Target Validation Information
TTD ID T70176
Target Name Cyclin-dependent kinase 2 (CDK2)
Type of Target
Clinical trial
Drug Potency against Target AT7519 Drug Info IC50 = 10 nM [21]
Flavopiridol Drug Info IC50 = 60 nM [22]
R-roscovitine Drug Info IC50 = 200 nM [20]
R-roscovitine Drug Info Ki = 100 nM [24]
R547 Drug Info IC50 = 1~3 nM [18]
SCH 727965 Drug Info Ki = 1 nM [23]
SNS-032 Drug Info Ki = 38 nM
ZK 304709 Drug Info Ki = 4 nM [19]
AG-024322 Drug Info IC50 = 1~3 nM [18]
(2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime Drug Info IC50 = 4120 nM [17]
(2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime Drug Info IC50 = 2950 nM [17]
2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Drug Info IC50 = 2500 nM [12]
2-ANILINO-6-CYCLOHEXYLMETHOXYPURINE Drug Info IC50 = 2300 nM [15]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Drug Info IC50 = 6000 nM [12]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Drug Info IC50 = 3500 nM [12]
5-nitroindirubin-3'-oxime Drug Info IC50 = 7.35 nM [17]
6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine Drug Info IC50 = 13000 nM [3]
6-cyclohexylmethyloxy-2-(4'-hydroxyanilino)purine Drug Info IC50 = 1000 nM [15]
6-O-Cyclohexylmethyl Guanine Drug Info Ki = 1200 nM [10]
aloisine A Drug Info IC50 = 400 nM [5]
Benzyl-(9-isopropyl-9H-purin-6-yl)-amine Drug Info IC50 = 4500 nM [1]
BOHEMINE Drug Info IC50 = 800 nM [1]
GW-8510 Drug Info IC50 = 10 nM [6]
JNJ-7706621 Drug Info IC50 = 2 nM [8]
MERIOLIN 1 Drug Info IC50 = 90 nM [14]
MERIOLIN 2 Drug Info IC50 = 18 nM [14]
MERIOLIN 3 Drug Info IC50 = 11 nM [14]
MERIOLIN 4 Drug Info IC50 = 7 nM [14]
MERIOLIN 5 Drug Info IC50 = 3 nM [14]
MERIOLIN 6 Drug Info IC50 = 5.1 nM [14]
MERIOLIN 8 Drug Info IC50 = 1800 nM [14]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide Drug Info Ki = 1300 nM [9]
NU-6027 Drug Info IC50 = 2200 nM [4]
NU-6102 Drug Info IC50 = 8.1 nM [11]
PD-0183812 Drug Info IC50 = 165 nM [2]
Purvalanol A Drug Info IC50 = 30 nM [13]
PYRAZOLOPYRIDAZINE 1 Drug Info Ki = 2 nM [7]
PYRAZOLOPYRIDAZINE 2 Drug Info Ki = 50 nM [7]
RESCOVITINE Drug Info IC50 = 500 nM [16]
Action against Disease Model Flavopiridol Drug Info Induced G1-S phase and G2-M phase arrest and apoptosis at 200-300 nM concentrations in many tumor cell types. Significant clinical activity in refractory CLL; clinical studies ongoing to determine efficacy of combination with anti-neoplastic agents. [18]
References
REF 1 Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2. J Med Chem. 2000 Jun 29;43(13):2506-13.
REF 2 Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
REF 3 Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. J Med Chem. 2002 Aug 1;45(16):3381-93.
REF 4 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.
REF 5 Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.
REF 6 Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.
REF 7 N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular effi... J Med Chem. 2004 Sep 9;47(19):4716-30.
REF 8 Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41.
REF 9 Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem. 2006 Jun 15;49(12):3563-80.
REF 10 Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J Med Chem. 2006 Aug 24;49(17):5141-53.
REF 11 Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem. 2006 Sep 7;49(18):5470-7.
REF 12 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
REF 13 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
REF 14 Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin com... J Med Chem. 2008 Feb 28;51(4):737-51.
REF 15 Halogen bonding--a novel interaction for rational drug design J Med Chem. 2009 May 14;52(9):2854-62.
REF 16 Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. Eur J Med Chem. 2010 Mar;45(3):1158-66.
REF 17 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010 May 13;53(9):3696-706.
REF 18 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
REF 19 Molecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709. Biomed Pharmacother. 2006 Jul;60(6):269-72.
REF 20 A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32.
REF 21 Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds. Nat Rev Drug Discov. 2009 Jul;8(7):567-78.
REF 22 End of the line for cannabinoid receptor 1 as an anti-obesity target An opinion. Nat Rev Drug Discov. 2009 Jul;8(7):594.
REF 23 Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53.
REF 24 A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem. 2010 Dec 23;53(24):8508-22.

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