Therapeutic Targets Database
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TTD Target ID: TTDC00088

Target Information
NameCell division protein kinase 2    
Type of targetClinical trial target    
SynonymsCDK2    
Cyclin-dependent kinase 2    
P33 protein kinase    
SIN3-associated protein    
Sin3 associated polypeptide    
DiseaseAcute lymphoblastic leukemia (ALL)    [1][2][3]
Acute myeloid leukemia (AML)    [1][2][3]
Advanced Solid tumors    [4]
B-cell malignancies    [5][6][7]
Cancer, unspecific    [8]
Cardiovascular disease, unspecified    [9]
Chronic lymphocytic leukemia (CLL)    [1][2][3]
Hepatocellular Carcinoma (HCC)    [1][2][3]
Nasopharyngeal Cancer (NPC)    [10]
Non-Hodgkin's Lymphoma    [11]
Non-small Cell Lung Cancer    [10]
Solid tumors    [5][6][7]
Viral infection, unspecified    [8]
Drug(s)FlavopiridolPhase IIChronic lymphocytic leukemia[1][2][3]
FlavopiridolPhase IILymphoma[1][2][3]
Ro 31-7453Phase IIOvarian Cancer; Endometrial Cancer[12]
SCH 727965Phase IIAdvanced breast cancer, NSCLC, acute leukaemia and lymphoma[13]
AT7519Phase I/IINon-Hodgkin's Lymphoma[11]
R547Phase I completedNeoplasms, Advanced solid tumours[13]
AT7519Phase ISolid Tumors[11]
SCH 727965Phase IAdvanced solid tumours, NHL, multiple myeloma and CLL[13]
SNS-032Phase IB-lymphoid malignancies and advanced solid tumours[14][5]
SeliciclibPhase IAdvanced Solid Tumors[12][15]
ZK 304709Phase IAdvanced solid tumours[13]
AG-024322Terminated in Phase IAdvanced cancer[13]
FlavopiridolDiscontinuedHepatocellular Carcinoma[1][2][3]
R-roscovitineTerminated in Phase IINon-Small Cell Lung Cancer (NSCLC)[13]
SeliciclibTerminated in Phase IIBreast, NSCLC, lymphoid leukemia, glomerulonephritis & multiple myeloma[12][15]
Capridine-betaPreclinicalAdvanced Solid Tumors[16]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.-
EC 2.7.1.37
PathwayCell cycle
Pathways in cancer
Prostate cancer
Small cell lung cancer
p53 signaling pathway
UniProt IDP24941
PDB Structure1AQ1; 1B38; 1B39; 1BUH; 1CKP; 1DI8; 1DM2; 1E1V.    
FunctionProbably involved in the control of the cell cycle. Interacts with cyclins a, d, or e. Activity of cdk2 is maximal during s phase and g2.    
SequenceMENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Related US Patent6,387,919
6,465,507
6,541,503
6,635,640
Target ValidationClick to Find Target Validation Information.    
Inhibitor (2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Fluoro-5'-methyl-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime[17]
(2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime[17]
1-Amino-6-Cyclohex-3-Enylmethyloxypurine[18]
2- ([19]
2-ANILINO-6-CYCLOHEXYLMETHOXYPURINE[20]
2-Amino-6-Chloropyrazine[18]
3,4-di- (4-methoxyphenyl)-1H-pyrrole-2,5-dione[21]
3,4-diphenyl-1H-pyrrole-2,5-dione[21]
3- ([19]
3- (4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione[21]
3- (indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione[21]
4- (2,4-Dimethyl-Thiazol-5-Yl)-Pyrimidin-2-Ylamine[18]
4- (7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol[22]
4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol[19]
4-[ (6-chloropyrazin-2-yl)amino]benzenesulfonamide[20]
4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline[23]
5-hydroxynaphthalene-1-sulfonamide[20]
5-nitroindirubin-3'-oxime[17]
6- (3-Amino-benzyloxy)-9H-purin-2-ylamine[24]
6- (3-Methyl-benzyloxy)-9H-purin-2-ylamine[24]
6- (Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine[24]
6-CYCLOHEXYLMETHOXY-2- (3'-CHLOROANILINO) PURINE[20]
6-CYCLOHEXYLMETHYLOXY-2- (4'-HYDROXYANILINO)PURINE[20]
6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine[25]
6-O-Cyclohexylmethyl Guanine[18]
AG-024322[13]
AT7519[11]
AZD-0530[26]
Alsterpaullone[8]
Aminopurvalanol[8]
BMS-536924[27]
BOHEMINE[28]
Benzyl- (9-isopropyl-9H-purin-6-yl)-amine[28]
Capridine-beta[16]
Double Oxidized Cysteine[18]
Flavopiridol[29]
Flavopiridol[1][2][3]
GW-8510[30]
Hymenialdisine[31]
Hymenialdisine[8]
Indirubin-3'-Monoxime[31]
Indirubin-3'-monoxime[8]
Indirubin-5-sulfonate[8]
JNJ-7706621[32]
Lysine Nz-Carboxylic Acid[18]
MERIOLIN 1[33]
MERIOLIN 2[33]
MERIOLIN 3[33]
MERIOLIN 4[33]
MERIOLIN 5[33]
MERIOLIN 6[33]
MERIOLIN 8[33]
N- (3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE[20]
N- (4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide[34]
N- (4-sulfamoylphenyl)-1H-indazole-3-carboxamide[20]
N- (5-Cyclopropyl-1h-Pyrazol-3-Yl)Benzamide[18]
N-phenyl-1H-pyrazole-3-carboxamide[20]
NU-2058[35]
NU-6027[35]
NU-6027[25]
NU-6086[36]
NU-6094[36]
NU-6102[37]
OLOMOUCINE II[20]
Olomoucine[18]
Olomoucine[8]
Oxindole 95[8]
PD-0183812[38]
PF-228[39]
PHENYLAMINOIMIDAZO (1,2-ALPHA)PYRIDINE[20]
PURVALANOLA[40]
PYRAZOLOPYRIDAZINE 1[41]
PYRAZOLOPYRIDAZINE 2[41]
Purvalanol[18]
Purvalanol B[8]
R-roscovitine[13]
R547[13]
RESCOVITINE[42]
Ro 31-7453[12]
Roscovitine[43]
SB-216763[44]
SCH 727965[13]
SNS-032[14][5]
SU9516[31]
SU9516[8]
Seliciclib[12][15]
Staurosporine[18]
TRIAZOLOPYRIMIDINE[20]
ZK 304709[13]
MultitargetAG-024322[13]
Capridine-beta[16]
R-roscovitine[13]
R547[13]
Ro 31-7453[12]
SCH 727965[13]
SNS-032[14][5]
ZK 304709[13]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Flavopiridol reduces the impedance of neural prostheses in vivo without affecting recording quality. J Neurosci Methods. 2009 Jun 26. [Epub ahead of print] To Reference
Ref 2The effect of the cyclin-dependent kinase inhibitor flavopiridol on anaplastic large cell lymphoma cells and relationship with NPM-ALK kinase expression and activity. Haematologica. 2009 Jul;94(7):944-55. Epub 2009 Jun 16. To Reference
Ref 3A phase II study of flavopiridol (Alvocidib) in combination with docetaxel in refractory, metastatic pancreatic cancer. Pancreatology. 2009;9(4):404-9. Epub 2009 May 19. To Reference
Ref 4Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype. Clin Immunol. 2009 Apr;131(1):98-108. Epub 2009 Jan 12. To Reference
Ref 5Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43. To Reference
Ref 6SNS-032 prevents hypoxia-mediated glioblastoma cell invasion by inhibiting hypoxia inducible factor-1alpha expression. Int J Oncol. 2009 Apr;34(4):1051-60. To Reference
Ref 7SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. Neoplasia. 2007 May;9(5):370-81. To Reference
Ref 8Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25. To Reference
Ref 9Nebivolol inhibits human aortic smooth muscle cell growth: effects on cell cycle regulatory proteins. J Cardiovasc Pharmacol. 2000 Jun;35(6):845-8. To Reference
Ref 10Therapeutic efficacy of seliciclib in combination with ionizing radiation for human nasopharyngeal carcinoma. Clin Cancer Res. 2009 Jun 1;15(11):3716-24. Epub 2009 May 26. To Reference
Ref 11Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32. Epub 2009 Jan 27. To Reference
Ref 12A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference
Ref 13Nat Rev Drug Discov. 2009 Jul;8(7):547-66.Cell cycle kinases as therapeutic targets for cancer. To Reference
Ref 14Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. Epub 2009 Feb 20. To Reference
Ref 15Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo. Cell Cycle. 2009 Sep 8;8(17). [Epub ahead of print] To Reference
Ref 16Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc.. 2005 To Reference
Ref 17J Med Chem. 2010 May 13;53(9):3696-706.5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. To Reference
Ref 18Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 19J 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. To Reference
Ref 20Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 21J Med Chem. 2006 Feb 23;49(4):1271-81.Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. To Reference
Ref 22J Med Chem. 2003 Jan 16;46(2):222-36.Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. To Reference
Ref 23Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 24J Med Chem. 2002 Aug 1;45(16):3381-93.Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. To Reference
Ref 25Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. To Reference
Ref 26J Med Chem. 2006 Nov 2;49(22):6465-88.N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. To Reference
Ref 27J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. To Reference
Ref 28J Med Chem. 2000 Jun 29;43(13):2506-13.Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2. To Reference
Ref 29Zvelebil MJ: Flavopiridol (Hoechst AG). IDrugs. 1998 Jun;1(2):241-6. To Reference
Ref 30Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. To Reference
Ref 31Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. To Reference
Ref 32Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. Epub 2006 May 6.Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. To Reference
Ref 33J 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/meriolin complex. To Reference
Ref 34J Med Chem. 2006 Jun 15;49(12):3563-80.Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. To Reference
Ref 35J Med Chem. 2006 Aug 24;49(17):5141-53.Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. To Reference
Ref 36J Med Chem. 2009 May 14;52(9):2854-62.Halogen bonding--a novel interaction for rational drug design? To Reference
Ref 37J Med Chem. 2006 Sep 7;49(18):5470-7.Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. To Reference
Ref 38J Med Chem. 2000 Nov 30;43(24):4606-16.Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. To Reference
Ref 39J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28.Cellular characterization of a novel focal adhesion kinase inhibitor. To Reference
Ref 40Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 41J Med Chem. 2004 Sep 9;47(19):4716-30.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 efficacy. To Reference
Ref 42Eur J Med Chem. 2010 Mar;45(3):1158-66. Epub 2009 Dec 21.Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. To Reference
Ref 43Inhibition of CDKs by roscovitine suppressed LPS-induced *NO production through inhibiting NF{kappa}B activation and BH4 biosynthesis in macrophages. Am J Physiol Cell Physiol. 2009 Jun 24. [Epub ahead of print] To Reference
Ref 44J Med Chem. 2010 Feb 11;53(3):994-1003.Benzo[e]isoindole-1,3-diones as potential inhibitors of glycogen synthase kinase-3 (GSK-3). Synthesis, kinase inhibitory activity, zebrafish phenotype, and modeling of binding mode. To Reference



 

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