Compstatin binds to complement component C3 and inhibits complement activation with IC50 of 12 μM.
Compstatin binds to native C3 and inhibits its cleavage by C3 convertase. Binding of Compstatin to native C3 is a multistep reaction that is preferred over its binding to the C3 fragments C3b and C3c. N-acetylation of Compstatin provides stability against enzymatic degradation[1]. Compstatin features a high selectivity for human and primate C3. While binding to C3 from baboons and other primates shows comparable interaction profiles as its human counterpart, no binding is detected for C3 from lower mammalian species such as mice, rats, guinea pigs, rabbits, or pigs[3].
Compstatin completely inhibits in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug. In the extracorporeal circulation model, Compstatin inhibits the generation of C3a and C5a, the formation of the membrane attack complex, and CD11b expression on neutrophils (PMNs). The peptide also inhibits binding of C3/C3 fragments, PMNs, and monocytes to the polymer surface[2].
[1] Sahu A, et al. J Immunol. 2000, 165(5):2491-9. [2] Soulika AM, et al. Clin Immunol. 2000, 96(3):212-21. [3] Mastellos DC, et al. Eur J Clin Invest. 2015, 45(4):423-40.