AS-2444697 (hydrochloride)

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 PDGFRalpha, PDGFRbeta, TrkA, TrkC, CLK1, Itk, and FLT3. AS-2444697 inhibits IL-1beta-induced IL-6 production and LPS-induced TNF-alpha 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-1beta, IL-6, TNF-alpha, and chemokine (C-C motif) ligand 2 (CCL2) without affecting blood pressure in the 5/6 nephrectomized rat model of chronic kidney disease.Formal Name: N-[3-(aminocarbonyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methyl-4-pyridinyl)-4-oxazolecarboxamide, monohydrochloride. CAS Number: 1287665-60-4. Molecular Formula: C19H20N6O4 . HCl. Formula Weight: 432.9. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: soluble. lambdamax: 271 nm. SMILES: O=C(N)C1=NN(C2CCOCC2)C=C1NC(C3=COC(C4=CC=NC(C)=C4)=N3)=O.Cl. InChi Code: InChI=1S/C19H20N6O4.ClH/c1-11-8-12(2-5-21-11)19-23-15(10-29-19)18(27)22-14-9-25(24-16(14)17(20)26)13-3-6-28-7-4-13,/h2,5,8-10,13H,3-4,6-7H2,1H3,(H2,20,26)(H,22,27),1H. InChi Key: FGNHLIIFEDYNFZ-UHFFFAOYSA-N.