MRGPRX2 Antagonist EP262 Potently Inhibits Agonist-Induced Mast Cell Degranulation In Vitro and In Vivo

Abstract

Mas-Related G-Protein Coupled Receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent mast cell activation and degranulation in response to a wide variety of structurally diverse compounds including neuropeptides and host defense peptides and has been implicated in inflammatory conditions involving mast cell activation. Our objective was to develop and characterize a small molecule antagonist that potently inhibits MRGPRX2-mediated mast cell degranulation as a novel therapeutic approach for mast cell-mediated diseases.