Complement C5a Receptor 1 (C5aR1), a part of the complement system, belongs to G-protein coupled receptor (GPCR) superfamily. All myeloid cells, some lymphocytes, and nonmyeloid cells (such as lung endothelial cells, alveolar and bronchial epithelial cells) expresses C5aR1. It carries out much of the functional inflammatory activity of C5a. The C5a induced inflammatory pathways has already become a therapeutic target through the application of C5aR1 antagonists. C5aR1 antagonists have the potential for the research of diseases like inflammatory bowel disease (IBD), cancer, motor neuron disease, and rheumatoid arthritis (RA). Multiple C5a peptides have been applicated for interrogating the C5a receptor function, but none of them shows selectivity for C5aR1. So far, little therapeutic application for C5aR1 activation has been developed due to the lack of tools to selectively interrogate C5aR1.

BM213 (HY-145237) is a potent and selective agonist for complement C5a receptor 1 with anti-cancer activities.

BM213 displays no C5aR2 activity and over 1000-fold selectivity over C3aR. BM213 has EC₅₀s of 59 nM and 52.8 mM for C5aR1 and C3aR, respectively. BM213 induces C5aR1-mediated calcium mobilization and pERK1/2 signaling but not β-arrestin recruitment. BM213 significantly suppresses LPS-induced IL-6 and TNFα release from human macrophages at 1 μM. Moreover, this compound is stable in serum and displays no cytotoxicity on SHSY-5Y cells. It results in a significant reduction in tumor growth in a mouse breast cancer model.

In conclusion, BM213 is a selective C5aR1 agonist. It’s a useful research tool to study C5aR1 function.