AGU654 (Compound 44) is a selective mPGES-1 inhibitor with an IC50 of 2.9 nM against mPGES-1. AGU654 inhibits mPGES-1 to block the pathway converting arachidonic acid into prostaglandin E2 (PGE2) by COX-1/2, thereby alleviating inflammatory responses, pain, and fever. In activated human monocyte-derived macrophages and human whole blood models, AGU654 selectively suppresses bacterial exotoxin-induced PGE2 production while preserving the production of other prostaglandins. In guinea pig models, AGU654 significantly alleviates fever, inflammation, and inflammatory pain, exhibiting excellent anti-inflammatory, analgesic, and antipyretic effects. AGU654 holds promise as a strategy for studying inflammatory diseases and pain.
