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Biological Activity:
A potent and selective Wee1 kinase inhibitor in vitro and in vivo.
MK 1775 abolishes cyclin-dependent kinase 1 (CDC2) activity by phosphorylation of the Tyr15 residue. It abrogates a DNA damage checkpoint (G2-phase), leading to apoptosis in combination with several DNA-damaging agents selectively in p53-deficient tumor cell lines. It is under clinical trial for advanced solid tumors.
References:
H. Hirai et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol. Cancer. Ther. 2009, 8(11), 2992-3000. [online]
S. Schellens et al. A Phase I and pharmacological study of MK-1775, a Wee1 tyrosine kinase inhibitor, in both monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors. J. Clin. Oncol. 2009, 27(15s), abstr 3510.
H. Hirai et al. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol. Ther. 2010, 9(7), 523-525. [online]
Chemical Name: 1,2-dihydro-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-2-(2-propen-1-yl)-3H-Pyrazolo[3,4-d]pyrimidin-3-one
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