| Description | Avacopan (CCX168) is an orally administered small-molecule C5aR ( IC50 : 0.1 nM.)antagonist that blocks the effects of C5a and prevents the development of GN induced by anti-myeloperoxidase antibodies in a murine model of AAV. |
| In vivo | CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor.?CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils.?CCX168 retains high potency when present in human blood.?A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule.?CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination.?CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys[1]. |
| Target activity | C5aR:0.1 nM |
| Synonyms | CCX168 |
| molecular weight | 581.64 |
| Molecular formula | C33H35F4N3O2 |
| CAS | 1346623-17-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 10 mg/mL (17.19 mM) |
| References | 1. Bekker P, et al. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS One. 2016 Oct 21;11(10):e0164646. 2. Jayne D R W , Bruchfeld A N , Harper L , et al. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis[J]. Journal of the American Society of Nephrology, 2017:ASN.2016111179. |
| Citations | 1. González‐del‐Barrio L, Pérez‐Alós L, Cyranka L, et al.MAP‐2: CD55 chimeric construct effectively modulates complement activation.The FASEB Journal.2023, 37(11): e23256. |