Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity

• Published in: Journal of medicinal chemistry Vol. 64; no. 22; pp. 16598 - 16608
• Main Authors: Gorman, Declan M, Li, Xaria X, Lee, John D, Fung, Jenny N, Cui, Cedric S, Lee, Han Siean, Rolfe, Barbara E, Woodruff, Trent M, Clark, Richard J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.11.2021; Amer Chemical Soc
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Chemistry, Medicinal; Complement C5a - metabolism; Humans; Life Sciences & Biomedicine; Mammary Neoplasms, Experimental - drug therapy; Mice; Pharmacology & Pharmacy; Receptor, Anaphylatoxin C5a - agonists; Receptor, Anaphylatoxin C5a - metabolism; Science & Technology; C3A; IMMUNE; MOLECULAR ADJUVANT; ACTIVATION; PROTEIN; ANAPHYLATOXIN; ANTAGONISTS; EXPRESSION; BINDING; DECAPEPTIDE AGONISTS

The anaphylatoxin C5a is a complement peptide associated with immune-related disorders. C5a binds with equal potency to two GPCRs, C5aR1 and C5aR2. Multiple C5a peptide agonists have been developed to interrogate the C5a receptor function but none show selectivity for C5aR1. To address these limitat...