| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T69991 | ||||
| Target Name | Wee1-like protein kinase | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | MK-1775 | Drug Info | IC50 = 5.2 nM | [537429] | |
| 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione | Drug Info | IC50 = 97 nM | [529785] | ||
| Action against Disease Model | MK-1775 | MK-1775. This compound inhibits phosphorylation of CDC2 at Tyr15 (CDC2Y15), a direct substrate of Wee1 kinase in cells. MK-1775 abrogates G(2) DNA damage checkpoint, leading to apoptosis in combination with DNA-damaging chemotherapeutic agents such as gemcitabine, carboplatin, and cisplatin selectively in p53-deficient cells. In vivo, MK-1775 potentiates t uMor growth inhibition by these agents, and cotreatment does not significantly increase toxicity. The enhancement of antit uMor effect by MK-1775 was well correlated with inhibition of CDC2Y15 phosphorylation in t uMortissue and skin hair follicles | [552997] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | WEE1 has a critical developmental role in mammals because WEE1-/- knockout mice embryos die before embryonic day 4 and conditionalWEE1 deletion results in growth defects and cell death due to DNA damage and chromosomal aneuploidy. | [537429] | |||
| References | |||||
| Ref 537429 | Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor. Mol Cancer. 2009 Jun 8;8:34. | ||||
| Ref 552997 | Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther. 2009 Nov;8(11):2992-3000. doi: 10.1158/1535-7163.MCT-09-0463. Epub 2009 Nov 3. | ||||
| Ref 529785 | Eur J Med Chem. 2009 Apr;44(4):1383-95. Epub 2008 Sep 30.Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. | ||||
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