Complement component 3 is a protein of the immune system that contains 13 structural domains. C3 plays an important role in the complement system, and also promotes innate immunity. In humans, C3 mainly exists in hepatocytes.
In the classical complement pathway, C3-converting enzymes, also known as C4b2a, can catalyze complement C3 and cleave to C3a and C3b. Among them, C3a is an allergenic toxin and is a precursor of a number of cytokines. Also, it can act as a mediator of local inflammatory processes and, in chronic inflammation, as a chemoattractant for neutrophils. C3b is a regulatory agent. Factor I cleaves C3b into C3c and C3d, and C3d plays a role in enhancing B-cell responses.
At the same time, in the alternative complement pathway, C3bBb, another form of C3 convertase can also cleave C3. C3 can be activated to C3b and expose a reactive thioester, which allows it to covalently bind cell surface carbohydrates or immune aggregates. And activated C3 can further interact with Factor B. Factor D can activate Factor B, forming Bb.
Pegcetacoplan is a pegylated complement C3 Inhibitor peptide.
From: Gerber GF, Brodsky RA. Blood. 2022 Jun 9;139(23):3361-3365.
Pegcetacoplan acts effect by binding with complement component 3 (C3) and its activation fragment C3b. And then it controls the cleavage of C3 and the generation of downstream effectors of complement activation. Therefore, Pegcetacoplan can regulate both C3b-mediated extravascular haemolysis and terminal complement-mediated intravascular haemolysis.
Besides, Pegcetacoplan plays important roles in the research of complement-mediated diseases, including age-related macular degeneration, C3 glomerulopathy, Geographic atrophy (GA), and autoimmune haemolytic anaemia. Moreover, Pegcetacoplan treatment can increase D-dimer normalization. Additionally, it reduces the incidence of thrombotic events in patients with paroxysmal nocturnal hemoglobinuria (PNH) who are complement-inhibitor naïve or remained anemic after ECU treatment in the clinical trial.
In conclusion, Pegcetacoplan is a polyethyleneglycolated complement C3 inhibitory peptide that can be used in the study of complement-mediated diseases.
 David S Liao, et al. Ophthalmology. 2020 Feb;127(2):186-195.
 Sheridan M Hoy, et al. Drugs. 2021 Aug;81(12):1423-1430.