837364-57-5
基本信息
AG-24322
AG-024322
AG024322
AG-024322
5-[3-(5,7-difluoro-1H-benzimidazol-2-yl)-1H-indazol-5-yl]-N-ethyl-4-methyl-3-Pyridinemethanamine
3-Pyridinemethanamine, 5-[3-(5,7-difluoro-1H-benzimidazol-2-yl)-1H-indazol-5-yl]-N-ethyl-4-methyl-
N-((5-((19E)-3-(4,6-DIFLUORO-2H-BENZO[D]IMIDAZOL-2-YLIDENE)-2,3-DIHYDRO-1H-INDAZOL-5-YL)-4-METHYLPYRIDIN-3-YL)METHYL)ETHANAMINE
物理化學(xué)性質(zhì)
常見問題列表
COX-1 2.3 nM (Ki) |
COX-2 3 nM (Ki) |
COX-4 2.9 nM (Ki) |
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 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.
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.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.
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. |