Complement component 3 and Complement component 5 (C3 and C5)

Complement components C3 and C5 are central proteins in the complement system, a critical arm of the innate immune response that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. C3 is the most abundant complement protein and serves as the convergence point for the classical, lectin, and alternative pathways; its cleavage leads to opsonization and the amplification of the complement cascade. C5 is located downstream of C3 and, upon activation, releases the potent chemoattractant C5a and initiates the assembly of the membrane attack complex (MAC), which mediates direct cell lysis. Dysregulation of these components is implicated in various autoimmune and inflammatory disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and geographic atrophy. Therapeutic strategies involve monoclonal antibodies or peptides that inhibit the cleavage of C3 or C5, thereby reducing systemic inflammation and preventing immune-mediated tissue damage. However, because these proteins are vital for defense against pathogens, their inhibition necessitates careful monitoring and prophylactic measures against specific bacterial infections.

Other names

C3C5Complement C3Complement C5CPAMD1CPAMD4

Drugs targeting C3 and C5 typically act as inhibitors to prevent the cleavage of these proteins into their active fragments (C3a/C3b and C5a/C5b). C3 inhibitors like pegcetacoplan bind to C3 and its activation fragment C3b, preventing the formation of C3 and C5 convertases. C5 inhibitors like eculizumab and ravulizumab bind specifically to C5, blocking its cleavage into C5a (a potent pro-inflammatory anaphylatoxin) and C5b (which initiates the formation of the membrane attack complex).