AS2444697

AS2444697 is an orally active IRAK-4 inhibitor with an IC₅₀ of 21 nM^[1]. AS2444697 potently inhibits human and rat IRAK-4 activity. AS2444697 exhibits renoprotective effects through anti-inflammatory action^[2]. In Vivo:AS2444697 is efficacious in the rat adjuvant-induced arthritis (ED₅₀ 2.7 mg/kg, BID, PO) and the rat collagen-induced arthritis (ED₅₀ 1.6 mg/kg, BID, PO) disease models. Good bioavailability was seen in rat (F% 50) and dog (F% 78) pharmacokinetic studies^[1].
AS2444697 (0.3-3 mg/kg) significantly increases the plasma levels of IL-1β, IL-6, TNF-α, MCP-1, and aminotransferases (ALT and AST) in LPS/GalN-treated mice. Single administration of AS2444697 (0.3-3 mg/kg) dose-dependently decreases plasma levels of these all parameters, and these effects were significant at doses of 1 mg/kg or higher^[2].
After oral administration of AS2444697 (3 mg/kg) to 5/6 Nx rats, plasma, and tissue (liver and kidney) concentrations of the unchanged drug peaked at 1 h and then gradually decreased, with a terminal half-life of 2.7-2.9 h^[2].