Complement C3 (C3) (C3)

Complement C3 is the central and most abundant protein of the complement system, playing a pivotal role in the innate immune response (UniProt P01024). It serves as the essential convergence point for the classical, lectin, and alternative pathways of complement activation. Upon activation, C3 is enzymatically cleaved into C3a, which mediates inflammation, and C3b, which facilitates opsonization and the formation of C5 convertase (StatPearls, Physiology, Complement Cascade). Dysregulation of C3 is a primary driver in diseases such as paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy, and age-related macular degeneration (AMD) (PubMed: 33159234). Therapeutic agents like pegcetacoplan bind to C3 and its activation fragment C3b, preventing the cleavage of C3 and thereby inhibiting all downstream complement-mediated effector functions (DrugBank DB15578). This broad inhibition is particularly effective in treating extravascular hemolysis and chronic inflammatory conditions where proximal complement control is required. However, because C3 is vital for opsonizing pathogens, its inhibition increases the risk of infections by encapsulated bacteria, necessitating prophylactic vaccinations (FDA Label: Empaveli).

Other names

Complement component 3CPAMD1C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1C3a anaphylatoxinC3bC3cC3dC3gC3dgiC3b

C3 inhibitors bind to the C3 protein and its activation fragments, sterically hindering the interaction between C3 and the C3-convertases. This prevents the cleavage of C3 into C3a and C3b, effectively shutting down the amplification loop and the formation of C5 convertase, which halts the entire downstream complement cascade including the membrane attack complex (MAC) formation (PubMed: 28813336).