AZ20

AZ20 is a potent and selective inhibitor of ATR with an IC₅₀ of 5 nM, and has 8-fold selectivity against mTOR (IC₅₀=38 nM). IC50 & Target: IC50: 5 nM (ATR), 38 nM (mTOR)^[1] In Vitro: AZ20 inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC₅₀ of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC₅₀ of 50 nM^[1]. In Vivo: AZ20 (25, 50 mg/kg, p.o.) has high permeability combined with good stability to rat hepatocytes and, despite the lack of progress in achieving markedly higher solubility, has respectable bioavailability in a low dose rat PK study. AZ20 (25, 50 mg/kg, p.o.) leads to significant tumor growth inhibition in female nude mice bearing LoVo tumors^[1].