Therapeutics: Microsomal prostaglandin E synthase-1 (PTGES; mPGES-1); prostaglandin E2 (PGE2)

Cell culture, human blood and guinea pig studies identified PTGES inhibitors that could help treat arthritis-related pain. In in vitro enzymatic activity assays, two compounds based on different scaffolds inhibited PTGES activity with IC50 values of 0.94 and 241 nM. In whole human blood, each compound inhibited PGE2 production with IC50 values of 0.792 and 0.015 μM, respectively. In a guinea pig model of joint injury, each compound decreased pain compared with vehicle. Next steps could include testing the compounds in additional models of arthritis-related pain.

Eli Lilly and Co. has LY3023703, a PTGES inhibitor, in Phase II testing to treat osteoarthritis and pain. ...