PT  - JOURNAL ARTICLE
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
TI  - Identification and Characterization of Novel Microsomal Prostaglandin E Synthase-1 Inhibitors for Analgesia
AID  - 10.1124/jpet.115.228932
DP  - 2016 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 635--644
VI  - 356
IP  - 3
4099  - http://jpet.aspetjournals.org/content/356/3/635.short
4100  - http://jpet.aspetjournals.org/content/356/3/635.full
SO  - J Pharmacol Exp Ther2016 Mar 01; 356
AB  - 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.