MK-1775

MK-1775

【产品别名】AZD-1775; AZD1775; AZD 1775

【CAS号】 955365-80-7

【目录编号】 2H-38

【纯度】 99.89%

【分子式】 C27H32N8O2

【分子量】 500.6

【简介】 MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM; hinders G2 DNA damage checkpoint.

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MK-1775 详细介绍

MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM; hinders G2 DNA damage checkpoint.
IC50 Value: 5.2 nM
Target: Wee1
in vitro: MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells.
in vivo: MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models models is also moderate.

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