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Country: China (Mainland)
Business Type:Lab/Research institutions
MK-1775 is a potent Wee1 inhibitor with IC50 of 5.2 nM. IC50 & Target: IC50: 5.2 nM (Wee1) In Vitro: MK-1775 enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. MK-1775 inhibits CDC2 Y15 phosphorylation in cells, abrogates DNA damaged checkpoints induced by 5-FU treatment, and causes premature entry of mitosis determined by induction of Histone H3 phosphorylation. MK-1775 abrogates the radiation-induced G2 block in p53-defective cells but not in p53 wild-type lines. The combination of gemcitabine with MK-1775 produces robust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to gemcitabine treatment in p53-deficient tumors. In Vivo: In vivo, MK-1775 potentiates the anti-tumor efficacy of 5-FU or its prodrug, capecitabine, at tolerable doses. MK-1775 (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionated radiotherapy. MK-1775 (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice