AG-024322

AG-024322 is a potent ATP-competitive pan-CDK inhibitor against cell cycle kinases CDK1, CDK2, and CDK4 with K_i values in the 1-3 nM range^[1]. AG-024322 displays broad-spectrum anti-tumor activity and clear target modulation in vivo. AG-024322 induces cell apoptosis^[3]. In Vitro: AG-024322 (0.1-30 μM; 24 hours) is less toxic at concentrations below 3 µM, the viability of human PBMCs as measured by ATP content with a TC₅₀ value of 1.4 µM for human PBMCs^[2].
AG-024322 (0-120 nM) exhibits growth inhibition effects on HCT-116 cells. It is slightly less potent in the functional cellular assay with an IC₅₀ of 120 nM^[2].
In Vivo: AG-024322 (intravenous infusion; 2, 6, and 10 mg/kg; 5 days) exhibits no-adverse-effect at 2 mg/kg with mean plasma AUC (0-24.5) of 2.11 g.h/mL. At 6 mg/kg produces pancytic bone marrow hypocellularity, lymphoid depletion. And vascular injury at the injection site renal tubular degeneration occurs at 10 mg/kg^[1].
AG-024322 (20 mg/kg) inhibits the growth of established human tumor xenografts of different origins with tumor growth inhibition (TGI) ranging from 32% to 86.4%.It also exhibits anti-tumor effects as a dose-pdependent manner^[3].
AG-024322 (20 mg/kg) causes a 65% TGI in the MV522 tumor model. It results a 52% TGI at 1/2 of the maximum tolerated dose (MTD) and only slight anti-tumor activity at 1/4 of the MTD^[3].