Cdk4/6 inhibitor IV is a cell-permeable triaminopyrimidine that reversibly blocks Cdk4/cyclin D1 and Cdk6/cyclin D1 activity with IC50 values of 1.5 and 5.6 μM, respectively. It demonstrates potent selectivity for Cdk4/6 over Cdk5/p35, v-abl, c-met, IGF-1R, insulin receptor, Cdk2/cyclin A, Cdk2/cyclin E, Cdk4/cyclin D2, Cdk6/cyclin D2, and Cdk1/cyclin B (IC50s = > 10-100 μM). At 5-10 μM, this compound blocks retinoblastoma protein phosphorylation at Ser780 and Ser795, inducing cell cycle arrest in the G1 phase and apoptosis in asynchronous cell lines. In mice bearing human HCT116 colon carcinoma xenografts, 30 mg/kg, i.p. Cdk/6 inhibitor IV suppressed tumor growth after 29 days of treatment.
