Dinaciclib (SCH727965) is a novel and potent cyclin-dependent kinase inhibitor for Cdk2 (IC50 = 1 nM), Cdk5 (IC50 = 1 nM), Cdk1 (IC50 = 3 nM), and Cdk9 (IC50 = 4 nM). Dinaciclib is also a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells (IC50 = 4 nM). Dinaciclib strongly suppresses phosphorylation of Rb on Ser807/811 at concentrations >6.25 nM. Significantly, complete suppression of Rb phosphorylation is correlated with the onset of apoptosis, as indicated by the appearance of the p85 PARP cleavage product in cells exposed to >6.25 nM Dinaciclib. Dinaciclib is active against a broad spectrum of human tumor cell lines.
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