Target General Infomation
Target ID
T70176
Former ID
TTDC00088
Target Name
Cell division protein kinase 2
Gene Name
CDK2
Synonyms
Cyclin-dependent kinase 2; P33 protein kinase; SIN3-associated protein; Sin3 associated polypeptide; CDK2
Target Type
Clinical Trial
Disease Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B]
Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Non-small cell lung cancer [ICD10: C33-C34]
Psoriasis [ICD9: 696; ICD10: L40]
Retinoblastoma [ICD10: C69.2]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Small-cell lung cancer [ICD9: 162.9; ICD10: C33-C34]
Thymoma [ICD9: 164.0, 212.6; ICD10: C37, D15.0]
Function
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation ofDNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2(cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT- mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.
BioChemical Class
Kinase
Target Validation
T70176
UniProt ID
EC Number
EC 2.7.11.22
Sequence
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS
HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY
STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Drugs and Mode of Action
Drug(s) PHA848125 Drug Info Phase 2 Thymoma [522850], [542853]
R-roscovitine Drug Info Phase 2 Cancer [524796]
Ro 31-7453 Drug Info Phase 2 Solid tumours [531583]
Seliciclib Drug Info Phase 2 Non-small cell lung cancer [541292], [546752]
AG-024322 Drug Info Phase 1 Cancer [537564]
AZD-5438 Drug Info Phase 1 Solid tumours [530197], [543159]
PHA-793887 Drug Info Phase 1 Cancer [531377]
RGB-286638 Drug Info Phase 1 Hematological malignancies [523121], [542709]
SNS-032 Drug Info Phase 1 Solid tumours [537097], [541014]
TG02 Drug Info Phase 1 Cancer [531820]
INOC-005 Drug Info Preclinical Cancer [548139]
Capridine-beta Drug Info Discontinued in Phase 4 Psoriasis [533123]
SCH 727965 Drug Info Discontinued in Phase 3 Acute lymphoblastic leukemia [531565], [533028], [542400]
AT7519 Drug Info Discontinued in Phase 2 Solid tumours [530659], [530723], [541006]
BAY 10-00394 Drug Info Discontinued in Phase 2 Small-cell lung cancer [531973], [542800]
R547 Drug Info Discontinued in Phase 1 Advanced solid tumor [541047], [547737]
ZK 304709 Drug Info Discontinued in Phase 1 Advanced solid tumor [548143]
Olomoucine Drug Info Terminated Discovery agent [546498]
PD-0183812 Drug Info Terminated Retinoblastoma [547217]
Inhibitor (2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Fluoro-5'-methyl-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime Drug Info [530823]
(2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime Drug Info [530823]
1-Amino-6-Cyclohex-3-Enylmethyloxypurine Drug Info [551393]
2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Drug Info [528490]
2-Amino-6-Chloropyrazine Drug Info [551393]
2-ANILINO-6-CYCLOHEXYLMETHOXYPURINE Drug Info [551374]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Drug Info [528032]
3,4-diphenyl-1H-pyrrole-2,5-dione Drug Info [528032]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Drug Info [528490]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [528032]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [528032]
4-(2,4-Dimethyl-Thiazol-5-Yl)-Pyrimidin-2-Ylamine Drug Info [551393]
4-(7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol Drug Info [526504]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Drug Info [528490]
4-[(6-chloropyrazin-2-yl)amino]benzenesulfonamide Drug Info [551374]
4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline Drug Info [551391]
5-hydroxynaphthalene-1-sulfonamide Drug Info [551374]
5-nitroindirubin-3'-oxime Drug Info [530823]
6-(3-Amino-benzyloxy)-9H-purin-2-ylamine Drug Info [526389]
6-(3-Methyl-benzyloxy)-9H-purin-2-ylamine Drug Info [526389]
6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine Drug Info [526389]
6-CYCLOHEXYLMETHOXY-2-(3'-CHLOROANILINO) PURINE Drug Info [551374]
6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine Drug Info [526489]
6-CYCLOHEXYLMETHYLOXY-2-(4'-HYDROXYANILINO)PURINE Drug Info [551374]
6-O-Cyclohexylmethyl Guanine Drug Info [551393]
AG-024322 Drug Info [537564]
aloisine Drug Info [531779]
aloisine A Drug Info [526504]
Alsterpaullone Drug Info [535564]
Aminopurvalanol Drug Info [535564]
aminopurvalanol A Drug Info [529213]
AT7519 Drug Info [537034]
BAY 10-00394 Drug Info [550520]
Benzyl-(9-isopropyl-9H-purin-6-yl)-amine Drug Info [525825]
BMS-265246 Drug Info [531328]
BMS-536924 Drug Info [527711]
BOHEMINE Drug Info [525825]
BX-795 Drug Info [527484]
BX-912 Drug Info [527484]
Capridine-beta Drug Info [551434]
Cdk1/2 inhibitor III Drug Info [527600]
CDK2 inhibitors Drug Info [543528]
Cdk4 inhibitor III Drug Info [525734]
compound 3 Drug Info [529880]
compound 89S Drug Info [529892]
compound 9b Drug Info [529792]
CVT-313 Drug Info [543528]
Double Oxidized Cysteine Drug Info [551393]
GW-8510 Drug Info [526991]
Hymenialdisine Drug Info [535564]
Indirubin-3'-monoxime Drug Info [535564]
Indirubin-5-sulfonate Drug Info [535564]
INOC-005 Drug Info [530064]
JNJ-7706621 Drug Info [528188]
K00024 Drug Info [526625]
Lysine Nz-Carboxylic Acid Drug Info [551393]
MERIOLIN 1 Drug Info [529275]
MERIOLIN 2 Drug Info [529275]
MERIOLIN 3 Drug Info [529275]
MERIOLIN 4 Drug Info [529275]
MERIOLIN 5 Drug Info [529275]
MERIOLIN 6 Drug Info [529275]
MERIOLIN 8 Drug Info [529275]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE Drug Info [551374]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide Drug Info [528237]
N-(4-sulfamoylphenyl)-1H-indazole-3-carboxamide Drug Info [551374]
N-(5-Cyclopropyl-1h-Pyrazol-3-Yl)Benzamide Drug Info [551393]
N-phenyl-1H-pyrazole-3-carboxamide Drug Info [551374]
NSC-625987 Drug Info [525671]
NU-2058 Drug Info [528372]
NU-6027 Drug Info [526489]
NU-6086 Drug Info [530065]
NU-6094 Drug Info [530065]
NU-6102 Drug Info [528404]
NU6140 Drug Info [527749]
Olomoucine Drug Info [535564]
Oxindole 95 Drug Info [535564]
PD-0183812 Drug Info [525924]
PF-228 Drug Info [528764]
PHA-690509 Drug Info [531076]
PHA-793887 Drug Info [531377]
PHA848125 Drug Info [530259], [530591]
PHENYLAMINOIMIDAZO(1,2-ALPHA)PYRIDINE Drug Info [551374]
Purvalanol B Drug Info [535564]
PURVALANOLA Drug Info [529039]
PYRAZOLOPYRIDAZINE 1 Drug Info [527192]
PYRAZOLOPYRIDAZINE 2 Drug Info [527192]
R-roscovitine Drug Info [537564]
R547 Drug Info [537564]
RESCOVITINE Drug Info [530612]
RGB-286638 Drug Info [532412]
Ro 31-7453 Drug Info [536474]
SCH 727965 Drug Info [537564]
SCH-546909 Drug Info [543528]
Seliciclib Drug Info [536474], [537636]
SNS-032 Drug Info [537097], [537228]
SU9516 Drug Info [535564]
TRIAZOLOPYRIMIDINE Drug Info [551374]
VER-54505 Drug Info [543528]
ZK 304709 Drug Info [537564]
Modulator AZD-5438 Drug Info [530197]
TG02 Drug Info [531820]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway FoxO signaling pathway
Cell cycle
Oocyte meiosis
p53 signaling pathway
PI3K-Akt signaling pathway
Progesterone-mediated oocyte maturation
Hepatitis B
Measles
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Viral carcinogenesis
Prostate cancer
Small cell lung cancer
NetPath Pathway TCR Signaling Pathway
PANTHER Pathway p53 pathway
p53 pathway feedback loops 2
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Signaling events mediated by PRL
p73 transcription factor network
E2F transcription factor network
ATR signaling pathway
mTOR signaling pathway
IL2-mediated signaling events
FoxO family signaling
FOXM1 transcription factor network
BARD1 signaling events
p53 pathway
Regulation of retinoblastoma protein
Reactome G0 and Early G1
Activation of ATR in response to replication stress
Regulation of APC/C activators between G1/S and early anaphase
SCF(Skp2)-mediated degradation of p27/p21
Senescence-Associated Secretory Phenotype (SASP)
DNA Damage/Telomere Stress Induced Senescence
Processing of DNA double-strand break ends
G2 Phase
Orc1 removal from chromatin
Cyclin E associated events during G1/S transition
Cyclin A/B1 associated events during G2/M transition
p53-Dependent G1 DNA Damage Response
Cdk2-associated events at S phase entry
Meiotic recombination
Factors involved in megakaryocyte development and platelet production
WikiPathways DNA Damage Response
ID signaling pathway
DNA Replication
G1 to S cell cycle control
M/G1 Transition
S Phase
Meiotic Recombination
Aryl Hydrocarbon Receptor
ATM Signaling Pathway
Retinoblastoma (RB) in Cancer
Spinal Cord Injury
Integrated Pancreatic Cancer Pathway
Oncostatin M Signaling Pathway
Prostate Cancer
Signaling Pathways in Glioblastoma
TSH signaling pathway
Integrated Breast Cancer Pathway
Integrated Cancer pathway
Synthesis of DNA
Regulation of DNA replication
Mitotic G2-G2/M phases
Mitotic G1-G1/S phases
Factors involved in megakaryocyte development and platelet production
Cell Cycle
APC/C-mediated degradation of cell cycle proteins
Cell Cycle Checkpoints
miRNA Regulation of DNA Damage Response
References
Ref 522850ClinicalTrials.gov (NCT01011439) Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma. U.S. National Institutes of Health.
Ref 523121ClinicalTrials.gov (NCT01168882) Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies. U.S. National Institutes of Health.
Ref 524796ClinicalTrials.gov (NCT02160730) Treatment of Cushing's Disease With R-roscovitine. U.S. National Institutes of Health.
Ref 530197AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66.
Ref 530659AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36.
Ref 530723Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem. 2010 Mar 1;18(5):1844-53.
Ref 531377A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle. 2011 Mar 15;10(6):963-70. Epub 2011 Mar 15.
Ref 531565Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609. Epub 2011 Oct 1.
Ref 531583A phase 2 study of oral MKC-1, an inhibitor of importin-beta, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer. Invest New Drugs. 2012 Aug;30(4):1614-20.
Ref 531820Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
Ref 531973BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol Cancer Ther. 2012 Oct;11(10):2265-73.
Ref 533028Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443-8.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 537097Mechanism 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.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 541006(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5662).
Ref 541014(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5670).
Ref 541047(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5707).
Ref 541292(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6035).
Ref 542400(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7379).
Ref 542709(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7744).
Ref 542800(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7874).
Ref 542853(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7938).
Ref 543159(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8473).
Ref 546498Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008577)
Ref 546752Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010117)
Ref 547217Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014130)
Ref 547737Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018924)
Ref 548139Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022337)
Ref 548143Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022386)
Ref 525671The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. Clin Cancer Res. 1999 Dec;5(12):4279-86.
Ref 5257345-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cytotoxic agents. Bioorg Med Chem Lett. 2000 Mar 6;10(5):461-4.
Ref 525825J Med Chem. 2000 Jun 29;43(13):2506-13.Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2.
Ref 525924J Med Chem. 2000 Nov 30;43(24):4606-16.Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases.
Ref 526389J 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.
Ref 526489Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2.
Ref 526504J 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.
Ref 526625Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors. J Med Chem. 2003 May 22;46(11):2027-30.
Ref 526991Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles.
Ref 527192J 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.
Ref 527484Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74. Epub 2005 Mar 16.
Ref 5276001-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11.
Ref 527711J 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.
Ref 527749Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther. 2005 Sep;4(9):1328-37.
Ref 528032J Med Chem. 2006 Feb 23;49(4):1271-81.Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors.
Ref 528188Bioorg 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.
Ref 528237J 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.
Ref 528372J 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.
Ref 528404J Med Chem. 2006 Sep 7;49(18):5470-7.Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity.
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 528764J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28.Cellular characterization of a novel focal adhesion kinase inhibitor.
Ref 529039Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update.
Ref 529213Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
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 529792Bioorg Med Chem Lett. 2008 Dec 15;18(24):6486-9. Epub 2008 Oct 22.Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors.
Ref 5298802-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor. Bioorg Med Chem Lett. 2009 Feb 1;19(3):908-11.
Ref 529892First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem. 2009 Jan 22;52(2):293-307.
Ref 530064What are next generation innovative therapeutic targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15.
Ref 530065J Med Chem. 2009 May 14;52(9):2854-62.Halogen bonding--a novel interaction for rational drug design?.
Ref 530197AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66.
Ref 530259Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
Ref 530591The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound. Pharmacol Res. 2010 May;61(5):437-48.
Ref 530612Eur 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.
Ref 530823J 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.
Ref 531076Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6.
Ref 531328A robust high-content imaging approach for probing the mechanism of action and phenotypic outcomes of cell-cycle modulators. Mol Cancer Ther. 2011 Feb;10(2):242-54.
Ref 531377A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle. 2011 Mar 15;10(6):963-70. Epub 2011 Mar 15.
Ref 531779Identification of binding specificity-determining features in protein families. J Med Chem. 2012 Mar 8;55(5):1926-39.
Ref 531820Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
Ref 532412Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
Ref 535564Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
Ref 536474A 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.
Ref 537034Biological 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.
Ref 537097Mechanism 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.
Ref 537228Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 537636Cdk2 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).
Ref 543528(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1973).
Ref 550520National Cancer Institute Drug Dictionary (drug id 770319).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551391DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551434Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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