PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 9030780-10 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 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 34555628-8 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 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 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 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 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 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. 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. Roscovitine 24-35 cyclin dependent kinase 2 Homo sapiens 55-59 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 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 32433863-3 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 17713901-5 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 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 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 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 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 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 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 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 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 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 16770643-4 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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. Roscovitine 0-11 cyclin dependent kinase 2 Homo sapiens 91-95 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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. Roscovitine 106-117 cyclin dependent kinase 2 Homo sapiens 44-48 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. 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. 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 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 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 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