Prostaglandin E2 (PGE2; ) activates four E prostanoid (EP) receptors, EP1-4. EP4 is a Gs protein-coupled receptor that, by elevating the second messenger cAMP, plays important roles in bone formation and resorption, inflammation, cancer, and atherosclerosis. MF498 is a selective EP4 receptor antagonist (Ki = 0.7 nM versus a Ki > 1 μM for other EP receptors). In HEK293 cells expressing the human EP4 receptor, MF498 inhibits EP ligand induced activity with an IC50 value of 1.7 nM. In various animal models for arthritis, MF498 has been shown to inhibit inflammation without gastrointestinal toxicity (ED50 values as low as 0.02 mg/kg/day).
