Structure and function of pegcetacoplan. (A) Schematic of pegcetacoplan structure. Pegcetacoplan is a PEGylated peptide of the compstatin family composed of 2 identical cyclic peptides covalently bound to a PEG molecule. Compstatin and its analogs bind in a shallow groove in the C-terminal fragment of the complement C3 β-chain. There is extensive interaction between C3 and compstatin. The green circles represent hydrophobic interactions and hydrogen bonding between compstatin derivatives and C3.²³ (B) Complement pathway inhibitors approved for clinical use or in trial for PNH and their sites of inhibition. Pegcetacoplan and other compstatin family derivatives sterically inhibit the interaction between C3 and the C3 convertase through binding to C3 or C3b. Iptacopan (factor B inhibitor), danicopan (factor D inhibitor), and BCX9930 (factor D inhibitor) are oral proximal complement inhibitors in phase 2 and 3 clinical trials for PNH, both as monotherapy and in combination with a C5 inhibitor.