TY - JOUR T1 - Identification and Characterization of Novel Microsomal Prostaglandin E Synthase-1 Inhibitors for Analgesia JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 635 LP - 644 DO - 10.1124/jpet.115.228932 VL - 356 IS - 3 AU - Srinivasan Chandrasekhar AU - Anita K. Harvey AU - Xiao-Peng Yu AU - Mark G. Chambers AU - Jennifer L. Oskins AU - Chaohua Lin AU - Thomas W. Seng AU - Stefan J. Thibodeaux AU - Bryan H. Norman AU - Norman E. Hughes AU - Matthew A. Schiffler AU - Matthew J. Fisher Y1 - 2016/03/01 UR - http://jpet.aspetjournals.org/content/356/3/635.abstract N2 - Prostaglandin (PG) E2 plays a critical role in eliciting inflammation. Nonsteroidal anti-inflammatory drugs and selective inhibitors of cyclooxygenase, which block PGE2 production, have been used as key agents in treating inflammation and pain associated with arthritis and other conditions. However, these agents have significant side effects such as gastrointestinal bleeding and myocardial infarction, since they also block the production of prostanoids that are critical for other normal physiologic functions. Microsomal prostaglandin E2 synthase-1 is a membrane-bound terminal enzyme in the prostanoid pathway, which acts downstream of cyclooxygenase 2 and is responsible for PGE2 production during inflammation. Thus, inhibition of this enzyme would be expected to block PGE2 production without inhibiting other prostanoids and would provide analgesic efficacy without the side effects. In this report, we describe novel microsomal prostaglandin E2 synthase-1 inhibitors that are potent in blocking PGE2 production and are efficacious in a guinea pig monoiodoacetate model of arthralgia. These molecules may be useful in treating the signs and symptoms associated with arthritis. ER -