Complement component 5a receptor 1 (C5aR1) (C5aR1)

Complement component 5a receptor 1 (C5aR1, also designated CD88 or C5R1) is a seven-transmembrane G protein-coupled receptor that mediates the pro-inflammatory effects of complement fragment C5a, a potent 74-amino acid anaphylatoxin generated during complement cascade activation. C5aR1 is expressed ubiquitously on immune cells, particularly macrophages, neutrophils, and T cells, where it drives chemotaxis, anaphylataxis, and inflammatory cytokine release through Gαi and Gα16 signaling. Dysregulated C5a-C5aR1 signaling is implicated in numerous inflammatory and autoimmune diseases, including rheumatoid arthritis, ANCA-associated vasculitis, atypical hemolytic uremic syndrome, and sepsis, as well as in drug-induced toxicities such as chemotherapy-induced peripheral neuropathy. As a downstream complement intervention point, C5aR1 antagonists offer selective suppression of pro-inflammatory signaling while preserving critical immune surveillance functions; the oral C5aR1 antagonist CCX168 has demonstrated clinical efficacy in ANCA-associated renal vasculitis comparable to or exceeding standard corticosteroid-based therapy. The receptor's well-characterized ligand-binding site, consisting of primary and secondary interaction domains, supports rational drug design and development of highly selective modulators for precision therapeutic applications in complement-mediated diseases.

Other names

C5a receptorCD88C5R1C5aR (generic term, though often refers specifically to C5aR1)GPR77 (alternative designation, though this more commonly refers to C5L2)

Competitive antagonism — selective and competitive blockade of C5a binding to C5aR1. Selective pro-inflammatory signaling blockade — downstream intervention that suppresses major clinical manifestations of excessive complement activity while preserving key immune functions like opsonization. Signal transduction inhibition — blocking intracellular signaling via NFκB/P38 pathways and c-Fos activation. Receptor occupancy — preventing ligand-induced receptor activation without disrupting the broader complement cascade.