LY3023703

LY3023703 is an oral small molecule inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that regulates the biosynthesis of proinflammatory prostaglandin E2 (PGE2) downstream of cyclooxygenases COX-1 and COX-2. It was developed by Eli Lilly as a potential treatment for pain conditions including acute pain, dental pain, musculoskeletal pain, and inflammatory pain. In clinical studies in healthy volunteers, LY3023703 demonstrated potent inhibition of PGE2 synthesis without suppressing prostacyclin generation—a pharmacological profile distinct from traditional NSAIDs. However, development was discontinued after phase 1/phase 2 trials due to drug-induced liver injury caused by a reactive metabolite generated from its chemical structure[1][2][4][5].