PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 34735897-5 2022 Clonogenic survival and Annexin V assays demonstrated increased cell death with clofarabine and pictilisib combination treatment (P<0.01). Clofarabine 80-91 annexin A5 Homo sapiens 24-33 34133426-11 2021 In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation. Clofarabine 33-44 salt inducible kinase 1 Homo sapiens 63-66 34133426-11 2021 In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation. Clofarabine 33-44 cAMP responsive element binding protein 1 Homo sapiens 72-76 34133426-0 2021 Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. Clofarabine 0-11 mitogen-activated protein kinase 1 Homo sapiens 20-23 34133426-11 2021 In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation. Clofarabine 33-44 CD99 molecule (Xg blood group) Homo sapiens 101-105 34133426-0 2021 Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. Clofarabine 0-11 salt inducible kinase 1 Homo sapiens 24-27 33262250-9 2021 Clofarabine and cladribine were ENT1 and ENT2 substrates, while nevirapine and lexibulin were ENT1 and ENT2 non-transported inhibitors. Clofarabine 0-11 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 32-36 34133426-0 2021 Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. Clofarabine 0-11 cAMP responsive element binding protein 1 Homo sapiens 28-32 34133426-0 2021 Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. Clofarabine 0-11 CD99 molecule (Xg blood group) Homo sapiens 63-67 34133426-3 2021 We demonstrated that clofarabine may have a novel function though inhibiting CD99, a transmembrane protein highly expressed on Ewing Sarcoma (ES) cells. Clofarabine 21-32 CD99 molecule (Xg blood group) Homo sapiens 77-81 34133426-5 2021 Here we present additional data to support the hypothesis that clofarabine acts on CD99 and regulates key signaling pathways in ES. Clofarabine 63-74 CD99 molecule (Xg blood group) Homo sapiens 83-87 34133426-6 2021 Cellular thermal shift assay indicated a direct interaction between clofarabine and CD99 in ES cell lysates. Clofarabine 68-79 CD99 molecule (Xg blood group) Homo sapiens 84-88 34133426-9 2021 CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. Clofarabine 21-32 CD99 molecule (Xg blood group) Homo sapiens 0-4 34133426-9 2021 CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. Clofarabine 21-32 mitogen-activated protein kinase 1 Homo sapiens 91-94 34133426-9 2021 CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. Clofarabine 21-32 salt inducible kinase 1 Homo sapiens 96-99 34133426-9 2021 CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. Clofarabine 21-32 cAMP responsive element binding protein 1 Homo sapiens 105-109 34133426-11 2021 In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation. Clofarabine 33-44 mitogen-activated protein kinase 1 Homo sapiens 58-61 32097280-1 2021 OBJECTIVE: The objective of this study was to report the case of a girl diagnosed as suffering from multisystem, BRAF V600E-positive refractory Langerhans cell histiocytosis (LCH) and coexistent Erdheim-Chester disease (ECD) with perirenal, intracranial involvement and the dramatic response to clofarabine treatment. Clofarabine 295-306 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 113-117 33262250-9 2021 Clofarabine and cladribine were ENT1 and ENT2 substrates, while nevirapine and lexibulin were ENT1 and ENT2 non-transported inhibitors. Clofarabine 0-11 solute carrier family 29 member 2 Homo sapiens 41-45 30544666-0 2018 Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells. Clofarabine 6-17 retinoic acid receptor beta Homo sapiens 80-107 33291877-1 2020 To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Clofarabine 213-224 phosphodiesterase 8A Homo sapiens 101-121 33291877-1 2020 To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Clofarabine 213-224 phosphodiesterase 8A Homo sapiens 123-128 31999420-1 2020 Clofarabine (2-chloro-2"-fluoro-2"-deoxyarabinosyladenine, ClF), a second-generation 2"-deoxyadenosine analog, possesses manifold anti-cancer activities. Clofarabine 0-11 CLQTL1 Homo sapiens 59-62 30417868-7 2018 As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Clofarabine 235-246 deoxycytidine kinase Homo sapiens 291-311 30417868-7 2018 As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Clofarabine 235-246 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 313-316 29473342-0 2018 Clofarabine exerts antileukemic activity against cytarabine-resistant B-cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression. Clofarabine 0-11 deoxycytidine kinase Homo sapiens 125-145 30176535-4 2018 The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 muM (vs. 3.8 muM) on purified protein and 0.24 muM (vs. 23.6 muM) on CD73 expressed on cells. Clofarabine 4-15 latexin Homo sapiens 103-106 30176535-4 2018 The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 muM (vs. 3.8 muM) on purified protein and 0.24 muM (vs. 23.6 muM) on CD73 expressed on cells. Clofarabine 4-15 latexin Homo sapiens 116-119 30176535-4 2018 The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 muM (vs. 3.8 muM) on purified protein and 0.24 muM (vs. 23.6 muM) on CD73 expressed on cells. Clofarabine 4-15 latexin Homo sapiens 116-119 30176535-4 2018 The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 muM (vs. 3.8 muM) on purified protein and 0.24 muM (vs. 23.6 muM) on CD73 expressed on cells. Clofarabine 4-15 latexin Homo sapiens 116-119 30176535-4 2018 The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 muM (vs. 3.8 muM) on purified protein and 0.24 muM (vs. 23.6 muM) on CD73 expressed on cells. Clofarabine 4-15 5'-nucleotidase ecto Homo sapiens 172-176 29473342-12 2018 In contrast to Ara-C, although the knockout of DCK induced marked resistance to clofarabine, sensitivity to clofarabine was only marginally associated with DCK gene expression level, suggesting a possible efficacy of clofarabine for BCP-ALL that shows relative Ara-C resistance due to low DCK expression. Clofarabine 80-91 deoxycytidine kinase Homo sapiens 47-50 29382926-0 2018 Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99. Clofarabine 0-11 CD99 molecule (Xg blood group) Homo sapiens 106-110 29382926-6 2018 A membrane-impermeable analog of clofarabine showed similar cytotoxicity in culture, suggesting that it can function through inhibiting CD99 independent of DNA metabolism. Clofarabine 33-44 CD99 molecule (Xg blood group) Homo sapiens 136-140 29382926-8 2018 Our findings provide a novel molecular mechanism for clofarabine that involves direct binding to a cell surface receptor CD99 and inhibiting its biological activities. Clofarabine 53-64 CD99 molecule (Xg blood group) Homo sapiens 121-125 28049642-9 2017 In the subgroup analyses, clofarabine improved overall survival and EFS for European Leukemia Net (ELN) 2010 intermediate I prognostic risk AML (EFS, 26% +- 4 vs 40% +- 5 at 4 years; Cox P = .002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% +- 5 vs 40% +- 7; Cox P < .001). Clofarabine 26-37 nucleophosmin 1 Homo sapiens 236-240 29174506-2 2018 Herein, we identified that clofarabine (4), an FDA-approved drug, displayed potential PDE2 inhibitory activity (IC50 = 3.12 +- 0.67 muM) by structure-based virtual screening and bioassay. Clofarabine 27-38 latexin Homo sapiens 132-135 28442502-7 2017 Clofarabine, a purine nucleoside analogue that inhibits RRM1, induced growth arrest and apoptosis in p53 wild-type cell lines. Clofarabine 0-11 ribonucleotide reductase catalytic subunit M1 Homo sapiens 56-60 28442502-7 2017 Clofarabine, a purine nucleoside analogue that inhibits RRM1, induced growth arrest and apoptosis in p53 wild-type cell lines. Clofarabine 0-11 tumor protein p53 Homo sapiens 101-104 28624910-8 2017 RR1 inhibitors that have long been used in chemotherapy such as gemcitabine, cladribine, fludarabine and clofarabine are currently used mostly as a combination therapy, but are equally efficacious as a monotherapy, except tezacitabine which did not progress beyond phase I trials. Clofarabine 105-116 ribonucleotide reductase catalytic subunit M1 Homo sapiens 0-3 29634384-0 2018 Inhibition of breast cancer cell growth by the combination of clofarabine and sulforaphane involves epigenetically mediated CDKN2A upregulation. Clofarabine 62-73 cyclin dependent kinase inhibitor 2A Homo sapiens 124-130 29634384-4 2018 In the present study, using methylation-sensitive restriction analysis (MSRA) and qPCR, we showed that clofarabine in combination with sulforaphane, a phytochemical from cruciferous vegetables, significantly reactivates DNA methylation-silenced CDKN2A tumour suppressor and inhibits cancer cell growth at a non-invasive breast cancer stage. Clofarabine 103-114 cyclin dependent kinase inhibitor 2A Homo sapiens 245-251 28436707-4 2017 Expanding the clinically relevant substrates of SAMHD1, we demonstrate that THP-1 CRISPR/Cas9 cells lacking a functional SAMHD1 gene showed increased sensitivity to the antimetabolites nelarabine, fludarabine, decitabine, vidarabine, clofarabine, and trifluridine. Clofarabine 234-245 SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 Homo sapiens 48-54 28436707-4 2017 Expanding the clinically relevant substrates of SAMHD1, we demonstrate that THP-1 CRISPR/Cas9 cells lacking a functional SAMHD1 gene showed increased sensitivity to the antimetabolites nelarabine, fludarabine, decitabine, vidarabine, clofarabine, and trifluridine. Clofarabine 234-245 GLI family zinc finger 2 Homo sapiens 76-81 28436707-4 2017 Expanding the clinically relevant substrates of SAMHD1, we demonstrate that THP-1 CRISPR/Cas9 cells lacking a functional SAMHD1 gene showed increased sensitivity to the antimetabolites nelarabine, fludarabine, decitabine, vidarabine, clofarabine, and trifluridine. Clofarabine 234-245 SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 Homo sapiens 121-127 28049642-9 2017 In the subgroup analyses, clofarabine improved overall survival and EFS for European Leukemia Net (ELN) 2010 intermediate I prognostic risk AML (EFS, 26% +- 4 vs 40% +- 5 at 4 years; Cox P = .002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% +- 5 vs 40% +- 7; Cox P < .001). Clofarabine 26-37 fms related receptor tyrosine kinase 3 Homo sapiens 251-255 28012306-0 2017 Interaction of anticancer drug clofarabine with human serum albumin and human alpha-1 acid glycoprotein. Clofarabine 31-42 albumin Homo sapiens 60-67 28012306-2 2017 The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins found abundantly in human plasma, Human Serum Albumin (HSA) and alpha-1 acid glycoprotein (AAG) was investigated by spectroscopic and molecular modeling methods. Clofarabine 32-43 albumin Homo sapiens 149-162 25656700-4 2015 In vitro studies using the wild type recombinant cN-II demonstrated that fludarabine inhibited enzymatic activity in a mixed manner (Ki 0.5 mM and Ki" 9 mM), whereas no inhibition was observed with clofarabine and cladribine. Clofarabine 198-209 5'-nucleotidase, cytosolic II Homo sapiens 49-54 27294334-9 2016 We propose the following mechanisms of synergism: Flu, Clo and Rom induce histone modifications and chromatin remodeling, exposing DNA to Bu alkylation; the increased production of ROS, due to drug-mediated stress response and decreased GSH, damages the MM causing leakage of pro-apoptotic factors; down-regulation of MRP1 increases intracellular Bu concentration and exacerbates the DDR; and inhibition of multiple survival pathways. Clofarabine 55-58 ATP binding cassette subfamily C member 1 Homo sapiens 318-322 26819918-0 2015 Clofarabine Has Apoptotic Effect on T47D Breast Cancer Cell Line via P53R2 Gene Expression. Clofarabine 0-11 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 69-74 26819918-2 2015 Clofarabine-induced defect in DNA replication, induces p53 and subsequently P53R2 genes as subunit of RR. Clofarabine 0-11 tumor protein p53 Homo sapiens 55-58 26819918-2 2015 Clofarabine-induced defect in DNA replication, induces p53 and subsequently P53R2 genes as subunit of RR. Clofarabine 0-11 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 76-81 26819918-3 2015 clofarabine deregulated P53R2 gene expression leading to the elevated levels of P53R2 which impose resistance to DNA damaging drugs. Clofarabine 0-11 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 24-29 26819918-3 2015 clofarabine deregulated P53R2 gene expression leading to the elevated levels of P53R2 which impose resistance to DNA damaging drugs. Clofarabine 0-11 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 80-85 26819918-8 2015 Moreover, after treating with clofarabine the apoptotic and necrotic cells were detected using Annexin V and propodium iodide (PI) reagents by flowcytometry technique. Clofarabine 30-41 annexin A5 Homo sapiens 95-104 26462050-4 2015 In a screen against compounds that are classified as inhibitors of DNA repair or synthesis, the reporter generation was exquisitely sensitive to ribonucleotide reductase (RNR) inhibitors such as gemcitabine and clofarabine, but not to inhibitors of PARP, ATR, ATM, Chk1, and others. Clofarabine 211-222 ATR serine/threonine kinase Homo sapiens 255-258 26462050-4 2015 In a screen against compounds that are classified as inhibitors of DNA repair or synthesis, the reporter generation was exquisitely sensitive to ribonucleotide reductase (RNR) inhibitors such as gemcitabine and clofarabine, but not to inhibitors of PARP, ATR, ATM, Chk1, and others. Clofarabine 211-222 ATM serine/threonine kinase Homo sapiens 260-263 26462050-4 2015 In a screen against compounds that are classified as inhibitors of DNA repair or synthesis, the reporter generation was exquisitely sensitive to ribonucleotide reductase (RNR) inhibitors such as gemcitabine and clofarabine, but not to inhibitors of PARP, ATR, ATM, Chk1, and others. Clofarabine 211-222 checkpoint kinase 1 Homo sapiens 265-269 26188848-0 2015 The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia. Clofarabine 17-28 lysine methyltransferase 2A Homo sapiens 32-35 26188848-5 2015 Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Clofarabine 73-84 lysine methyltransferase 2A Homo sapiens 89-92 26188848-7 2015 Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ~25 nM. Clofarabine 42-53 lysine methyltransferase 2A Homo sapiens 83-86 26188848-9 2015 Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Clofarabine 41-52 fragile histidine triad diadenosine triphosphatase Homo sapiens 128-132 26188848-9 2015 Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Clofarabine 41-52 fragile histidine triad diadenosine triphosphatase Homo sapiens 134-157 26188848-9 2015 Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Clofarabine 41-52 lysine methyltransferase 2A Homo sapiens 196-199 26188848-11 2015 We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. Clofarabine 17-28 lysine methyltransferase 2A Homo sapiens 80-83 25704054-6 2015 At lower concentrations of Clad/Clo, Flu, and Bu, inclusion of Pano and DAC enhanced cell killing, increased histone modifications and DNA demethylation, and increased the levels of P16/INK4a, P15/INK4b and P21/Waf1/Cip1 proteins. Clofarabine 32-35 F-box and WD repeat domain containing 4 Homo sapiens 72-75 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 F-box and WD repeat domain containing 4 Homo sapiens 71-74 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 secreted frizzled related protein 1 Homo sapiens 134-139 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 dickkopf WNT signaling pathway inhibitor 3 Homo sapiens 141-145 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 WNT inhibitory factor 1 Homo sapiens 151-155 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 catenin beta 1 Homo sapiens 182-194 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 52-55 F-box and WD repeat domain containing 4 Homo sapiens 231-234 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 220-223 secreted frizzled related protein 1 Homo sapiens 134-139 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 220-223 WNT inhibitory factor 1 Homo sapiens 151-155 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 220-223 catenin beta 1 Homo sapiens 182-194 25704054-7 2015 The observed DNA demethylating activity of Clad and Clo may complement DAC activity; increase demethylation of the gene promoters for SFRP1, DKK3, and WIF1; and cause degradation of beta-catenin in cells exposed to Clad/Clo+Flu+Bu+DAC+Pano. Clofarabine 220-223 F-box and WD repeat domain containing 4 Homo sapiens 231-234 25461250-0 2015 Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase. Clofarabine 34-45 deoxycytidine kinase Homo sapiens 100-120 24924397-0 2015 Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation. Clofarabine 16-27 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 114-119 24924397-0 2015 Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation. Clofarabine 16-27 caspase 3 Homo sapiens 140-149 24924397-3 2015 Resveratrol and clofarabine induced down-regulation of Mcl-1 protein level in MSTO-211H cells. Clofarabine 16-27 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 55-60 25461250-6 2015 Next, we determined expression of deoxycytidine kinase (dCK), which phosphorylates clofarabine to exert cytotoxicity, in clofarabine-sensitive and -resistant cells. Clofarabine 83-94 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 56-59 25461250-6 2015 Next, we determined expression of deoxycytidine kinase (dCK), which phosphorylates clofarabine to exert cytotoxicity, in clofarabine-sensitive and -resistant cells. Clofarabine 83-94 deoxycytidine kinase Homo sapiens 34-54 25461250-6 2015 Next, we determined expression of deoxycytidine kinase (dCK), which phosphorylates clofarabine to exert cytotoxicity, in clofarabine-sensitive and -resistant cells. Clofarabine 121-132 deoxycytidine kinase Homo sapiens 34-54 25461250-6 2015 Next, we determined expression of deoxycytidine kinase (dCK), which phosphorylates clofarabine to exert cytotoxicity, in clofarabine-sensitive and -resistant cells. Clofarabine 121-132 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 56-59 25111583-6 2014 The FLT3-ITD substrate STAT5 and its target gene PIM 2 product decreased when cells were exposed to Sor alone, Bu+Clo+Flu, and Bu+Clo+Flu+Sor. Clofarabine 114-117 fms related receptor tyrosine kinase 3 Homo sapiens 4-8 25461250-7 2015 Clofarabine-resistant cells showed significantly decreased expression of dCK RNA when compared with sensitive cells. Clofarabine 0-11 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 73-76 25111583-7 2014 The level of the proapoptotic protein p53 upregulated modulator of apoptosis (PUMA) increased, whereas the level of prosurvival protein MCL-1 decreased when cells were exposed to Bu+Clo+Flu+Sor. Clofarabine 182-185 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 136-141 25111583-8 2014 The interactions of PUMA with MCL-1 and/or BCL-2 were enhanced when cells were exposed to Bu+Clo+Flu or Bu+Clo+Flu+Sor. Clofarabine 93-96 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 30-35 25111583-8 2014 The interactions of PUMA with MCL-1 and/or BCL-2 were enhanced when cells were exposed to Bu+Clo+Flu or Bu+Clo+Flu+Sor. Clofarabine 93-96 BCL2 apoptosis regulator Homo sapiens 43-48 25111583-10 2014 Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Clofarabine 3-6 cytochrome c, somatic Homo sapiens 87-99 25111583-10 2014 Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Clofarabine 3-6 diablo IAP-binding mitochondrial protein Homo sapiens 101-150 25111583-6 2014 The FLT3-ITD substrate STAT5 and its target gene PIM 2 product decreased when cells were exposed to Sor alone, Bu+Clo+Flu, and Bu+Clo+Flu+Sor. Clofarabine 114-117 signal transducer and activator of transcription 5A Homo sapiens 23-28 25111583-10 2014 Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Clofarabine 3-6 diablo IAP-binding mitochondrial protein Homo sapiens 152-156 25111583-10 2014 Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Clofarabine 3-6 diablo IAP-binding mitochondrial protein Homo sapiens 158-196 25111583-10 2014 Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Clofarabine 3-6 diablo IAP-binding mitochondrial protein Homo sapiens 198-204 25111583-11 2014 Analogous, synergistic cytotoxicity in response to Bu, Clo, Flu, and Sor was observed in mononuclear cells isolated from FLT3-ITD-positive AML patients. Clofarabine 55-58 fms related receptor tyrosine kinase 3 Homo sapiens 121-125 25111583-6 2014 The FLT3-ITD substrate STAT5 and its target gene PIM 2 product decreased when cells were exposed to Sor alone, Bu+Clo+Flu, and Bu+Clo+Flu+Sor. Clofarabine 114-117 Pim-2 proto-oncogene, serine/threonine kinase Homo sapiens 49-54 25111583-12 2014 Although our previous studies were aimed at standardizing the conditioning regimen, the new findings suggest that patients with abnormal expression of FLT3 might further benefit from individualizing treatment through the addition of Sor to Bu+Clo+Flu, thereby providing personalized pretransplantation therapy. Clofarabine 243-246 fms related receptor tyrosine kinase 3 Homo sapiens 151-155 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 ATM serine/threonine kinase Homo sapiens 172-175 25408576-0 2014 Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells. Clofarabine 97-108 BCL2 like 1 Homo sapiens 13-19 25408576-2 2014 In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Clofarabine 147-158 BCL2 like 1 Homo sapiens 53-59 25408576-3 2014 Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. Clofarabine 16-27 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 38-43 25408576-7 2014 Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma. Clofarabine 70-81 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 200-205 25408576-7 2014 Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma. Clofarabine 70-81 BCL2 like 1 Homo sapiens 210-216 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 checkpoint kinase 2 Homo sapiens 176-180 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 tumor protein p53 Homo sapiens 181-184 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 tumor protein p73 Homo sapiens 189-192 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 ATM serine/threonine kinase Homo sapiens 205-208 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 checkpoint kinase 2 Homo sapiens 209-213 24144307-5 2014 [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway. Clofarabine 7-10 cell division cycle 25C Homo sapiens 214-219 24144307-6 2014 The [Flu + Clo + Bu + SAHA] combination causes mitochondrial outer membrane permeabilization, leakage of cytochrome c and Smac/Diablo into the cytosol with caspase activation, and release of apoptosis-inducing factor (AIF) into the nucleus resulting in nuclear fragmentation and cell death. Clofarabine 11-14 cytochrome c, somatic Homo sapiens 105-117 24144307-6 2014 The [Flu + Clo + Bu + SAHA] combination causes mitochondrial outer membrane permeabilization, leakage of cytochrome c and Smac/Diablo into the cytosol with caspase activation, and release of apoptosis-inducing factor (AIF) into the nucleus resulting in nuclear fragmentation and cell death. Clofarabine 11-14 diablo IAP-binding mitochondrial protein Homo sapiens 122-126 24144307-6 2014 The [Flu + Clo + Bu + SAHA] combination causes mitochondrial outer membrane permeabilization, leakage of cytochrome c and Smac/Diablo into the cytosol with caspase activation, and release of apoptosis-inducing factor (AIF) into the nucleus resulting in nuclear fragmentation and cell death. Clofarabine 11-14 diablo IAP-binding mitochondrial protein Homo sapiens 127-133 24296317-1 2014 Clofarabine (2-chloro-2"-fluoro-2"-deoxyarabinosyladenine, ClF) is a second-generation 2"-deoxyadenosine analogue that is structurally related to cladribine (2-chloro-2"-deoxyadenosine, 2CdA) and fludarabine (9-beta-d-arabinosyl-2-fluoroadenine, F-ara-A). Clofarabine 0-11 CLQTL1 Homo sapiens 59-62 24440659-12 2014 Compared with day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Clofarabine 95-106 H2A.X variant histone Homo sapiens 46-50 24692694-1 2014 BACKGROUND/AIM: Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Clofarabine 16-27 deoxycytidine kinase Homo sapiens 202-222 24692694-1 2014 BACKGROUND/AIM: Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Clofarabine 16-27 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 224-227 24692694-1 2014 BACKGROUND/AIM: Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Clofarabine 16-27 deoxyguanosine kinase Homo sapiens 233-254 24692694-1 2014 BACKGROUND/AIM: Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Clofarabine 16-27 Diacyl glycerol kinase Drosophila melanogaster 256-259 24144836-0 2014 Sorafenib as monotherapy or in association with cytarabine and clofarabine for the treatment of relapsed/refractory FLT3 ITD-positive advanced acute myeloid leukemia. Clofarabine 63-74 fms related receptor tyrosine kinase 3 Homo sapiens 116-120 23421409-2 2013 CAFdA is then phosphorylated to the active metabolite CAFdA triphosphate (CAFdATP) by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Clofarabine 0-5 deoxycytidine kinase Homo sapiens 86-106 23720496-10 2013 siRNA knockdown of the top three genes (SETBP1, BAG3, KLHL6) in LCLs revealed altered susceptibility to clofarabine, confirming relevance. Clofarabine 104-115 SET binding protein 1 Homo sapiens 40-46 23720496-10 2013 siRNA knockdown of the top three genes (SETBP1, BAG3, KLHL6) in LCLs revealed altered susceptibility to clofarabine, confirming relevance. Clofarabine 104-115 BAG cochaperone 3 Homo sapiens 48-52 23720496-10 2013 siRNA knockdown of the top three genes (SETBP1, BAG3, KLHL6) in LCLs revealed altered susceptibility to clofarabine, confirming relevance. Clofarabine 104-115 kelch like family member 6 Homo sapiens 54-59 23648290-7 2013 Exposure of MM cells to [Gem+Clo] also decreased the level of ribosomal RNA (rRNA), which might have resulted in nucleolar stress, as reported previously, and caused a p53-dependent cell death. Clofarabine 29-32 tumor protein p53 Homo sapiens 168-171 23648290-8 2013 A reduction by approximately 50% in the cytotoxicity of Gem and Clo was observed in the presence of pifithrin alpha, a p53 inhibitor. Clofarabine 64-67 tumor protein p53 Homo sapiens 119-122 24413065-5 2014 Caspase 8-negative I9.2 cells were considerably more resistant to [Gem+Clo+Ed] than caspase 8-positive cells. Clofarabine 71-74 caspase 8 Homo sapiens 0-9 24413065-6 2014 In all three cell lines [Gem+Clo+Ed] decreased the level of phosphorylation of the pro-survival protein AKT and activated the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) stress signaling pathway, which in J45.01 cells resulted in the phosphorylation and heterodimerization of the transcription factors ATF2 and c-Jun. Clofarabine 29-32 AKT serine/threonine kinase 1 Homo sapiens 104-107 24413065-6 2014 In all three cell lines [Gem+Clo+Ed] decreased the level of phosphorylation of the pro-survival protein AKT and activated the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) stress signaling pathway, which in J45.01 cells resulted in the phosphorylation and heterodimerization of the transcription factors ATF2 and c-Jun. Clofarabine 29-32 Jun proto-oncogene, AP-1 transcription factor subunit Homo sapiens 158-163 24413065-6 2014 In all three cell lines [Gem+Clo+Ed] decreased the level of phosphorylation of the pro-survival protein AKT and activated the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) stress signaling pathway, which in J45.01 cells resulted in the phosphorylation and heterodimerization of the transcription factors ATF2 and c-Jun. Clofarabine 29-32 activating transcription factor 2 Homo sapiens 325-329 24413065-6 2014 In all three cell lines [Gem+Clo+Ed] decreased the level of phosphorylation of the pro-survival protein AKT and activated the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) stress signaling pathway, which in J45.01 cells resulted in the phosphorylation and heterodimerization of the transcription factors ATF2 and c-Jun. Clofarabine 29-32 Jun proto-oncogene, AP-1 transcription factor subunit Homo sapiens 334-339 24239893-4 2014 Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO-211H cells, but not in normal mesothelial MeT-5A cells. Clofarabine 33-44 tumor protein p53 Homo sapiens 138-141 24239893-4 2014 Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO-211H cells, but not in normal mesothelial MeT-5A cells. Clofarabine 33-44 tumor protein p53 Homo sapiens 145-148 24239893-10 2014 Taken together, these results demonstrate that resveratrol and clofarabine synergistically elicit apoptotic signal via a p53-dependent pathway, and provide a scientific rationale for clinical evaluation of resveratrol as a promising chemopotentiator in MM. Clofarabine 63-74 tumor protein p53 Homo sapiens 121-124 23421409-2 2013 CAFdA is then phosphorylated to the active metabolite CAFdA triphosphate (CAFdATP) by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Clofarabine 0-5 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 108-111 23421409-2 2013 CAFdA is then phosphorylated to the active metabolite CAFdA triphosphate (CAFdATP) by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Clofarabine 0-5 deoxyguanosine kinase Homo sapiens 117-138 23421409-2 2013 CAFdA is then phosphorylated to the active metabolite CAFdA triphosphate (CAFdATP) by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Clofarabine 0-5 Diacyl glycerol kinase Drosophila melanogaster 140-143 23421409-11 2013 In addition, the two variants were resistant to CAFdA-induced apoptosis due to Bcl2 overexpression and decreased Bim. Clofarabine 48-53 BCL2 apoptosis regulator Homo sapiens 79-83 23421409-12 2013 A Bcl2 inhibitor, ABT737, acted synergistically with CAFdA to inhibit the growth with combination index values of 0.27 in HL/CAFdA20 and 0.23 in HL/CAFdA80, compared with 0.65 in HL-60. Clofarabine 53-58 BCL2 apoptosis regulator Homo sapiens 2-6 23187004-0 2012 Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation. Clofarabine 73-84 NFE2 like bZIP transcription factor 2 Homo sapiens 110-114 23246163-0 2013 Epstein-Barr virus-induced CD30-positive diffuse large B-cell lymphoma in a patient with mixed-phenotypic leukemia treated with clofarabine. Clofarabine 128-139 TNF receptor superfamily member 8 Homo sapiens 27-31 23628030-2 2013 The expression of Beclin 1 in U937 treated by clofarabine for 48h was measured by Western blot. Clofarabine 46-57 beclin 1 Homo sapiens 18-26 23628030-5 2013 Meanwhile the Beclin 1 was upregulated along with increase of clofarabine concentration, as compared with control group, the difference was statistically significant (P < 0.05). Clofarabine 62-73 beclin 1 Homo sapiens 14-22 23628030-6 2013 It is concluded that the different concentrations of clofarabine can significantly inhibit the proliferation of U937 in dose-dependent manner, and the mechanism of autophagic cell death in U937 may be associated with the upregulation of Beclin 1 expression. Clofarabine 53-64 beclin 1 Homo sapiens 237-245 22488775-9 2012 Clofarabine and VPA cooperate in inducing DNA DSBs, accompanied by Bax activation and apoptosis in pediatric AML cells. Clofarabine 0-11 BCL2 associated X, apoptosis regulator Homo sapiens 67-70 23187004-2 2012 To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. Clofarabine 174-185 NFE2 like bZIP transcription factor 2 Homo sapiens 69-73 23187004-6 2012 Altogether, these results suggest that the synergistic cytotoxic effect of clofarabine and resveratrol was mediated, at least in part, through suppression of Nrf2 signaling. Clofarabine 75-86 NFE2 like bZIP transcription factor 2 Homo sapiens 158-162 23146690-7 2013 Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma. Clofarabine 107-118 AKT serine/threonine kinase 1 Homo sapiens 150-153 23271044-4 2012 In this study, we assessed the therapeutic potential of a combination consisting of temsirolimus [an allosteric mTOR complex 1 (mTORC1) inhibitor] with clofarabine, a nucleoside analogue with potent inhibitory effects on both ribonucleotide reductase and DNA polymerase. Clofarabine 152-163 CREB regulated transcription coactivator 1 Mus musculus 128-134 22490700-5 2012 Here, we show that the S74E mutation increased the k(cat) for cladribine (CdA) by 8- or 3-fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine (CAFdA) by about 2-fold with both ATP and UTP, and for fludarabine (F-Ara-A) by 2-fold, but only with UTP. Clofarabine 158-169 cytidine deaminase Homo sapiens 74-77 22884950-0 2012 Synergism between clofarabine and decitabine through p53R2: a pharmacodynamic drug-drug interaction modeling. Clofarabine 18-29 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 53-58 22884950-1 2012 Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotidereductase, p53R2. Clofarabine 0-11 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 141-146 22884950-1 2012 Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotidereductase, p53R2. Clofarabine 13-16 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 141-146 22884950-4 2012 These results confirm a role for p53R2 in both CLO and DEC mechanism of action, demonstrate synergism between these two drugs in this AML model and support the use of this combination in a future clinical trial. Clofarabine 47-50 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 33-38 22490700-5 2012 Here, we show that the S74E mutation increased the k(cat) for cladribine (CdA) by 8- or 3-fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine (CAFdA) by about 2-fold with both ATP and UTP, and for fludarabine (F-Ara-A) by 2-fold, but only with UTP. Clofarabine 171-176 cytidine deaminase Homo sapiens 74-77 22739157-5 2012 It is concluded that clofarabine inhibits proliferation of NB4 cells, which may be related with the down-regulation of Bcl-2 and induction of apoptosis. Clofarabine 21-32 BCL2 apoptosis regulator Homo sapiens 119-124 22739157-4 2012 After treated with clofarabine for 24 h, apoptosis rate of NB4 cells increased and Bcl-2 expression in NB4 cells decreased obviously (P < 0.05). Clofarabine 19-30 BCL2 apoptosis regulator Homo sapiens 83-88 22302964-6 2012 A cell viability assay was used to determine the sensitivity of the isogenic cell lines to the dCK-dependent NA prodrugs gemcitabine and clofarabine. Clofarabine 137-148 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 95-98 22285911-5 2012 In addition to the ABCC subfamily members, ABCG2 has been shown to transport nucleoside drugs and nucleoside-monophosphate derivatives of clinically relevant nucleoside drugs such as cytarabine, cladribine, and clofarabine to name a few. Clofarabine 211-222 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 43-48 22302964-8 2012 RESULTS: dCK and CDA activities measured by kinase and tracer uptake assays correlated with the sensitivity of isogenic cell lines to gemcitabine and clofarabine. Clofarabine 150-161 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 9-12 22302964-8 2012 RESULTS: dCK and CDA activities measured by kinase and tracer uptake assays correlated with the sensitivity of isogenic cell lines to gemcitabine and clofarabine. Clofarabine 150-161 cytidine deaminase Mus musculus 17-20 22302964-11 2012 (18)F-FAC and l-(18)F-FMAC PET estimates of the enzymatic activities of dCK and CDA in tumor implants in mice were predictive of responses to gemcitabine and clofarabine treatment in vivo. Clofarabine 158-169 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 72-75 22302964-11 2012 (18)F-FAC and l-(18)F-FMAC PET estimates of the enzymatic activities of dCK and CDA in tumor implants in mice were predictive of responses to gemcitabine and clofarabine treatment in vivo. Clofarabine 158-169 cytidine deaminase Mus musculus 80-83 21245102-0 2011 Deoxycytidine kinase modulates the impact of the ABC transporter ABCG2 on clofarabine cytotoxicity. Clofarabine 74-85 deoxycytidine kinase Homo sapiens 0-20 21848522-0 2011 Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Clofarabine 0-11 colony stimulating factor 3 Homo sapiens 81-86 21127859-2 2011 dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Clofarabine 123-134 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 0-3 20965266-3 2011 We conducted a phase I trial to determine the maximum tolerated dose (MTD) of clofarabine in combination with high-dose etoposide and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with refractory non-Hodgkin lymphoma (NHL). Clofarabine 78-89 metallothionein 1E Homo sapiens 70-73 21245102-0 2011 Deoxycytidine kinase modulates the impact of the ABC transporter ABCG2 on clofarabine cytotoxicity. Clofarabine 74-85 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 65-70 21245102-4 2011 Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. Clofarabine 8-19 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 25-28 21245102-4 2011 Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. Clofarabine 8-19 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 77-80 21245102-4 2011 Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. Clofarabine 8-19 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 77-80 21245102-4 2011 Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. Clofarabine 8-19 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 166-171 21245102-4 2011 Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. Clofarabine 195-206 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 166-171 21245102-5 2011 We show that ABCG2 influence on clofarabine cytotoxicity was markedly influenced by dCK activity. Clofarabine 32-43 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 13-18 21245102-5 2011 We show that ABCG2 influence on clofarabine cytotoxicity was markedly influenced by dCK activity. Clofarabine 32-43 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 84-87 21245102-6 2011 When dCK expression was reduced by siRNA, clofarabine cytotoxicity was strongly reduced by enhanced ABCG2-mediated efflux. Clofarabine 42-53 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 5-8 21245102-6 2011 When dCK expression was reduced by siRNA, clofarabine cytotoxicity was strongly reduced by enhanced ABCG2-mediated efflux. Clofarabine 42-53 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 100-105 21245102-7 2011 Conversely, dCK overexpression blunted ABCG2-mediated efflux of clofarabine by increasing the formation of clofarabine nucleotides. Clofarabine 64-75 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 12-15 21245102-7 2011 Conversely, dCK overexpression blunted ABCG2-mediated efflux of clofarabine by increasing the formation of clofarabine nucleotides. Clofarabine 64-75 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 39-44 21245102-8 2011 The use of an ABCG2 inhibitor confirmed that ABCG2 export of clofarabine is maximal when dCK levels are minimal. Clofarabine 61-72 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 14-19 21245102-8 2011 The use of an ABCG2 inhibitor confirmed that ABCG2 export of clofarabine is maximal when dCK levels are minimal. Clofarabine 61-72 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 45-50 21245102-8 2011 The use of an ABCG2 inhibitor confirmed that ABCG2 export of clofarabine is maximal when dCK levels are minimal. Clofarabine 61-72 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 89-92 21245102-9 2011 Analysis of intracellular clofarabine metabolites suggested that ABCG2 exported clofarabine more readily than clofarabine monophosphate. Clofarabine 26-37 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 65-70 21245102-9 2011 Analysis of intracellular clofarabine metabolites suggested that ABCG2 exported clofarabine more readily than clofarabine monophosphate. Clofarabine 80-91 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 65-70 21245102-10 2011 That ABCG2 primarily effluxes clofarabine, but not chlorfarabine-monophosphate, was confirmed by HPLC analysis of drug exported from ABCG2-overexpressing cells. Clofarabine 30-41 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 5-10 21245102-10 2011 That ABCG2 primarily effluxes clofarabine, but not chlorfarabine-monophosphate, was confirmed by HPLC analysis of drug exported from ABCG2-overexpressing cells. Clofarabine 30-41 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 133-138 21245102-11 2011 Because the level and function of dCK and ABCG2 vary substantially among other types of cancer, these findings have important implications not only for clofarabine therapy but for purine nucleoside therapy in general. Clofarabine 152-163 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 34-37 21245102-11 2011 Because the level and function of dCK and ABCG2 vary substantially among other types of cancer, these findings have important implications not only for clofarabine therapy but for purine nucleoside therapy in general. Clofarabine 152-163 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 42-47 18765824-2 2008 In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. Clofarabine 134-145 ATP binding cassette subfamily G member 2 (Junior blood group) Mus musculus 87-92 20933509-0 2011 The synergistic cytotoxicity of clofarabine, fludarabine and busulfan in AML cells involves ATM pathway activation and chromatin remodeling. Clofarabine 32-43 ATM serine/threonine kinase Homo sapiens 92-95 20933509-5 2011 The [Clo+Flu+Bu] combination activates an intense DNA damage response through the ATM pathway, leading to cell cycle checkpoint activation and apoptosis. Clofarabine 5-8 ATM serine/threonine kinase Homo sapiens 82-85 20933509-6 2011 Phosphorylations of SMC1 and SMC3, and methylations of histones 3 and 4, are much more pronounced in cells exposed to [Clo+Flu+Bu] than [Clo+Flu], suggesting their relevance in the efficacy of the triple-drug combination. Clofarabine 119-122 structural maintenance of chromosomes 1A Homo sapiens 20-24 20933509-6 2011 Phosphorylations of SMC1 and SMC3, and methylations of histones 3 and 4, are much more pronounced in cells exposed to [Clo+Flu+Bu] than [Clo+Flu], suggesting their relevance in the efficacy of the triple-drug combination. Clofarabine 119-122 structural maintenance of chromosomes 3 Homo sapiens 29-33 20933509-6 2011 Phosphorylations of SMC1 and SMC3, and methylations of histones 3 and 4, are much more pronounced in cells exposed to [Clo+Flu+Bu] than [Clo+Flu], suggesting their relevance in the efficacy of the triple-drug combination. Clofarabine 137-140 structural maintenance of chromosomes 1A Homo sapiens 20-24 20933509-6 2011 Phosphorylations of SMC1 and SMC3, and methylations of histones 3 and 4, are much more pronounced in cells exposed to [Clo+Flu+Bu] than [Clo+Flu], suggesting their relevance in the efficacy of the triple-drug combination. Clofarabine 137-140 structural maintenance of chromosomes 3 Homo sapiens 29-33 21131780-6 2010 We observed specific ablation of the mixed function DNA glycosylase/lyase Neil1 phenotypically enhanced several inhibitors of thymidine biosynthesis, as well as cellular phenotypes downstream of gemcitabine, cytarabine and clofarabine exposure. Clofarabine 223-234 nei like DNA glycosylase 1 Homo sapiens 74-79 19934300-0 2009 Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine. Clofarabine 109-120 fms related receptor tyrosine kinase 3 Homo sapiens 63-67 19934300-3 2009 We show defects in the response of mutant FLT3 AML cells to the S-phase drug clofarabine that could account for the apparent contradiction. Clofarabine 77-88 fms related receptor tyrosine kinase 3 Homo sapiens 42-46 19934300-5 2009 RESULTS: When treated with a short pulse of clofarabine, FLT3-ITD-harboring MOLM-13 and MV4.11 cells undergo similar damage levels (gammaH2AX foci) to wild-type cells but have a better repair capability than wild-type cells. Clofarabine 44-55 fms related receptor tyrosine kinase 3 Homo sapiens 57-61 19934300-8 2009 This loss is reduced or absent in clofarabine-treated FLT3 mutant cells. Clofarabine 34-45 fms related receptor tyrosine kinase 3 Homo sapiens 54-58 19934300-10 2009 Primary FLT3-ITD samples from untreated patients also display impaired cell cycle arrest and show enhanced sensitivity on prolonged treatment with clofarabine compared with wild-type samples. Clofarabine 147-158 fms related receptor tyrosine kinase 3 Homo sapiens 8-12 19934300-11 2009 CONCLUSION: There is a reversal of phenotype in mutant FLT3 cells dependent on the length of exposure to clofarabine. Clofarabine 105-116 fms related receptor tyrosine kinase 3 Homo sapiens 55-59 19741725-5 2009 The RP2Ds of clofarabine, cyclophosphamide and etoposide were 40, 440 and 100 mg/m(2)/day, respectively. Clofarabine 13-24 RP2 activator of ARL3 GTPase Homo sapiens 4-7 21115912-0 2010 Influence of clofarabine on transcriptional activity of PTEN, APC, RARB2, ZAP70 genes in K562 cells. Clofarabine 13-24 phosphatase and tensin homolog Homo sapiens 56-60 21115912-0 2010 Influence of clofarabine on transcriptional activity of PTEN, APC, RARB2, ZAP70 genes in K562 cells. Clofarabine 13-24 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 74-79 21115912-1 2010 BACKGROUND: In this study, the effect of clofarabine, a new generation 2"-deoxyadenosine analogue, on promoter methylation and transcriptional activity of selected genes (PTEN, APC, RARB2, ZAP70) in K562 cells was assessed. Clofarabine 41-52 phosphatase and tensin homolog Homo sapiens 171-175 21115912-1 2010 BACKGROUND: In this study, the effect of clofarabine, a new generation 2"-deoxyadenosine analogue, on promoter methylation and transcriptional activity of selected genes (PTEN, APC, RARB2, ZAP70) in K562 cells was assessed. Clofarabine 41-52 zeta chain of T cell receptor associated protein kinase 70 Homo sapiens 189-194 20347037-10 2010 The results suggest that clofarabine is a substrate for a cimetidine-sensitive organic cation transporter system in the kidney, presumably OCT2. Clofarabine 25-36 POU class 2 homeobox 2 Rattus norvegicus 139-143 19427036-1 2009 In this study, treatment of lymphoid tumor cells with low dose clofarabine upregulated the expression of Sp17 and SPAN-Xb. Clofarabine 63-74 sperm autoantigenic protein 17 Homo sapiens 105-109 19427036-1 2009 In this study, treatment of lymphoid tumor cells with low dose clofarabine upregulated the expression of Sp17 and SPAN-Xb. Clofarabine 63-74 SPANX family member B1 Homo sapiens 114-121 18765824-5 2008 The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors. Clofarabine 42-53 ATP binding cassette subfamily G member 2 (Junior blood group) Homo sapiens 57-62 18037589-8 2008 We also found that low doses of clofarabine can prolong the presence of radiation-induced gamma-H2AX nuclear focus formation, and high doses of clofarabine can induce DNA double-strand breaks, suggesting that clofarabine can interfere with DNA damage response pathways. Clofarabine 32-43 H2A.X variant histone Mus musculus 90-100 18600530-3 2008 SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. Clofarabine 99-104 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 35-38 18600530-5 2008 dGK depletion in cells resulted in lower sensitivity to FaraA, dFdC, CAFdA, and AraG, but slightly higher sensitivity to CdA and AraC. Clofarabine 69-74 Diacyl glycerol kinase Drosophila melanogaster 0-3 16234483-4 2006 Cells producing hENT1 or hCNT3 exhibited the highest uptake of Cl-F-ara-A, whereas nucleoside transport-deficient cells and cells producing hCNT1 lacked uptake altogether. Clofarabine 63-73 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 16-21 16421443-0 2006 The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Clofarabine 60-71 deoxycytidine kinase Homo sapiens 23-43 16421443-3 2006 Clofarabine is phosphorylated intracellularly by human deoxycytidine kinase (dCK) to the 5"-monophosphate, which is the rate-limiting step in activation of the prodrug. Clofarabine 0-11 deoxycytidine kinase Homo sapiens 55-75 16421443-3 2006 Clofarabine is phosphorylated intracellularly by human deoxycytidine kinase (dCK) to the 5"-monophosphate, which is the rate-limiting step in activation of the prodrug. Clofarabine 0-11 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 77-80 16421443-5 2006 As a purine-nucleoside analog, clofarabine is a better substrate of dCK than deoxycytidine. Clofarabine 31-42 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 68-71 16421443-10 2006 In the current study, the crystal structure of clofarabine- and ADP-bound dCK was solved to 2.55 angstroms by molecular replacement. Clofarabine 47-58 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 74-77 16421443-12 2006 The interactions between 2-Cl and its surrounding hydrophobic residues contribute to the high catalytic efficiency of dCK for clofarabine. Clofarabine 126-137 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 118-121 16234483-7 2006 The efficiency of Cl-F-ara-A transport by oocytes with recombinant transporters was hCNT3 > hENT2 > hENT1 > hCNT2; no transport was observed with hCNT1. Clofarabine 18-28 solute carrier family 29 member 2 Homo sapiens 95-100 17855478-1 2007 Deoxycytidine kinase (DCK) is a rate-limiting enzyme in the activation of nucleoside analogs such as cytarabine (ara-C), gemcitabine, clofarabine, and others. Clofarabine 134-145 deoxycytidine kinase Homo sapiens 0-20 17855478-1 2007 Deoxycytidine kinase (DCK) is a rate-limiting enzyme in the activation of nucleoside analogs such as cytarabine (ara-C), gemcitabine, clofarabine, and others. Clofarabine 134-145 deoxycytidine kinase Homo sapiens 22-25 16403905-10 2006 Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. Clofarabine 0-11 C-reactive protein Homo sapiens 72-74 16234483-7 2006 The efficiency of Cl-F-ara-A transport by oocytes with recombinant transporters was hCNT3 > hENT2 > hENT1 > hCNT2; no transport was observed with hCNT1. Clofarabine 18-28 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 106-111 16234483-7 2006 The efficiency of Cl-F-ara-A transport by oocytes with recombinant transporters was hCNT3 > hENT2 > hENT1 > hCNT2; no transport was observed with hCNT1. Clofarabine 18-28 solute carrier family 28 member 2 Homo sapiens 117-122 16234483-8 2006 Affinity studies with recombinant transporters produced in yeast showed that hENT1, hENT2, and hCNT3 all had higher affinities for Cl-F-ara-A than for either Cl-dAdo or F-ara-A. Clofarabine 131-141 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 77-82 16234483-8 2006 Affinity studies with recombinant transporters produced in yeast showed that hENT1, hENT2, and hCNT3 all had higher affinities for Cl-F-ara-A than for either Cl-dAdo or F-ara-A. Clofarabine 131-141 solute carrier family 29 member 2 Homo sapiens 84-89 16234483-8 2006 Affinity studies with recombinant transporters produced in yeast showed that hENT1, hENT2, and hCNT3 all had higher affinities for Cl-F-ara-A than for either Cl-dAdo or F-ara-A. Clofarabine 131-141 solute carrier family 28 member 3 Homo sapiens 95-100 16234483-4 2006 Cells producing hENT1 or hCNT3 exhibited the highest uptake of Cl-F-ara-A, whereas nucleoside transport-deficient cells and cells producing hCNT1 lacked uptake altogether. Clofarabine 63-73 solute carrier family 28 member 3 Homo sapiens 25-30 16234483-5 2006 When Cl-F-ara-A transport rates by hENT1 were compared with those of Cl-dAdo and F-ara-A, Cl-dAdo had the highest efficiency of transport, although Cl-F-ara-A showed the greatest accumulation during 5-min exposures. Clofarabine 5-15 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 35-40 16234483-6 2006 In cytotoxicity studies with the CEM lines, Cl-F-ara-A was more cytotoxic to cells producing hENT1 than to the nucleoside transport-deficient cells. Clofarabine 44-54 solute carrier family 29 member 1 (Augustine blood group) Homo sapiens 93-98 16234483-7 2006 The efficiency of Cl-F-ara-A transport by oocytes with recombinant transporters was hCNT3 > hENT2 > hENT1 > hCNT2; no transport was observed with hCNT1. Clofarabine 18-28 solute carrier family 28 member 3 Homo sapiens 84-89 15723262-2 2005 To investigate if clofarabine could be used with success in biochemical modulation strategies, we investigated the biochemical modulation of cytarabine triphosphate (ara-CTP) by clofarabine in a myeloid leukemia cell line and the effect of this combination on cytotoxicity. Clofarabine 178-189 solute carrier family 25 member 1 Homo sapiens 170-173 15803490-2 2005 In addition to inhibition of DNA polymerases and DNA synthesis, clofarabine acts as a strong inhibitor of ribonucleotide reductase (RnR), an enzyme involved in regulating intracellular deoxynucleotide pools, and has a high affinity to the enzyme deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside phosphorylation.A review of the English literature was performed that included original articles and related reviews from the MEDLINE (PubMed) data base and from abstracts based on the publication of meeting materials. Clofarabine 64-75 deoxycytidine kinase Homo sapiens 246-266 15803490-2 2005 In addition to inhibition of DNA polymerases and DNA synthesis, clofarabine acts as a strong inhibitor of ribonucleotide reductase (RnR), an enzyme involved in regulating intracellular deoxynucleotide pools, and has a high affinity to the enzyme deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside phosphorylation.A review of the English literature was performed that included original articles and related reviews from the MEDLINE (PubMed) data base and from abstracts based on the publication of meeting materials. Clofarabine 64-75 Cyd Drosophila melanogaster 268-272 15723262-6 2005 RESULTS: Clofarabine added either simultaneously or in sequence increased ara-CTP accumulation. Clofarabine 9-20 solute carrier family 25 member 1 Homo sapiens 78-81 15723262-7 2005 The maximal modulation of ara-CTP accumulation occurred with 1 microM clofarabine. Clofarabine 70-81 solute carrier family 25 member 1 Homo sapiens 30-33 15723262-9 2005 With 10 microM ara-C alone, 86 microM ara-CTP had accumulated after 3 h. The optimal sequence for the drug combination, i.e., clofarabine followed 4 h later by ara-C, resulted in 248 microM ara-CTP at 3 h. Clofarabine accumulated maximally in the monophosphate form. Clofarabine 126-137 solute carrier family 25 member 1 Homo sapiens 42-45 15723262-13 2005 CONCLUSIONS: These findings demonstrate that combination of clofarabine followed by ara-C results in a biochemical modulation of ara-CTP and synergistic cell kill. Clofarabine 60-71 solute carrier family 25 member 1 Homo sapiens 133-136 11071652-3 2000 In this study it is shown, by means of several assays on whole cells and isolated mitochondria, that 2-chloro-2"-deoxyadenosine (2CdA) and 2-choloro-2"-ara-fluorodeoxyadenosine (CaFdA) disrupt the integrity of mitochondria from primary chronic lymphocytic leukemia (B-CLL) cells. Clofarabine 178-183 cytidine deaminase Homo sapiens 130-133 12651272-2 2003 Although CAFdA is structurally similar to the clinically established analogs fludarabine and cladribine (CdA), its metabolism and mechanism of actions are significantly different. Clofarabine 9-14 cytidine deaminase Homo sapiens 105-108 12651272-6 2003 RESULTS: Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 microM and for CdA 0.15 microM, p<0.001). Clofarabine 43-48 cytidine deaminase Homo sapiens 149-152 12651272-6 2003 RESULTS: Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 microM and for CdA 0.15 microM, p<0.001). Clofarabine 43-48 cytidine deaminase Homo sapiens 149-152 12651272-6 2003 RESULTS: Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 microM and for CdA 0.15 microM, p<0.001). Clofarabine 133-138 cytidine deaminase Homo sapiens 53-56 12651272-6 2003 RESULTS: Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 microM and for CdA 0.15 microM, p<0.001). Clofarabine 133-138 cytidine deaminase Homo sapiens 53-56 12651272-7 2003 From the individual estimates the difference in cytotoxicity between CAFdA and CdA was more pronounced in cells from CLL patients (median EC50 for CAFdA 0.08 microM and for CdA 0.16 microM p<0.001) than in those from AML patients. Clofarabine 69-74 cytidine deaminase Homo sapiens 173-176 12651272-7 2003 From the individual estimates the difference in cytotoxicity between CAFdA and CdA was more pronounced in cells from CLL patients (median EC50 for CAFdA 0.08 microM and for CdA 0.16 microM p<0.001) than in those from AML patients. Clofarabine 147-152 cytidine deaminase Homo sapiens 79-82 12651272-10 2003 INTERPRETATION AND CONCLUSIONS: The greater in vitro cytotoxicity and cell metabolism of CAFdA compared to CdA confirm the high activity of CAFdA and encourage clinical trials with CAFdA in leukemic patients. Clofarabine 140-145 cytidine deaminase Homo sapiens 107-110 12651272-10 2003 INTERPRETATION AND CONCLUSIONS: The greater in vitro cytotoxicity and cell metabolism of CAFdA compared to CdA confirm the high activity of CAFdA and encourage clinical trials with CAFdA in leukemic patients. Clofarabine 140-145 cytidine deaminase Homo sapiens 107-110 12504799-0 2003 Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance. Clofarabine 97-108 deoxycytidine kinase Homo sapiens 19-39 12203101-6 2002 Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly in vivo. Clofarabine 36-45 BCL2 like 1 Homo sapiens 99-107 12203101-6 2002 Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly in vivo. Clofarabine 36-45 MCL1 apoptosis regulator, BCL2 family member Homo sapiens 112-117 12203101-6 2002 Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly in vivo. Clofarabine 36-45 AKT serine/threonine kinase 1 Homo sapiens 180-183 12203101-6 2002 Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly in vivo. Clofarabine 36-45 forkhead box O3 Homo sapiens 219-225 12203101-9 2002 Cl-F-araA induced a dose- and time-dependent downregulation of the Cdc25A protein whereas the Cdc25C protein remained unchanged. Clofarabine 0-9 cell division cycle 25A Homo sapiens 67-73 12504799-3 2003 The CdA and CAFdA resistant cell lines exhibited increased resistance to the other nucleoside analogues activated by dCK. Clofarabine 12-17 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 117-120 12504799-5 2003 The CdA and CAFdA resistant cells displayed a deficiency in dCK activity (to <5%) while the Fara-A resistant cells showed only a minor reduction of dCK activity (20% reduction). Clofarabine 12-17 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 60-63 12504799-8 2003 Expression of the recently identified RR subunit, p53R2 full-size protein, in CAFdA cells was low compared to parental cells, but a protein of lower molecular weight was detected in CdA and CAFdA cells. Clofarabine 78-83 ribonucleotide reductase regulatory TP53 inducible subunit M2B Homo sapiens 50-55 12504799-11 2003 We conclude that down-regulation of dCK in cells resistant to CdA and CAFdA and increased activity of RR in cells resistant to Fara-A contribute to resistance. Clofarabine 70-75 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 36-39 9463485-8 1998 This is the first report in which 2-fluoro-arabinosyl-adenine and 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine were shown to be good substrates for dGK. Clofarabine 66-110 Diacyl glycerol kinase Drosophila melanogaster 148-151 10499616-7 1999 The relative efficacy of CAFdA as a substrate for purified recombinant deoxycytidine kinase (dCK), the key enzyme in the activation of nucleoside analogues, was very high and exceeded that of CdA as well as the natural substrate, deoxycytidine, by a factor of 2 and 8, respectively. Clofarabine 25-30 deoxycytidine kinase Homo sapiens 71-91 10499616-7 1999 The relative efficacy of CAFdA as a substrate for purified recombinant deoxycytidine kinase (dCK), the key enzyme in the activation of nucleoside analogues, was very high and exceeded that of CdA as well as the natural substrate, deoxycytidine, by a factor of 2 and 8, respectively. Clofarabine 25-30 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 93-96 10499616-8 1999 The Km for CAFdA with dCK was also lower than that for CdA, as measured in crude extracts from the human acute lymphoblastic leukemia cell line CCRF-CEM and the promyelocytic leukemia cell line HL60. Clofarabine 11-16 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 22-25 10499616-9 1999 Acquired resistance to CAFdA in HL60 and in CCRF-CEM cell lines was directly correlated to the decreased activity of the nucleoside phosphorylating enzyme, dCK. Clofarabine 23-28 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 156-159 10499616-11 1999 These observations demonstrated that dCK phosphorylates CAFdA more efficiently than CdA. Clofarabine 56-61 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 37-40 9751270-0 1998 Analysis of DNA methylation of the 5" region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA)-resistant cells. Clofarabine 126-170 deoxycytidine kinase Homo sapiens 52-72 9751270-0 1998 Analysis of DNA methylation of the 5" region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA)-resistant cells. Clofarabine 172-177 deoxycytidine kinase Homo sapiens 52-72 9751270-2 1998 2-Chlorodeoxyadenosine (cladribine, CdA) and 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA) are purine nucleoside analogues which are also phosphorylated by dCK. Clofarabine 45-89 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 163-166 9751270-2 1998 2-Chlorodeoxyadenosine (cladribine, CdA) and 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA) are purine nucleoside analogues which are also phosphorylated by dCK. Clofarabine 91-96 Calcium/calmodulin-dependent protein kinase II Drosophila melanogaster 163-166 10606241-10 1999 The HL60/CdA cells showed cross-resistance to 2-chloro-2"-arabino-fluoro-2"-deoxyadenosine, Fara-A, arabinofuranosyl cytosine, difluorodeoxyguanosine, and difluorodeoxycytidine toxicity, most likely because of the decreased phosphorylation of these analogues by dCK. Clofarabine 46-90 cytidine deaminase Homo sapiens 9-12 9923554-1 1999 UNLABELLED: 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine (Cl-F-araA) is a novel deoxyadenosine analog, which inhibits DNA synthesis by inhibiting DNA polymerase alpha and ribonucleotide reductase. Clofarabine 12-73 DNA polymerase alpha 1, catalytic subunit Homo sapiens 163-183 9923554-1 1999 UNLABELLED: 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine (Cl-F-araA) is a novel deoxyadenosine analog, which inhibits DNA synthesis by inhibiting DNA polymerase alpha and ribonucleotide reductase. Clofarabine 75-84 DNA polymerase alpha 1, catalytic subunit Homo sapiens 163-183 7540950-2 1995 Studies with a variety of cell lines demonstrated that Cl-F-ara-A is a potent cytotoxic agent; in cell-free systems, its triphosphate (Cl-F-ara-ATP) inhibited DNA polymerase alpha and ribonucleotide reductase. Clofarabine 55-65 DNA polymerase alpha 1, catalytic subunit Homo sapiens 159-179 9215606-2 1997 2-Chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. Clofarabine 0-44 cytidine deaminase Homo sapiens 70-73 9215606-2 1997 2-Chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. Clofarabine 0-44 cytidine deaminase Homo sapiens 151-154 9215606-2 1997 2-Chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. Clofarabine 46-51 cytidine deaminase Homo sapiens 70-73 9215606-2 1997 2-Chloro-2"-arabino-fluoro-2"-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. Clofarabine 46-51 cytidine deaminase Homo sapiens 151-154