AZD-5438

A potent and oral inhibitor of CDK1/2/9 with IC50 of 16/6/20 nM, respectively; also inhibits the kinase activity of p25-Cdk5 (IC50=14 nM) and GSK-3β (IC50=17 nM) in vitro, displays 75-fold less active against cyclin D-Cdk4; shows significant antiproliferative activity in human tumor cell lines (IC50 range: 0.2-1.7 uM), inhibits the phosphorylation of Cdk substrates pRb, nucleolin, PP1A, and RNA polymerase II COOH-terminal domain and blocks cell cycle; inhibits the human tumor xenograft growth in vivo; also inhibits PASTA kinase in L. monocytogenes (PrkA) and L. monocytogenes growth in a β-lactam-synergism-dependent manner.Solid Tumors Phase 1 Discontinued.