Avacopan

Avacopan is an antagonist of the complement 5a1 (C5a1) receptor (IC50 = 0.1 nM). It is selective for C5a1 over the C5a2 receptor and chemokine-like receptor 2 (CMKLR2), also known as chemerin receptor 2 or GPR1 (IC50s = >10,000 nM for both), as well as the C3a receptor, CMKLR1, and formyl peptide receptor 1 (FPR1, IC50s = >10,000 nM for all), and over panels of 18 chemokine receptors (IC50s = >6,700 nM for all), 54 other receptors at 10 µM, and five cytochrome P450 (CYP) isoforms (IC50s = >10,000 nM for all). Avacopan (50 nM) reduces the migration of isolated cynomolgus monkey neutrophils. It also reduces C5a-induced increases in neutrophil cell surface levels of CD11b in whole blood isolated from mice with a knock-in of human C5AR1, the gene encoding the C5a1 receptor, when used at concentrations of 10 and 100 nM or when administered at doses of 0.075 or 0.15 mg/kg. Formulations containing avacopan have been used in the adjunctive treatment of severe vasculitis associated with anti-neutrophil cytoplasmic autoantibodies (ANCA).Formal Name: (2R,3S)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-methyl-3-(trifluoromethyl)phenyl]-3-piperidinecarboxamide. CAS Number: 1346623-17-3. Synonyms: CCX168. Molecular Formula: C33H35F4N3O2. Formula Weight: 581.6. Purity: >95% (mixture of isomers). Formulation: (Request formulation change), A solid. Solubility: DMF: 12 mg/ml, DMSO: 5 mg/ml, Ethanol: 3 mg/ml. lambdamax: 252 nm. SMILES: O=C(C1=C(C=CC=C1F)C)N2[C@](C3=CC=C(C=C3)NC4CCCC4)([H])[C@H](CCC2)C(NC5=CC(C(F)(F)F)=C(C=C5)C)=O. InChi Code: InChI=1S/C33H35F4N3O2/c1-20-12-15-25(19-27(20)33(35,36)37)39-31(41)26-10-6-18-40(32(42)29-21(2)7-5-11-28(29)34)30(26)22-13-16-24(17-14-22)38-23-8-3-4-9-23/h5,7,11-17,19,23,26,30,38H,3-4,6,8-10,18H2,1-2H3,(H,39,41)/t26-,30-/m0/s1. InChi Key: PUKBOVABABRILL-YZNIXAGQSA-N.