2 and cyclin E and the upregulation of p21 and p53. dieckol 161-168 cyclin dependent kinase 2 Homo sapiens 297-301 34884975-6 2021 As expected, CDK4 and CDK6, the two G0-G1 phase promoting kinases as well as CDK2, a key G1-S phase transition promoting kinase, were significantly downregulated with (20S) G-Rh2 treatment, and these downregulations were mediated by the proteasome pathway. ginsenoside Rh2 173-178 cyclin dependent kinase 2 Homo sapiens 77-81 34962586-4 2021 The aim of the study has been on the eugenol compounds, which has potent actions on Eralpha, PR, EGFR, CDK2, mTOR, ERBB2, c-Src, HSP90, and chemokines receptors inhibition. Eugenol 37-44 cyclin dependent kinase 2 Homo sapiens 103-107 34820007-6 2022 Isoliensinine was found to induce cell cycle arrest at the G0/G1 phase by upregulating p21 expression and downregulating CDK2 and cyclin E in breast cancer cells. isoliensinine 0-13 cyclin dependent kinase 2 Homo sapiens 121-125 34880385-0 2021 Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway. tanshinone 0-14 cyclin dependent kinase 2 Homo sapiens 90-94 34696683-7 2021 Ropivacaine challenge also arrested cells in the G2 phase, followed by a decline in the protein expression of cyclin D1 and cyclin-dependent kinase 2, and an increase in p27 levels in HepG2 cells. Ropivacaine 0-11 cyclin dependent kinase 2 Homo sapiens 124-149 34688130-0 2021 Synthesis of a new series of pyrazolo(1,5-a)pyrimidines as CDK2 inhibitors and anti-leukemia. pyrazolo(1,5-a)pyrimidine 29-55 cyclin dependent kinase 2 Homo sapiens 59-63 34688130-1 2021 Based on the structural study of previously known CDK2 inhibitors, a new series of pyrazolo(1,5-a)pyrimidine derivatives was designed and synthesized. pyrazolo(1,5-a)pyrimidine 83-108 cyclin dependent kinase 2 Homo sapiens 50-54 34688130-3 2021 The 7-(4-Bromo-phenyl)-3-(3-chloro/2-chloro-phenylazo)-pyrazolo(1,5-a)pyrimidin-2-ylamines 5 h and 5i revealed the best CDK2 inhibitory activity with comparable potency (IC50 = 22 and 24 nM, respectively) to that of dinaciclib (IC50 = 18 nM). 7-(4-bromo-phenyl)-3-(3-chloro/2-chloro-phenylazo)-pyrazolo(1,5-a)pyrimidin-2-ylamines 4-90 cyclin dependent kinase 2 Homo sapiens 120-124 34688130-3 2021 The 7-(4-Bromo-phenyl)-3-(3-chloro/2-chloro-phenylazo)-pyrazolo(1,5-a)pyrimidin-2-ylamines 5 h and 5i revealed the best CDK2 inhibitory activity with comparable potency (IC50 = 22 and 24 nM, respectively) to that of dinaciclib (IC50 = 18 nM). dinaciclib 216-226 cyclin dependent kinase 2 Homo sapiens 120-124 34688130-10 2021 The molecular docking simulations indicated, as expected, that the dinaciclib analogues can well-accommodate the CDK2 binding site, forming a variety of interactions. dinaciclib 67-77 cyclin dependent kinase 2 Homo sapiens 113-117 34551654-6 2021 As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. quinazolin-4(3h) 21-37 cyclin dependent kinase 2 Homo sapiens 200-204 33327806-0 2021 Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3beta inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies. 2-oxindole 6-14 cyclin dependent kinase 2 Homo sapiens 52-56 33327806-0 2021 Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3beta inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies. benzofuran 15-25 cyclin dependent kinase 2 Homo sapiens 52-56 33327806-1 2021 The serine/threonine protein kinases CDK2 and GSK-3beta are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3beta inhibitors targeting breast cancer (5a-g, 7a-h, and 13a-b). Serine 4-10 cyclin dependent kinase 2 Homo sapiens 37-41 33327806-1 2021 The serine/threonine protein kinases CDK2 and GSK-3beta are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3beta inhibitors targeting breast cancer (5a-g, 7a-h, and 13a-b). 2-oxindole 153-161 cyclin dependent kinase 2 Homo sapiens 37-41 33327806-1 2021 The serine/threonine protein kinases CDK2 and GSK-3beta are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3beta inhibitors targeting breast cancer (5a-g, 7a-h, and 13a-b). 2-oxindole 153-161 cyclin dependent kinase 2 Homo sapiens 219-223 33327806-1 2021 The serine/threonine protein kinases CDK2 and GSK-3beta are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3beta inhibitors targeting breast cancer (5a-g, 7a-h, and 13a-b). benzofuran 162-172 cyclin dependent kinase 2 Homo sapiens 37-41 33327806-1 2021 The serine/threonine protein kinases CDK2 and GSK-3beta are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3beta inhibitors targeting breast cancer (5a-g, 7a-h, and 13a-b). benzofuran 162-172 cyclin dependent kinase 2 Homo sapiens 219-223 34658297-0 2021 Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo. polyphyllin I 0-13 cyclin dependent kinase 2 Homo sapiens 112-116 34658297-7 2021 Mechanistically, PPI can inhibit Rb through the p21/CDK2/Rb signaling pathway in NSCLC. Rubidium 33-35 cyclin dependent kinase 2 Homo sapiens 52-56 34154478-8 2021 These preliminary results suggested that compounds 16a,b,d could serve as promising lead compounds for the future development of new potent anticancer agents.HighlightsTwo new series of pyrrolizines bearing 3,4,5-trimethoxyphenyl moieties were synthesized.Compounds 16a,b,d displayed the highest cytotoxicity against the three cancer cell lines.Kinase profiling test revealed inhibition of multiple oncogenic kinases by compounds 16a,b,d.Compounds 16a,b,d exhibited weak to moderate inhibition of tubulin-polymerization.Compounds 16a,b,d induced preG1 and G2/M cell cycle arrest and early apoptosis in MCF-7 cells.Docking studies revealed high binding affinities for compounds 16a,b towards tubulin and CDK-2. pyrrolizines 186-198 cyclin dependent kinase 2 Homo sapiens 703-708 34551654-7 2021 Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. quinazolin-4(3h) 42-58 cyclin dependent kinase 2 Homo sapiens 199-203 34551654-7 2021 Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. Adenosine Triphosphate 153-156 cyclin dependent kinase 2 Homo sapiens 199-203 33327806-6 2021 The most potent compounds 5d-f caused cell cycle arrest in the G2/M phase in MCF-7 cells inducing cell apoptosis because of the CDK2/GSK-3beta inhibition. 5d-f 26-30 cyclin dependent kinase 2 Homo sapiens 128-132 34791641-5 2022 In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-alpha and TRPV1 and induced cell cycle arrest in the S phase with cyclin A2/CDK2 downregulation. (+)-(R)-2-(3,4-dimethoxyphenyl)pyrrolidine 14-20 cyclin dependent kinase 2 Homo sapiens 153-157 33327806-7 2021 Molecular docking studies showed that the newly synthesised N1 -unsubstituted oxindole hybrids have comparable binding patterns in both CDK2 and GSK-3beta. n1 -unsubstituted oxindole 60-86 cyclin dependent kinase 2 Homo sapiens 136-140 33327806-8 2021 The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3beta. 2-oxindole 4-12 cyclin dependent kinase 2 Homo sapiens 176-180 33327806-8 2021 The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3beta. Hydrogen 74-82 cyclin dependent kinase 2 Homo sapiens 176-180 34884480-2 2021 Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. 2,6,9-trisubstituted purines 42-70 cyclin dependent kinase 2 Homo sapiens 24-28 34884480-2 2021 Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. Water 157-162 cyclin dependent kinase 2 Homo sapiens 24-28 34884480-5 2021 We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. Purines 110-117 cyclin dependent kinase 2 Homo sapiens 168-172 34555628-1 2021 New diphenyl-1H-pyrazoles were synthesized and screened for CDK2 inhibition where 8d, 9b, 9c, and 9e exhibited promising activity (IC50 = 51.21, 41.36, 29.31, and 40.54 nM respectively) compared to R-Roscovitine (IC50 = 43.25 nM). diphenyl-1h-pyrazoles 4-25 cyclin dependent kinase 2 Homo sapiens 60-64 34619160-0 2021 A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling. cinobufagin 75-86 cyclin dependent kinase 2 Homo sapiens 147-151 34619160-5 2021 Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells. cinobufagin 131-142 cyclin dependent kinase 2 Homo sapiens 22-26 34619160-7 2021 Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. CVT 313 56-63 cyclin dependent kinase 2 Homo sapiens 41-45 34619160-7 2021 Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. cinobufagin 111-122 cyclin dependent kinase 2 Homo sapiens 41-45 34619160-8 2021 Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC. cinobufagin 45-56 cyclin dependent kinase 2 Homo sapiens 105-109 34782853-6 2021 Shikonin arrested H1299 cell cycle at the G0/G1 phase by regulating CDK/cyclin family members. shikonin 0-8 cyclin dependent kinase 2 Homo sapiens 68-71 34612580-4 2021 Here, we demonstrate that the phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to make its DSB repair pathway choice between NHEJ and HR. Serine 64-70 cyclin dependent kinase 2 Homo sapiens 56-60 34612580-6 2021 The CDK2 phosphorylation on serine 426 stabilizes WRN"s affinity for RPA, likely increasing its long-range resection at the end of DNA strands, which is a crucial step for HR. Serine 28-34 cyclin dependent kinase 2 Homo sapiens 4-8 34555628-1 2021 New diphenyl-1H-pyrazoles were synthesized and screened for CDK2 inhibition where 8d, 9b, 9c, and 9e exhibited promising activity (IC50 = 51.21, 41.36, 29.31, and 40.54 nM respectively) compared to R-Roscovitine (IC50 = 43.25 nM). Roscovitine 198-211 cyclin dependent kinase 2 Homo sapiens 60-64 34555628-5 2021 Screening the synthesized compounds 8a-c for inhibition of CDK isoforms revealed that compound 8a exhibited nearly equal inhibition to all the tested CDK isoforms, while compound 8b inhibits CDK4/D1 preferentially than the other isoforms and compound 8c inhibits CDK1, CDK2 and CDK4 more than CDK7. 8a-c 36-40 cyclin dependent kinase 2 Homo sapiens 269-273 34555628-8 2021 Docking to CDK2 ATP binding site revealed similar interactions as the co-crystallized ligand R-Roscovitine (PDB code; 3ddq). Adenosine Triphosphate 16-19 cyclin dependent kinase 2 Homo sapiens 11-15 34555628-8 2021 Docking to CDK2 ATP binding site revealed similar interactions as the co-crystallized ligand R-Roscovitine (PDB code; 3ddq). Roscovitine 93-106 cyclin dependent kinase 2 Homo sapiens 11-15 34423559-0 2021 Structural and binding studies of Cyclin dependent kinase 2 with NU6140 inhibitor. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 65-71 cyclin dependent kinase 2 Homo sapiens 34-59 34423559-2 2021 Reported inhibitors of CDK2 target the ATP-binding pocket to inhibit the kinase activity. Adenosine Triphosphate 39-42 cyclin dependent kinase 2 Homo sapiens 23-27 34423559-4 2021 NU6140 is a CDK2 inhibitor with moderate potency and selectivity. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 0-6 cyclin dependent kinase 2 Homo sapiens 12-16 34423559-5 2021 Herein we report the co-crystal structure determination of NU6140 in complex with CDK2 and confirmation of the binding using various biophysical methods. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 59-65 cyclin dependent kinase 2 Homo sapiens 82-86 34423559-6 2021 Our data shows that NU6140 bind to CDK2 with a Kd of 800 nM as determined by SPR and stabilizes the protein against thermal denaturation (DeltaTm- 5 C). 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 20-26 cyclin dependent kinase 2 Homo sapiens 35-39 34423559-8 2021 Based on these data, we propose structural modifications of NU6140 to introduce new interactions with CDK2 that can improve its potency while retaining the selectivity. 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide 60-66 cyclin dependent kinase 2 Homo sapiens 102-106 34446542-2 2021 Here we describe a novel strategy to prevent CDK4i resistance by using a therapeutic liposomal:peptide formulation, NP-ALT, to inhibit the tyrosine phosphorylation of p27Kip1(CDKN1B), which in turn inhibits both CDK4/6 and CDK2. Tyrosine 139-147 cyclin dependent kinase 2 Homo sapiens 223-227 34446542-9 2021 Implications: This study reveals that blocking p27 tyrosine phosphorylation inhibits CDK4 and CDK2 activity and induces ROS-dependent necroptosis, suggesting a novel therapeutic option for endocrine and CDK4 inhibitor-resistant HR+ tumors. Tyrosine 51-59 cyclin dependent kinase 2 Homo sapiens 94-98 34455222-8 2021 Furthermore, THP-1/ox-LDL Exo significantly increased the expression levels of CDK2 and proliferative cell nuclear antigen in human VSMCs, while these effects were reversed following LIPCAR silencing. lipcar 183-189 cyclin dependent kinase 2 Homo sapiens 79-83 34303663-6 2021 Pimozide induced G1 cell cycle arrest concomitant with the upregulation of p21/p27/p53, and suppression of cyclin D2/E, cyclin-dependent kinase 2/4/6 and c-Myc expression, and pRb phosphorylation. Pimozide 0-8 cyclin dependent kinase 2 Homo sapiens 120-149 34506738-4 2021 They identify the cyclin E-CDK2 axis and Myc signaling as key pathways of resistance and develop PF-06873600, a selective CDK2/4/6 inhibitor. PF-06873600 97-108 cyclin dependent kinase 2 Homo sapiens 122-130 34520734-4 2021 We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. PF-06873600 49-60 cyclin dependent kinase 2 Homo sapiens 116-124 34520734-4 2021 We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. pf3600 62-68 cyclin dependent kinase 2 Homo sapiens 116-124 34520734-4 2021 We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. pyrido(3,2-d)pyrimidine 73-89 cyclin dependent kinase 2 Homo sapiens 116-124 34638959-4 2021 Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. morusin 10-17 cyclin dependent kinase 2 Homo sapiens 114-139 34703821-5 2021 During the differentiation process that induced manifestation of breast cancer stem-like cells, DS significantly inhibited mammosphere formation in a dose-dependent manner and increased the expression of p53 and p21 in breast cancer stem-like cells, reducing the expression of cdc2 and cyclin B1 in MDA-MB-231 cells and cyclin D, cyclin E, CDK4, and CDK2 in MCF-7 cells. dioscin 96-98 cyclin dependent kinase 2 Homo sapiens 350-354 34639115-6 2021 It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27Kip1 expression in HaCaT cells. lysophosphatidic acid 18-21 cyclin dependent kinase 2 Homo sapiens 112-142 34098069-3 2021 Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Cadmium 0-2 cyclin dependent kinase 2 Homo sapiens 152-156 34638959-4 2021 Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. morusin 10-17 cyclin dependent kinase 2 Homo sapiens 141-145 34273487-3 2021 In this study, we investigated the rational design of a series of bivalent triazine-based derivatives with the aim of simultaneously targeting the active site and the remote hotspot critical for the interaction with CDK2/CycA. Triazines 75-83 cyclin dependent kinase 2 Homo sapiens 216-220 34676031-0 2021 Sulfonylamide Compounds as CDK2 Inhibitors for Treating Cancer. Sulfanilamide 0-13 cyclin dependent kinase 2 Homo sapiens 27-31 34479917-9 2021 Paclitaxel induced cell cycle arrest at the G1 phase in response to DNA damage, in association with the suppression of CDC25A, Cdk2 and Cyclin E1 protein expression. Paclitaxel 0-10 cyclin dependent kinase 2 Homo sapiens 127-131 34091175-2 2021 We have designed alkyl and aryl substituted isatin-triazole ligands and performed molecular docking to rank and predict possible binding pockets in CDK2 and EGFR kinases. isatin-triazole 44-59 cyclin dependent kinase 2 Homo sapiens 148-152 34146662-7 2021 Also, atrazine blocked the NSC cell cycle G1 phase via down-regulating CCND1, CDK2, and CDK4, with no obvious effect on apoptosis. Atrazine 6-14 cyclin dependent kinase 2 Homo sapiens 78-82 34365958-13 2022 CONCLUSION: The prepared styrylpyrazoles showed inhibition activity towards CDKs and can provide a novel chemotype of kinase inhibitors. styrylpyrazoles 25-40 cyclin dependent kinase 2 Homo sapiens 76-80 34340691-14 2021 La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. lanthanum(3+) 0-4 cyclin dependent kinase 2 Homo sapiens 181-185 34340691-14 2021 La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. ce3+ 6-10 cyclin dependent kinase 2 Homo sapiens 181-185 34340691-14 2021 La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. Fluorine 16-17 cyclin dependent kinase 2 Homo sapiens 181-185 34413960-3 2021 To test this possibility, we developed a series of CDK2-targeting N-acyl-N-alkylsulfonamide (NASA)-containing acylation probes. n-acyl-n-alkylsulfonamide 66-91 cyclin dependent kinase 2 Homo sapiens 51-55 34409029-12 2021 Through Oncomine, TIMER, UALCAN, PrognoScan databases, the expression level of CDK2 in LUAD was higher than normal tissues. oncomine 8-16 cyclin dependent kinase 2 Homo sapiens 79-83 34413960-3 2021 To test this possibility, we developed a series of CDK2-targeting N-acyl-N-alkylsulfonamide (NASA)-containing acylation probes. nasa 93-97 cyclin dependent kinase 2 Homo sapiens 51-55 34413960-5 2021 We determined that upon target binding, NASA-mediated reaction resulted in selective functionalization of Lys89 on purified or native CDK2. nasa 40-44 cyclin dependent kinase 2 Homo sapiens 134-138 34110834-0 2021 Discovery of PF-06873600, a CDK2/4/6 Inhibitor for the Treatment of Cancer. PF-06873600 13-24 cyclin dependent kinase 2 Homo sapiens 28-36 34230455-0 2021 Correction to: Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML. CYC065 55-66 cyclin dependent kinase 2 Homo sapiens 38-44 34243605-0 2021 Pyrazole ring-containing isolongifolanone derivatives as potential CDK2 inhibitors: Evaluation of anticancer activity and investigation of action mechanism. pyrazole 0-8 cyclin dependent kinase 2 Homo sapiens 67-71 34243605-0 2021 Pyrazole ring-containing isolongifolanone derivatives as potential CDK2 inhibitors: Evaluation of anticancer activity and investigation of action mechanism. Isolongifolanone 25-41 cyclin dependent kinase 2 Homo sapiens 67-71 34243605-8 2021 Docking results showed that compound 3b could bind well with CDK2 by forming hydrogen bonds with amino acid residues (LYS89 and HIS84). Hydrogen 77-85 cyclin dependent kinase 2 Homo sapiens 61-65 34206976-0 2021 Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity. pyrazolopyridine 17-33 cyclin dependent kinase 2 Homo sapiens 77-81 34156324-3 2021 Activation of CDK2 requires dephosphorylation of tyrosine-15 by CDC25A. Tyrosine 49-57 cyclin dependent kinase 2 Homo sapiens 14-18 33715669-3 2021 The UV-radiated reduced-TiO2 suppressed the cell proliferation by inhibiting the expression of cell cycle kinase, cyclin dependent kinase 2 (Cdk2), and its functional regulators Cyclin E and Cyclin B1 as well as proliferation-regulating proteins of p85 regulatory sub-unit of phosphoinositide3-kinases (PI3K p85), phosphorylated protein kinase B (p-AKT/p-PKB) and phosphorylated mammalian target of rapamycin (p-mTOR). titanium dioxide 24-28 cyclin dependent kinase 2 Homo sapiens 141-145 34206976-0 2021 Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity. furo(3,2-b)pyridine 35-47 cyclin dependent kinase 2 Homo sapiens 77-81 34206976-0 2021 Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity. pyridine 53-61 cyclin dependent kinase 2 Homo sapiens 77-81 34130570-6 2021 Residue-based free energy decomposition method was further utilized to decode the contributions of a single residue to binding of inhibitors, and it was found that three inhibitors not only produce hydrogen bonding interactions and hydrophobic interactions with key residues of CDK2, which promotes binding of three inhibitors to CDK2, but also share similar binding modes. Hydrogen 198-206 cyclin dependent kinase 2 Homo sapiens 278-282 34151738-3 2021 Herein, we built a structure-based pharmacophore model complementing the ATP pocket site of CDK2 with four pharmacophoric features, using a series of structures obtained from cluster analysis during MD simulation assessment. Adenosine Triphosphate 73-76 cyclin dependent kinase 2 Homo sapiens 92-96 34151738-6 2021 In filtering hits (10 compounds) via molecular docking against CDK2, Schinilenol with -8.1 kcal/mol fetched out as a best lead phytoinhibitor in the presence of standard drug (Dinaciclib). Schinilenol 69-80 cyclin dependent kinase 2 Homo sapiens 63-67 34151738-8 2021 Optimization, flexibility prediction and the stability of CDK2 in complex with the ligands were also ascertained by means of molecular dynamics for 50 ns, which further proposed schinilenol having better binding stability than dinaciclib with RMSD values ranging from 0.31 to 0.34 nm. Schinilenol 178-189 cyclin dependent kinase 2 Homo sapiens 58-62 34130570-6 2021 Residue-based free energy decomposition method was further utilized to decode the contributions of a single residue to binding of inhibitors, and it was found that three inhibitors not only produce hydrogen bonding interactions and hydrophobic interactions with key residues of CDK2, which promotes binding of three inhibitors to CDK2, but also share similar binding modes. Hydrogen 198-206 cyclin dependent kinase 2 Homo sapiens 330-334 35623140-6 2022 CDK2 inhibitory results of compounds 4f, 4g, 4h, and 4w showed IC50 at 59.43, 143.6, 27.42, and 61.63 nM respectively, while that of Sunitinib was 23.8 nM. 4h 45-47 cyclin dependent kinase 2 Homo sapiens 0-4 34112754-0 2021 Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML. CYC065 40-51 cyclin dependent kinase 2 Homo sapiens 23-29 34112754-3 2021 Fadraciclib (CYC065), a novel cyclin-dependent kinase (CDK) 2/9 inhibitor, has preclinical efficacy in AML. CYC065 0-11 cyclin dependent kinase 2 Homo sapiens 30-63 34122599-5 2021 Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. cinobufotalin 0-13 cyclin dependent kinase 2 Homo sapiens 255-259 34122599-5 2021 Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Gefitinib 28-37 cyclin dependent kinase 2 Homo sapiens 255-259 35614852-4 2022 p27 tyrosine phosphorylation, in response to mitogenic signalling, promotes activation of CyclinD/Cdk4 and CyclinA/Cdk2. Tyrosine 4-12 cyclin dependent kinase 2 Homo sapiens 115-119 35636125-0 2022 Discovery of novel benzofuro(3,2-b)quinoline derivatives as dual CDK2/Topo I inhibitors. benzofuro[3,2-b]quinoline 19-44 cyclin dependent kinase 2 Homo sapiens 65-69 35636125-3 2022 Herein, we describe our efforts toward the discovery of a series of benzofuro(3,2-b)quinoline alkaloid derivatives as CDK2 inhibitors through a scaffold hopping strategy. benzofuro(3,2-b)quinoline alkaloid 68-102 cyclin dependent kinase 2 Homo sapiens 118-122 35636125-5 2022 Resultantly, ZLHQ-5f exhibited promising anti-proliferative and CDK2 inhibitory activities. zlhq-5f 13-20 cyclin dependent kinase 2 Homo sapiens 64-68 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Serine 122-125 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Serine 122-125 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 192-218 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 192-218 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 220-224 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 220-224 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Acetates 246-253 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Acetates 246-253 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 275-279 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Dihydroxyacetone Phosphate 275-279 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Acetates 290-297 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. Acetates 290-297 cyclin dependent kinase 2 Homo sapiens 27-31 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. 1-acetyl-dhap 319-332 cyclin dependent kinase 2 Homo sapiens 0-25 34140692-5 2021 Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. 1-acetyl-dhap 319-332 cyclin dependent kinase 2 Homo sapiens 27-31 34248015-8 2021 Furthermore, CDK2 levels were markedly increased in hypoxic cells (P<0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P<0.05). 3,4-dihydroxyacetophenone 82-86 cyclin dependent kinase 2 Homo sapiens 115-119 35598793-0 2022 Development of Pyrazolo(3,4-d)pyrimidin-4-one Scaffold as novel CDK2 Inhibitors: Design, Synthesis, and Biological evaluation. pyrazolo[3,4-d]pyrimidin-4-one 15-45 cyclin dependent kinase 2 Homo sapiens 64-68 35598793-1 2022 A series of pyrazolo(3,4-d)pyrimidin-4-one scaffold were designed and synthesized as novel CDK2 inhibitors. pyrazolo[3,4-d]pyrimidin-4-one 12-42 cyclin dependent kinase 2 Homo sapiens 91-95 35483142-3 2022 Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Citrinin 9-17 cyclin dependent kinase 2 Homo sapiens 99-125 35483142-3 2022 Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Citrinin 9-17 cyclin dependent kinase 2 Homo sapiens 127-131 35623140-0 2022 Novel Azine Linked Hybrids of 2-Indolinone and Thiazolodinone Scaffolds as CDK2 Inhibitors with Potential Anticancer Activity: In Silico Design, Synthesis, Biological, Molecular Dynamics and Binding Free Energy Studies. pyridine 6-11 cyclin dependent kinase 2 Homo sapiens 75-79 35623140-0 2022 Novel Azine Linked Hybrids of 2-Indolinone and Thiazolodinone Scaffolds as CDK2 Inhibitors with Potential Anticancer Activity: In Silico Design, Synthesis, Biological, Molecular Dynamics and Binding Free Energy Studies. 2-oxindole 30-42 cyclin dependent kinase 2 Homo sapiens 75-79 35623140-0 2022 Novel Azine Linked Hybrids of 2-Indolinone and Thiazolodinone Scaffolds as CDK2 Inhibitors with Potential Anticancer Activity: In Silico Design, Synthesis, Biological, Molecular Dynamics and Binding Free Energy Studies. thiazolodinone 47-61 cyclin dependent kinase 2 Homo sapiens 75-79 35623140-3 2022 Docking studies in the active site of CDK2, one of the key checkpoints enzymes, revealed that the binding scores of the designed molecules are comparable to the reference enzyme"s inhibitors Sunitinib, Nintedanib, and Semaxanib. Sunitinib 191-200 cyclin dependent kinase 2 Homo sapiens 38-42 35623140-3 2022 Docking studies in the active site of CDK2, one of the key checkpoints enzymes, revealed that the binding scores of the designed molecules are comparable to the reference enzyme"s inhibitors Sunitinib, Nintedanib, and Semaxanib. nintedanib 202-212 cyclin dependent kinase 2 Homo sapiens 38-42 35623140-3 2022 Docking studies in the active site of CDK2, one of the key checkpoints enzymes, revealed that the binding scores of the designed molecules are comparable to the reference enzyme"s inhibitors Sunitinib, Nintedanib, and Semaxanib. Semaxinib 218-227 cyclin dependent kinase 2 Homo sapiens 38-42 35595767-2 2022 While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2 are ATP competitors that are either nonspecific or highly toxic, and typically fail clinical trials. Adenosine Triphosphate 94-97 cyclin dependent kinase 2 Homo sapiens 15-19 35595767-3 2022 One alternative approach is to develop non-ATP competitive inhibitors; they disrupt interactions between CDK2 and either its partners or substrates, resulting in specific inhibition of CDK2 activities. Adenosine Triphosphate 43-46 cyclin dependent kinase 2 Homo sapiens 185-189 35595767-2 2022 While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2 are ATP competitors that are either nonspecific or highly toxic, and typically fail clinical trials. Adenosine Triphosphate 94-97 cyclin dependent kinase 2 Homo sapiens 85-89 35595767-3 2022 One alternative approach is to develop non-ATP competitive inhibitors; they disrupt interactions between CDK2 and either its partners or substrates, resulting in specific inhibition of CDK2 activities. Adenosine Triphosphate 43-46 cyclin dependent kinase 2 Homo sapiens 105-109 35595767-6 2022 Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupts the interaction between CDK2 and cyclins. Homoharringtonine 21-38 cyclin dependent kinase 2 Homo sapiens 122-126 35595767-6 2022 Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupts the interaction between CDK2 and cyclins. Homoharringtonine 40-43 cyclin dependent kinase 2 Homo sapiens 122-126 35523987-6 2022 Through protein interaction (PPI), gene enrichment analysis, and gene difference analysis, one effective target of Selumetinib was finally screened, CDK2 mainly existing in the cytoplasm, endoplasmic reticulum, and plasma membrane; the target plays a role in the treatment of LGG by inhibiting the signal pathways of PI3K Akt and participating in biological processes such as peptide amino acid modification, regulation of intracellular signal transduction, and positive regulation of cell metabolism. AZD 6244 115-126 cyclin dependent kinase 2 Homo sapiens 149-153 35623141-0 2022 Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property. Tacrine 19-26 cyclin dependent kinase 2 Homo sapiens 79-83 35598400-5 2022 CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Cannabidiol 0-3 cyclin dependent kinase 2 Homo sapiens 168-193 35598400-5 2022 CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Cannabidiol 0-3 cyclin dependent kinase 2 Homo sapiens 195-199 35586682-11 2022 This regulatory effect was related to the expression regulation of HSP90AA1, CDK2, STAT3, and phosphor-STAT3 (p-STAT3) by YQYJ, kaempferol, and quercetin. kaempferol 128-138 cyclin dependent kinase 2 Homo sapiens 77-81 35586682-11 2022 This regulatory effect was related to the expression regulation of HSP90AA1, CDK2, STAT3, and phosphor-STAT3 (p-STAT3) by YQYJ, kaempferol, and quercetin. Quercetin 144-153 cyclin dependent kinase 2 Homo sapiens 77-81 35523987-7 2022 CDK2 may be a new direction of Selumetinib in the clinical treatment of LGG. AZD 6244 31-42 cyclin dependent kinase 2 Homo sapiens 0-4 35592410-0 2022 Structure-Based Design of 2-Aminopurine Derivatives as CDK2 Inhibitors for Triple-Negative Breast Cancer. 2-Aminopurine 26-39 cyclin dependent kinase 2 Homo sapiens 55-59 35592410-4 2022 Herein, we designed a new series of 2-aminopurine derivatives based on the fragment-centric pocket mapping analysis of CDK2 crystal structure. 2-Aminopurine 36-49 cyclin dependent kinase 2 Homo sapiens 119-123 35592410-5 2022 Our results indicated that the introduction of polar substitution at the C-6 position of purine would be beneficial for CDK2 inhibition. purine 89-95 cyclin dependent kinase 2 Homo sapiens 120-124 35450818-6 2022 Moreover, treatment with the mitochondrial complex IV inhibitor tetrathiomolybdate dramatically abrogated the promoting effect of STMP1 on cell proliferation and the expression of cyclin E2, CDK2 and E2F1. tetrathiomolybdate 64-82 cyclin dependent kinase 2 Homo sapiens 191-195 35631350-9 2022 Furthermore, HMN-214 induces apoptosis and significantly obstructs the cell cycle at the G2/M phase in NB cells by inhibiting multiple cell-cycle-related genes, such as PLK1, WEE1, CDK1, CDK2, Cyclin B1, CHK1, and CHK2. (E)-4-(2-(2-(N-acetyl-N-(4-methoxybenzenesulfonyl)amino)stilbazole)) 1-oxide 13-20 cyclin dependent kinase 2 Homo sapiens 187-191 35361964-19 2022 Such a role of RB supporting DREAM formation may be exerted by the RB-SKP2-p27-cyclin A/E-CDK2-p130-DREAM link. Rubidium 15-17 cyclin dependent kinase 2 Homo sapiens 90-94 35343565-4 2022 In non-transformed cells, p21 activates RB in G2 by inhibiting Cyclin D1-CDK2/CDK4. Rubidium 40-42 cyclin dependent kinase 2 Homo sapiens 73-77 35393397-4 2022 Furthermore, a series of experiments (luciferase reporter assay, RNA pull-down assay, and western blotting) showed that lncRNA-Gm3932 down-regulated Prc1 and Nuf2 by competitively sponging miR-344d-3-5p, which subsequently reduced the expression of cell cycle-related proteins CDK2, CDC2, and Cyclin B1, and increased the expression of P21 and P27. gm3932 127-133 cyclin dependent kinase 2 Homo sapiens 277-281 35235599-9 2022 BR2-2xPPD treatment induced cell cycle arrest by inhibiting the expression of cyclin D1 and CDK2 genes in EGFR-wild type A549 cells. br2-2xppd 0-9 cyclin dependent kinase 2 Homo sapiens 92-96 35356976-10 2022 Furthermore, a cyclin-dependent kinase-2 inhibitor suppressed the toxic actions of cisplatin on SGN-like cells in otic organoids. Cisplatin 83-92 cyclin dependent kinase 2 Homo sapiens 15-40 35124201-5 2022 6-Benzylaminopurines showed comparable CDK2 inhibitory activity to 6-anilinopurines, however, the PDGFRalpha and FLT3-ITD inhibition was strongly suppressed. benzylaminopurine 0-20 cyclin dependent kinase 2 Homo sapiens 39-43 35370663-10 2022 Astragalus polysaccharides has the characteristics of multi-targets and multi-pathways, and its mechanism of action may be through regulating the expression of VCAM1, RELA, CDK2, JUN, CDK1, HSP90AA1, NOS2, SOD1, CASP3, AHSA1, PTGER3 and other genes during the development of pulmonary fibrosis. astragalus polysaccharides 0-26 cyclin dependent kinase 2 Homo sapiens 173-177 35408446-0 2022 Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2. Triazoles 6-20 cyclin dependent kinase 2 Homo sapiens 160-165 35408446-0 2022 Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2. coumarin 21-29 cyclin dependent kinase 2 Homo sapiens 160-165 35408446-0 2022 Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2. Glycosides 37-47 cyclin dependent kinase 2 Homo sapiens 160-165 35408446-0 2022 Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2. tetrazolyl 58-68 cyclin dependent kinase 2 Homo sapiens 160-165 35246013-0 2022 6-Methoxyflavone induces S-phase arrest through the CCNA2/CDK2/p21CIP1 signaling pathway in HeLa cells. 6-methoxyflavone 0-16 cyclin dependent kinase 2 Homo sapiens 58-62 35246013-7 2022 Cell proliferation and cycle assays, transcriptome sequencing, polymerase chain reactions, and western blotting revealed that 6-methoxyflavone inhibited HeLa cell proliferation and induced S-phase arrest via the CCNA2/CDK2/ cyclin-dependent kinase inhibitor 1A (p21CIP1) pathway. 6-methoxyflavone 126-142 cyclin dependent kinase 2 Homo sapiens 218-222 35246013-8 2022 Molecular docking and noncovalent interaction analyses showed that 6-methoxyflavone had the strongest affinity toward, inhibitory effect on, and noncovalent interactions with CDK2, and that the combination of CDK2 and CCNA2 enhanced these effects. 6-methoxyflavone 67-83 cyclin dependent kinase 2 Homo sapiens 175-179 35246013-8 2022 Molecular docking and noncovalent interaction analyses showed that 6-methoxyflavone had the strongest affinity toward, inhibitory effect on, and noncovalent interactions with CDK2, and that the combination of CDK2 and CCNA2 enhanced these effects. 6-methoxyflavone 67-83 cyclin dependent kinase 2 Homo sapiens 209-213 35246013-10 2022 6-Methoxyflavone induces S-phase arrest in HeLa cells via the CCNA2/CDK2/p21CIP1 pathway. 6-methoxyflavone 0-16 cyclin dependent kinase 2 Homo sapiens 68-72 35386089-6 2022 VCD treatment significantly inhibited the expression of cyclin A and cyclin-dependent kinase 2 (CDK2). 4-vinyl-1-cyclohexene dioxide 0-3 cyclin dependent kinase 2 Homo sapiens 69-94 35091290-12 2022 Furthermore, inhibitory activity of compounds 5a, 5b, 5e1, 5m, 6f and 6j on CDK2 enzyme were tested and revealed that compound 6f, with the N-4-flourobenzyl- 2-oxindole and 3-p-chlorobenzylidene moieties, has a comparable inhibitory activity to the reference drug sunitinib. Sunitinib 264-273 cyclin dependent kinase 2 Homo sapiens 76-80 35091290-3 2022 Accordingly, the current work describes the structural based design of 3-arylidene-2-oxindole derivatives through docking of their structures in the active site of CDK2 as one of the dominant enzyme checkpoints. 3-arylidene-2-oxindole 71-93 cyclin dependent kinase 2 Homo sapiens 164-168 35091290-12 2022 Furthermore, inhibitory activity of compounds 5a, 5b, 5e1, 5m, 6f and 6j on CDK2 enzyme were tested and revealed that compound 6f, with the N-4-flourobenzyl- 2-oxindole and 3-p-chlorobenzylidene moieties, has a comparable inhibitory activity to the reference drug sunitinib. n-4-flourobenzyl- 2-oxindole 140-168 cyclin dependent kinase 2 Homo sapiens 76-80 35091290-12 2022 Furthermore, inhibitory activity of compounds 5a, 5b, 5e1, 5m, 6f and 6j on CDK2 enzyme were tested and revealed that compound 6f, with the N-4-flourobenzyl- 2-oxindole and 3-p-chlorobenzylidene moieties, has a comparable inhibitory activity to the reference drug sunitinib. 3-p-chlorobenzylidene 173-194 cyclin dependent kinase 2 Homo sapiens 76-80 35386089-6 2022 VCD treatment significantly inhibited the expression of cyclin A and cyclin-dependent kinase 2 (CDK2). 4-vinyl-1-cyclohexene dioxide 0-3 cyclin dependent kinase 2 Homo sapiens 96-100 35441158-7 2022 Multiple alterations in E2-mediated cell cycle control were identified in the endocrine-resistant cell lines including increased expression of MYC, cyclin A1, cyclin D1, cyclin-dependent kinase 1 (CDK1), CDK2, and hyperphosphorylated retinoblastoma protein (ppRb), whereas p21 and p27 were reduced. Estradiol 24-26 cyclin dependent kinase 2 Homo sapiens 204-208 35134436-6 2022 We demonstrate that the protein expression level of p21 was up-regulated, and CDK1/CDK2 were reduced significantly in both HCT 116 and SH-SY5Y cells after EG treatment. anthraglycoside B 155-157 cyclin dependent kinase 2 Homo sapiens 83-87 34747319-6 2022 Also, GA treatment significantly decreased the Bax/Bcl2 protein ratio and the expression of Cyclin D1, CDK2, CDK4, MMP-9, N-cadherin, and vimentin in SW620 and HT29 cells. Glycyrrhizic Acid 6-8 cyclin dependent kinase 2 Homo sapiens 103-107 35205737-0 2022 CRIF1-CDK2 Interface Inhibitors Enhance Taxol Inhibition of the Lethal Triple-Negative Breast Cancer. Paclitaxel 40-45 cyclin dependent kinase 2 Homo sapiens 6-10 35205737-8 2022 Overall, the resistance to the anti-proliferative effects induced by taxol can be significantly reduced by the combined treatment with selective CRIF1-CDK2 interface inhibitors, making a conceptual advance in the CDK-related cancer treatment. Paclitaxel 69-74 cyclin dependent kinase 2 Homo sapiens 151-155 35115540-3 2022 We show here that DENR is phosphorylated on Serine 73 by Cyclin B/CDK1 and Cyclin A/CDK2 at the onset of mitosis, and then dephosphorylated as cells exit mitosis. Serine 44-50 cyclin dependent kinase 2 Homo sapiens 84-88 35007525-7 2022 In addition, mollugin induced changes in cyclin A2 and CDK2. rubimaillin 13-21 cyclin dependent kinase 2 Homo sapiens 55-59 35377976-6 2022 The role of TPT1-AS1 and CDK2 in regulating the cell cycle progression and proliferation of SNU-398 and SU.86.86 cells was explored by cell cycle assay and cell proliferation assay, respectively. 4-(1H-Pyrrol-1-yl)aniline 92-95 cyclin dependent kinase 2 Homo sapiens 25-29 35007168-0 2022 Aaptamine derivatives with CDK2 inhibitory activities from the South China Sea sponge Aaptos suberitoides. aaptamine 0-9 cyclin dependent kinase 2 Homo sapiens 27-31 35053380-10 2022 As well-known CDK inhibitors, dinaciclib and kenpaullone stabilize PXR and result in elevated expression and activity of PXR-targeted DMETs, including carboxylesterases, CYP3A4 and P-gp. dinaciclib 30-40 cyclin dependent kinase 2 Homo sapiens 14-17 35053380-10 2022 As well-known CDK inhibitors, dinaciclib and kenpaullone stabilize PXR and result in elevated expression and activity of PXR-targeted DMETs, including carboxylesterases, CYP3A4 and P-gp. kenpaullone 45-56 cyclin dependent kinase 2 Homo sapiens 14-17 34711160-5 2022 Mostly pyrazole scaffolds have shown selectivity and potency for CDK2 inhibitors. pyrazole 7-15 cyclin dependent kinase 2 Homo sapiens 65-69