Target Validation Information
TTD ID T69991
Target Name Wee1-like protein kinase (WEE1)
Type of Target
Clinical trial
Drug Potency against Target MK-1775 Drug Info IC50 = 5.2 nM [2]
9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Drug Info IC50 = 97 nM [1]
Action against Disease Model MK-1775 Drug Info 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 [3]
References
REF 1 Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. Eur J Med Chem. 2009 Apr;44(4):1383-95.
REF 2 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 3 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.

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