Complement C5
A protein in the complement cascade that, when cleaved, generates C5a (a potent inflammatory mediator) and C5b (which initiates the membrane attack complex). Zilucoplan is a peptide inhibitor of C5 that prevents both inflammatory signalling and cell membrane damage in myasthenia gravis.
Technical Context
C5 (190 kDa glycoprotein, synthesised primarily in the liver) is the convergence point of all three complement activation pathways. C5 convertase (C4b2a3b for classical/lectin, C3bBbC3b for alternative) cleaves C5 into: C5a (74 amino acid anaphylatoxin — binds C5aR1/CD88, a GPCR on neutrophils, macrophages, mast cells → chemotaxis, degranulation, oxidative burst, cytokine production; one of the most potent inflammatory mediators) and C5b (initiates terminal complement complex assembly → C5b-6, C5b-7 (membrane-inserting), C5b-8, C5b-9n/MAC). Therapeutic C5 inhibition: eculizumab (monoclonal antibody — first approved complement inhibitor, for PNH and aHUS), ravulizumab (longer-acting anti-C5 antibody), and zilucoplan (macrocyclic peptide C5 inhibitor — the only peptide-based complement inhibitor, offering SC self-administration advantage over IV antibody infusions). Zilucoplan binds C5 at a different epitope than eculizumab, potentially maintaining activity in some eculizumab-resistant C5 polymorphisms.