AS-2444697

Description

AS-2444697 is an inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4; IC₅₀ = 21 nM). It is greater than 30-fold selective for IRAK4 over a panel of 146 kinases, but is less than 10-fold selective over PDGFRα, PDGFRβ, TrkA, TrkC, CLK1, Itk, and FLT3. AS-2444697 inhibits IL-1β-induced IL-6 production and LPS-induced TNF-α production in cellular assays (IC₅₀s = 250 and 47 nM, respectively). It is efficacious in rat models of adjuvant- and collagen-induced arthritis (ED₅₀s = 2.7 and 1.6 mg/kg, respectively). AS-2444697 (0.3-3 mg/kg, twice daily) reduces urinary protein excretion, the development of interstitial fibrosis and glomerulosclerosis, and renal mRNA expression of genes encoding IL-1β, IL-6, TNF-α, and chemokine (C-C motif) ligand 2 (CCL2) without affecting blood pressure in the 5/6 nephrectomized rat model of chronic kidney disease.

Uses

AS2444697 has been used as an interleukin-1R-associated kinase 4 (IRAK4) inhibitor to study the role of interleukin (IL)-1/IL-33 signaling in the development of endometriosis using a mouse model of endometriosis. It has also been used to study its dose-dependent effect on the C-X-C motif chemokine ligand 8 (CXCL8) gene expression

Biochem/physiol Actions

AS2444697 is a potent and selective inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK-4) that suppresses the progression of chronic renal failure via anti-inflammatory action.

storage

Desiccate at RT