| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T85799 | ||||
| Target Name | Cell division protein kinase 4 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | ZK 304709 | Drug Info | IC50 = 61 nM | [537564] | |
| 1-(9-Oxo-9H-fluoren-4-yl)-3-pyridin-2-yl-urea | Drug Info | IC50 = 100 nM | [526223] | ||
| 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | IC50 = 13500 nM | [528490] | ||
| PYRAZOLOPYRIDAZINE 2 | Drug Info | Ki = 190 nM | [527192] | ||
| R547 | Drug Info | IC50 = 1~3 nM | [537564] | ||
| N-(2-(1H-Indol-3-yl)ethyl)biphenyl-4-carboxamide | Drug Info | IC50 = 16000 nM | [529613] | ||
| 10-hydroxy-18-methoxybetaenone | Drug Info | IC50 = 11500 nM | [525806] | ||
| AT7519 | Drug Info | IC50 < 100 nM | [537564] | ||
| PD-332991 | Drug Info | IC50 = 11 nM | [537564] | ||
| Flavopiridol | Drug Info | IC50 = 20~40 nM | [537564] | ||
| PYRAZOLOPYRIDAZINE 1 | Drug Info | Ki = 60 nM | [527192] | ||
| 1-Pyridin-2-yl-3-quinolin-5-yl-urea | Drug Info | IC50 = 2400 nM | [526223] | ||
| AG-024322 | Drug Info | IC50 = 1~3 nM | [537564] | ||
| 1-(1H-Indazol-6-yl)-3-pyridin-2-yl-urea | Drug Info | IC50 = 670 nM | [526223] | ||
| P276-00 | Drug Info | IC50 = 63 nM | [537564] | ||
| NU-6102 | Drug Info | IC50 = 1600 nM | [528404] | ||
| SNS-032 | Drug Info | IC50 = 925 nM | [537564] | ||
| 1-(7-Hydroxy-naphthalen-1-yl)-3-pyridin-2-yl-urea | Drug Info | IC50 = 7600 nM | [526223] | ||
| R-roscovitine | Drug Info | IC50 = 1~3 nM | [537564] | ||
| Action against Disease Model | R547 | Induced G1-G2 arrest and apoptosis in t uMour cell lines independently of RB1 or p53 status (IC50 < 0.60 mM); induced significant t uMour growth reduction in h uMan t uMour xenografts and efficacious with daily oral dosing and weekly intravenous dosing. Early clinical trials established tolerable dosage (155 mg per m2 infusion on day 1 and day 8 during a 21-day cycle), related toxicities (nausea, emesis and hypotension) and confirmed antit uMor activity. | [537564] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Mice expressing an endogenous Ink4-insensitive CDK4 R24C mutant develop a variety of t uMour types with complete penetrance | [537564] | |||
| References | |||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 526223 | J Med Chem. 2001 Dec 20;44(26):4615-27.Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. | ||||
| Ref 528490 | J 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 527192 | J 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 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 529613 | Bioorg Med Chem. 2008 Aug 15;16(16):7728-39. Epub 2008 Jul 8.Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4. | ||||
| Ref 525806 | J Nat Prod. 2000 Jun;63(6):739-45.Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species: novel inhibitors of protein kinases. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 527192 | J 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 526223 | J Med Chem. 2001 Dec 20;44(26):4615-27.Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 526223 | J Med Chem. 2001 Dec 20;44(26):4615-27.Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 528404 | J 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 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
| Ref 526223 | J Med Chem. 2001 Dec 20;44(26):4615-27.Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
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