Description
AT7519 is an ATP-competitive inhibitor of cyclin-dependent kinases (Cdks) with IC
50 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 (IC
50 = 89 nM). AT7519 demonstrates antiproliferative activity against a wide variety of human tumor cell lines (IC
50s = 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.
IC 50
CDK9/Cyclin T: 10 nM (IC
50); CDK5/p35: 13 nM (IC
50); cdk2/cyclin A: 47 nM (IC
50); Cdk4/cyclin D1: 100 nM (IC
50); cdk6/cyclin D3: 170 nM (IC
50); Cdk1/cyclin B: 210 nM (IC
50); CDK7/Cyclin H/MAT1: 2400 nM (IC
50); GSK3β: 89 nM (IC
50)
