CVT 313

CVT-313 (Cdk2 Inhibitor III) has been shown to inhibit other kinases, but at much higher IC ₅₀ values, i.e., CDK1 (IC ₅₀ =4.2 μM), CDK4 D1 (IC ₅₀ =215 μM), and MAPK/PKA/PKC (IC ₅₀ >1.25 mM), compared to CDK2 (IC ₅₀ =0.5 μM). CVT-313 has been shown to have profound effects on cell proliferation at concentrations of 5-20 μM. CVT-313 is a potent CDK2 inhibitor, which is identified from a purine analog library with an IC ₅₀ of 0.5 μM in vitro. Inhibition is competitive with respect to ATP (K _i =95 nM), and selective CVT-313 has no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 is required for half-maximal inhibition of the enzyme activity. Using normal and tumor human/murine cell lines, the effects of CVT-313 on cell proliferation is measured. The IC ₅₀ for growth inhibition ranged from 1.25 to 20 μM.