C3a Inhibitors

Chemical inhibitors of C3a play crucial roles in modulating the function of this protein by employing various mechanisms of action. Eculizumab, for instance, targets the C5 protein and its inhibitory action results in downstream effects that include a reduction in C3a production. This is because the cleavage of C5 into C5a and C5b is a key step in the complement cascade that can lead to an amplification loop resulting in the further cleavage of C3 into C3a. By preventing the formation of C5a and C5b, eculizumab indirectly reduces the generation of C3a. Compstatin, along with its variant Potassium compstatin, directly binds to C3, preventing its cleavage into C3a and C3b. By inhibiting this cleavage, Compstatin stops the formation of C3a right at the source, thereby curtailing its presence and subsequent activity.

On the other hand, PMX-53 and SB 290157 are chemicals that target the C3a receptor. By acting as antagonists to this receptor, these compounds prevent C3a from interacting with its receptor, thus inhibiting the function of C3a without affecting its production. Similarly, K-76 monocarboxylic acid is known to bind to C3, inhibiting its conversion to C3a and, as a result, decreasing the functional activity of C3a. Nafamostat, which is a broad-spectrum serine protease inhibitor, indirectly reduces the formation of C3a by inhibiting the serine proteases necessary for the cleavage of C3. Epsikapron, by inhibiting plasminogen activation, also contributes to the reduction of C3a formation by decreasing plasmin-mediated proteolysis of C3. Coversin, similar to eculizumab, binds to C5 and by doing so, it also contributes to the suppression of C3a formation through its influence on the complement system's amplification loop.