Adavosertib

A potent and selective small-molecule inhibitor of Wee1 kinase with IC50 of 5.2 nM; exhibits ATP-competitive and highly selective against other serine/threonine or tyrosine kinases; inhibits phosphorylation of CDC2 at Tyr15 in cells; potentiates tumor growth inhibition in vivo.Lung Cancer Phase 2 Clinical (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. Adavosertib (MK-1775) abrogates the radiation-induced G2 block in p53-defective cells but not in p53 wild-type lines. 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. (In Vivo) :In vivo, Adavosertib (MK-1775) potentiates the anti-tumor efficacy of 5-FU at tolerable doses. Adavosertib (MK-1775) (60 mg/kg twice daily, p.o.) enhances H1299 xenograft tumor response to fractionated radiotherapy. Adavosertib (MK-1775) (30 mg/kg. p.o.) regresses tumor growth in PANC198, PANC215 and PANC185 as compared to GEM treated mice.

955365-80-7

AZD-1775 | MK-1775

>98% (HPLC)

10 mM in DMSO

O=C1N (CC=C) N (C2=NC (C (C) (O) C) =CC=C2) C3=NC (NC4=CC=C (N5CCN (C) CC5) C=C4) =NC=C31

C27H32N8O2

500.5954

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.