1287665-60-4

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.

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.

IRAK4: 21 nM (IC₅₀)

Desiccate at RT

[1] J. HYNES S N. Chapter Nine - Advances in the Discovery of Small-Molecule IRAK4 Inhibitors[J]. Annual Reports in Medicinal Chemistry, 2014, 49 1: 117-133. DOI: 10.1016/b978-0-12-800167-7.00009-2
[2] MITSUHIRO KONDO. Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats.[J]. Naunyn-Schmiedeberg’s archives of pharmacology, 2014, 387 10: 909-919. DOI: 10.1007/s00210-014-1023-z