PF-06650833

PF-06650833 is an inhibitor of IL-1 receptor-associated kinase 4 (IRAK4, IC50 = 0.2 nM). It is selective for IRAK4 over a panel of 268 kinases at 200 nM but also inhibits IRAK1, MAP kinase-interacting serine/threonine protein kinase 2 (MNK2), leucine-rich repeat kinase 2 (LRRK2), CDC-like kinase 4 (Clk4), and casein kinase 1gamma1 (CK1gamma1) by greater than 70% at 200 nM. PF-06650833 (100 nM) reduces secretion of DNA from primary human neutrophils stimulated by the toll-like receptor 7 (TLR7) agonist R-837 (imiquimod, Cay-14956) and decreases IFN regulatory factor 5 (IRF5) nuclear translocation induced by the synthetic TLR7/8 ligand R-848 (Cay-14806) in primary human peripheral blood mononuclear cells (PMBCs). It decreases paw volume in a rat model of collagen-induced arthritis when administered at a dose of 100 mg/kg once per day. Dietary administration of PF-06650833 reduces serum levels of the autoantibodies anti-dsDNA, anti-SSA, and anti-RNP and decreases kidney glomerular tuft area in a mouse model of systemic lupus erythematosus (SLE) induced by the isoprenoid alkane pristane.Formal Name: 1-[[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxo-2-pyrrolidinyl]methoxy]-7-methoxy-6-isoquinolinecarboxamide. CAS Number: 1817626-54-2. Synonyms: IRAK4i. Molecular Formula: C18H20FN3O4. Formula Weight: 361.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 2 mg/ml, PBS (pH 7.2): Slightly soluble. lambdamax: 230, 348, 495 nm. SMILES: COC(C(C(N)=O)=C1)=CC2=C1C=CN=C2OC[C@H]3NC([C@@H](F)[C@H]3CC)=O. InChi Code: InChI=1S/C18H20FN3O4/c1-3-10-13(22-17(24)15(10)19)8-26-18-11-7-14(25-2)12(16(20)23)6-9(11)4-5-21-18/h4-7,10,13,15H,3,8H2,1-2H3,(H2,20,23)(H,22,24)/t10-,13+,15-/m0/s1. InChi Key: JKDGKIBAOAFRPJ-ZBINZKHDSA-N.