AT7519 is an ATP-competitive inhibitor of cyclin-dependent kinases (Cdks) with IC50 values of 210, 47, 100, 13, 170, and <10 nM for Cdk1, 2, 4, 5, 6, and 9, respectively. It is less potent against Cdk3 and Cdk7 and inactive against non-Cdk kinases save for GSK3β (IC50 = 89 nM). AT7519 demonstrates antiproliferative activity against a wide variety of human tumor cell lines (IC50s = 40-940 nM in vitro), inhibiting cell cycle progression and inducing apoptosis, and prevents tumor growth in human tumor xenograft models. AT7519 induces activation of GSK3β by down-regulating GSK3β phosphorylation, which contributes to AT7519-induced apoptosis.
