AG-024322 (C09-1102-877)

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 AG-024322 displays broad-spectrum anti-tumor activity and clear target modulation in vivo. AG-024322 induces cell apoptosisIn VitroAG-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 TC 50 value of 1.4 µM for human PBMCs. 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 IC 50 of 120 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoAG-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 . 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. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male and female cynomolgus monkeys Dosage: 2, 6, and 10 mg/kg (Toxicity analysis) Administration: Intravenous infusion; 5 days Result: Resulted in dose-dependent pancytic bone marrow hypocellularity and lymphoid depletion in lymph nodes, spleen, and/or thymus at >6 mg/kg.Form:SolidIC50& Target:COX-1 2.3 nM (Ki) COX-2 3 nM (Ki) COX-4 2.9 nM (Ki). Specifications and Purity: 98%. Molecular Formula: C23H20F2N6. Molecular Weight: 418.44. PubChem CID: 135413565. Isomeric SMILES: CCNCC1=CN=CC(=C1C)C2=CC3=C(C=C2)NN=C3C4=NC5=C(N4)C=C(C=C5F)F.