AS 2444697

Research use only, not for human use.

A potent, selective, orally bioavailable IRAK-4 inhibitor that potently inhibits human and rat IRAK-4 activity with subnanomolar order.

A potent, selective, orally bioavailable IRAK-4 inhibitor that potently inhibits human and rat IRAK-4 activity with subnanomolar order, >30-fold selectivity over IRAK-1; inhibited IL-1β- or TLR ligand lipopolysaccharide (LPS)-induced IL-6 production in human lung alveolar epithelial cells, fibroblast-like synoviocytes, and peripheral blood mononuclear cells; significantly reduces urinary protein excretion and preventd the development of glomerulosclerosis and interstitial fibrosis without affecting the blood pressure in mice model of chronic kidney disease.

——

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.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. 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. Animal Model:Male 6-week-old Wistar rats and Balb/c mice Dosage:0.3-3 mg/kg Administration:Single administration; orally Result:The plasma levels of IL-1β, IL-6, TNF-α, MCP-1, and aminotransferases (ALT and AST) were significantly increased.

AS2444697 | AS-2444697

Immunology/Inflammation

IRAK

IRAK

——

——

1287665-60-4

432.865

C19H21ClN6O4

>98% (HPLC)

In Vitro:?DMSO : ≥ 12.5 mg/mL (28.88 mM)

CC1=NC=CC(=C1)C2=NC(=CO2)C(=O)NC3=CN(N=C3C(=O)N)C4CCOCC4.Cl

N-[3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methylpyridin-4-yl)-1,3-oxazole-4-carboxamide hydrochloride

(-20℃)

With Ice Pack

≥ 2 years