Glenmark Pharmaceuticals' new chemical entity (NCE) 'GRC 27864', which targets Microsomal Prostaglandin E synthase-1 (mPGES-1) as a novel therapeutic target in pain management is entering human trials. GRC 27864 is a potent, selective, and orally bioavailable inhibitor of mPGES-1, an enzyme which is up-regulated under inflammatory conditions.

Blocking the mPGES-1 enzyme is a novel strategy and expected to selectively inhibit increased PGE2 production during inflammation, without affecting other prostanoids of physiological importance. This selective mPGES-1 inhibitors are expected to inhibit increased prostaglandin E2 (PGE2) production in the disease state without affecting other prostanoid metabolites and, consequently, may be devoid of the gastrointestinal (GI ) and cardiovascular side effects seen with NSAIDs and COX-2 inhibitors, respectively.

The company informed that they have completed preclinical studies and phase 1 enabling GLP studies for its selected lead molecule, GRC 27864 and has filed a phase 1 application for first-in-human trial with the MHRA, UK. The phase 1 studies are to be initiated soon and are likely to get completed by January 2015. Following this, Glenmark will also be initiating a proof of concept study in patients with acute pain.

Dr Michael Buschle, chief scientific officer, Glenmark Pharmaceuticals, informed, "We are excited that our mPGES-1 discovery program is moving forward to human trials. This is another potential first-in-class molecule and there is a significant unmet medical need. This announcement also reaffirms our position globally in the development of novel pain therapies.”

PGE2 is a potent pro-inflammatory prostanoid and mediator of inflammatory response, which has been implicated in many pathological conditions including inflammation, pain, atherosclerosis, and fever. Thus, GRC 27864 has the potential to be beneficial in the chronic treatment of inflammatory diseases and associated pain. GRC 27864 is currently being developed as a drug for the potential treatment of chronic inflammatory disorders such as osteoarthritis (OA) and rheumatoid arthritis (RA).