844442-38-2|AT7519 is a novel small molecule effective as a multi-cyclin-dependent kinase inhibitor for Cdk1/cyclin B (IC50 = 210 nM), Cdk2/Cyclin A (IC50 = 47 nM), Cdk3/Cyclin E (IC50 = 360 nM), Cdk4/Cyclin D1 (IC50 = 100 nM), Cdk5/p35 (IC50 = 13 nM) and Cdk6/Cyclin D3 (IC50 = 170 nM). AT7519 is an ATP competitive Cdk inhibitor with a Ki value of 38 nM for Cdk1. AT7519 is inactive against all non-Cdk kinases with the exception of GSK3β (IC50 = 89 nM). AT7519 shows potent antiproliferative activity in a variety of human tumor cell lines with IC50 values ranging from 40 nM for MCF-7 to 940 nM for SW620. AT7519 induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to AT7519 induced apoptosis independent of the inhibition of transcription.
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