Target Validation Information
Target ID T44458
Target Name Cell division protein kinase 9
Target Type
Clinical Trial
Drug Potency against Target AT7519 Drug Info IC50 < 10 nM [537564]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Drug Info IC50 = 1500 nM [528490]
P276-00 Drug Info IC50 = 20 nM [537564]
MERIOLIN 7 Drug Info IC50 = 5300 nM [529275]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Drug Info IC50 = 350 nM [528490]
SCH 727965 Drug Info Ki = 4 nM [553063]
R-roscovitine Drug Info IC50 = 230 nM [537564]
SNS-032 Drug Info IC50 = 1 nM [552961]
MERIOLIN 2 Drug Info IC50 = 18 nM [529275]
MERIOLIN 6 Drug Info IC50 = 5.6 nM [529275]
MERIOLIN 4 Drug Info IC50 = 7 nM [529275]
MERIOLIN 1 Drug Info IC50 = 26 nM [529275]
MERIOLIN 8 Drug Info IC50 = 1200 nM [529275]
Flavopiridol Drug Info IC50 = 3 nM [537564]
4-(phenyldiazenyl)-1H-pyrazole-3,5-diamine Drug Info IC50 = 15000 nM [528490]
ZK 304709 Drug Info IC50 = 4 nM [552961]
MERIOLIN 3 Drug Info IC50 = 6 nM [529275]
MERIOLIN 5 Drug Info IC50 = 5.6 nM [529275]
Action against Disease Model SCH 727965 Induced apoptosis in t uMour cell lines and growth inhibition or regression in xenograft models. [537564] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations (A) TBP is specifically enriched at the TSS and is not affected by CDK9 knockdown, whereas CDK9 is significantly enriched both at the TSS and at 0.5 kb and these levels decreaseon knockdown. (B) CDK9 knockdown similarly decreases RNAPII and P-Ser 5-RNAPII levels at the TSS without affecting elongation to the 3'-end cleavage site. By contrast, P-Ser 2 is markedly decreased to near-background levels both at the TSS and at 0.5 kb. (C) The H2B-ubiquitinating complex (PAF1, RNF20 and RNF40) is enriched at 0.5 kb of the HIST1H2BD gene together with H2Bub1, and their levels decrease following CDK9 knockdown. (D) ChIP analysis of SLBP and the U7 snRNP component LSM11 shows decreased recruitment to the 3'-cleavage site. (E) CDK9 knockdown increases RNAPII read-through past the normal 3'-end cleavage site of the HIST1H2BD and HIST1H2AC genes. [537564]
References
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 528490J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 528490J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects.
Ref 553063Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 552961End of the line for cannabinoid receptor 1 as an anti-obesity target? An opinion. Nat Rev Drug Discov. 2009 Jul;8(7):594. doi: 10.1038/nrd2775-c1.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 528490J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects.
Ref 552961End of the line for cannabinoid receptor 1 as an anti-obesity target? An opinion. Nat Rev Drug Discov. 2009 Jul;8(7):594. doi: 10.1038/nrd2775-c1.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.
Ref 529275J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex.

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