Complement component 3 (C3) (C3)

Complement component 3 (C3) is the central and most abundant protein of the complement system, serving as the convergence point for the classical, lectin, and alternative activation pathways [12, 14]. Upon activation, C3 is cleaved into C3a, a potent anaphylatoxin, and C3b, an opsonin that facilitates phagocytosis and forms the C5 convertase to initiate the terminal lytic pathway [13, 15]. Dysregulation of C3 is implicated in various pathologies, including paroxysmal nocturnal hemoglobinuria (PNH), where it mediates both intravascular and extravascular hemolysis, and C3 glomerulopathy, characterized by glomerular C3 deposition [1, 6, 8]. Therapeutic targeting of C3, notably by the pegylated peptide pegcetacoplan, provides broad inhibition of the complement cascade, offering clinical benefits in PNH and geographic atrophy [2, 3, 7]. However, systemic C3 inhibition carries a significant risk of serious infections from encapsulated bacteria, necessitating prophylactic vaccinations [6, 11, 16].

Other names

C3CPAMD1Complement C3C3bC3aiC3bC3dgC3dComplement component 3b

Pegcetacoplan and other C3 inhibitors bind to C3 and its activation fragment C3b, preventing the proteolytic cleavage of C3 into C3a and C3b by C3 convertases. This action blocks the amplification of the complement cascade and the formation of downstream effectors like C5 convertase and the membrane attack complex (MAC), thereby inhibiting both intravascular and extravascular hemolysis and reducing tissue-damaging C3 deposition.