Adavosertib

Adavosertib (AZD-1775; MK-1775) is a potent Wee1 inhibitor with an IC₅₀ of 5.2 nM. IC50 & Target: IC50: 5.2 nM (Wee1) In Vitro: Adavosertib (MK-1775) enhances the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. Adavosertib (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^[1]. Adavosertib (MK-1775) abrogates the radiation-induced G2 block in p53-defective cells but not in p53 wild-type lines^[2]. The combination of NSC 613327 with Adavosertib (MK-1775) produces robust anti-tumor activity and remarkably enhances tumor regression response (4.01 fold) compared to NSC 613327 treatment in p53-deficient tumors^[3]. In Vivo: In vivo, Adavosertib (MK-1775) potentiates the anti-tumor efficacy of 5-FU at tolerable doses^[1]. Adavosertib (MK-1775) (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionated radiotherapy^[2]. Adavosertib (MK-1775) (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice^[3].