| Description | AS-2444697 is an inhibitor of IRAK-4 (C50 = 21 nM). AS-2444697 exhibits renoprotective effects through anti-inflammatory action. AS-2444697 potently inhibits human and rat IRAK-4 activity. |
| In vitro | AS-2444697 (0.3-3 mg/kg) 在LPS/GalN处理的小鼠中显著增加了IL-1β、IL-6、TNF-α、MCP-1以及氨基转移酶（ALT和AST）的血浆水平。单次给药AS-2444697（0.3-3 mg/kg）呈剂量依赖性降低了这些参数的血浆水平，且在1 mg/kg或更高剂量时效果显著[1]。口服AS-2444697（3 mg/kg）给5/6 Nx大鼠后，未改变化合物在血浆和组织（肝脏和肾脏）中的浓度在1小时达到峰值，然后逐渐降低，终末半衰期为2.7-2.9小时[1]。AS-2444697在大鼠佐剂诱导的关节炎（ED50 2.7 mg/kg，BID，PO）和大鼠胶原诱导的关节炎（ED50 1.6 mg/kg，BID，PO）疾病模型中显示出有效性。在大鼠（F% 50）和狗（F% 78）的药代动力学研究中观察到良好的生物利用度[2]。 |
| Target activity | IRAK4:21 nM |
| molecular weight | 432.86 |
| Molecular formula | C19H21ClN6O4 |
| CAS | 1287665-60-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: ＜1 mg/mL (insoluble or slightly soluble), Sonication and heating to 60℃ are recommended. |
| References | 1. Mitsuhiro Kondo, et al. Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats. Naunyn Schmiedebergs Arch Pharmacol. 2014 Oct;387(10):909-19. 2. JohnHynesJr, et al. Chapter Nine - Advances in the Discovery of Small-Molecule IRAK4 Inhibitors. Annu Rep Med Chem. 2014 (49):117-133. |