Inhibitors of Microsomal Prostaglandin E 2 Synthase-1 Enzyme as Emerging Anti-Inflammatory Candidates Malkeet Singh Bahia, 1 Yogesh Kumar Katare, 2 Om Silakari, 1 * Bhawna Vyas, 3 and Pragati Silakari 4 1 Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India 2 Radharaman Institute of Pharmaceutical Sciences, Bhopal, Madhya Pradesh, 462046, India 3 Department of Chemistry, Punjabi University, Patiala, Punjab, 147002, India 4 Adina institute of Pharmaceutical Sciences, Sagar, Madhya Pradesh (M.P.), 470001, India Published online 13 January 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/med.21306  Abstract: Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid (AA) into PGH 2 that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E 2 (PGE 2 ), prostacyclin I 2 (PGI 2 ), thromboxane A 2 (TXA 2 ), prostaglandin D 2 (PGD 2 ), and prostaglandin F 2 alpha (PGF 2α ). Among them, PGE 2 is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti-inflammatory therapy. For instance, nonsteroidal anti- inflammatory agents (NSAIDs), both classical nonselective (cNSAIDs) and the selective COX-2 inhibitors (coxibs) attenuate the generation of PGH 2 from AA that in turn reduces the synthesis of PGE 2 and modifies the inflammatory conditions. However, the long-term use of these agents causes severe side effects due to the nonselective inhibition of other PGs, such as PGI 2 and TXA 2 , etc. Microsomal prostaglandin E 2 synthase-1 (mPGES-1), a downstream PG synthase, specifically catalyzes the biosynthesis of COX-2- derived PGE 2 from PGH 2 , and describes itself as a valuable therapeutic target for the treatment of acute and chronic inflammatory disease conditions. Therefore, the small molecule inhibitors of mPGES-1 would serve as a beneficial anti-inflammatory therapy, with reduced side effects that are usually associated with the nonselective inhibition of PG biosynthesis. C  2014 Wiley Periodicals, Inc. Med. Res. Rev., 34, No. 4, 825–855, 2014 Key words: atherosclerosis; cancer; cyclooxygenase-2 (COX-2); microsomal prostaglandin E 2 synthase-1 (mPGES-1); prostaglandin E 2 ; rheumatoid arthritis; osteoarthritis Contract grant sponsor: Indian Council of Medical Research (ICMR); Contract grant number: 45/3/2012-BMS/BIF. Correspondence to: Dr. Om Silakari, M. Pharm; Ph.D., Assistant Professor, Department of Pharmaceutical Sci- ences and Drug Research, Punjabi University, Patiala, Postal code 147002, E-mail: omsilakari@rediffmail.com Medicinal Research Reviews, 34, No. 4, 825–855, 2014 C  2014 Wiley Periodicals, Inc.