Glenmark Pharmaceuticals has announced that GRC 27864 is entering human trials. GRC 27864 targets Microsomal Prostaglandin E synthase-1 (mPGES-1) as a therapeutic target in pain management. 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 GI (gastrointestinal) and cardiovascular side effects seen with NSAIDs and COX-2 inhibitors, respectively.
Recent reports indicate that more than 1.5 billion people worldwide suffer from chronic pain in some form with a direct correlation between incidence rates and increasing age. It is estimated that, at some point in their lives, 20% of the global adult population suffers from pain with 10% of newly diagnosed cases of chronic pain being added each year.
Despite incremental advances in opioid-based or cyclooxygenase-based therapies, there has been little success in identifying and developing treatments based upon new targets that might overcome the limitations of currently available analgesic treatments for the management of chronic pain.
Glenmark has 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.
PGE2 is a lipid mediator produced by arachidonic acid, which serves pivotal functions in disease conditions associated with fever, inflammation, and pain. mPGES-1 is a terminal enzyme in the PGE2 biosynthetic pathway and solely responsible for PGE2 synthesis during inflammation. Over expression of mPGES-1 is observed in various nonclinical animal models, such as RA, OA, atherosclerosis, experimental autoimmune encephalomyelitis, cancer, inflammatory bowel disease, multiple sclerosis, periodontitis, fibrosis, Parkinson's disease, and Alzheimer's disease.
On the contrary, mPGES-1 deleted cells produced significantly lower levels of PGE2 in response to inflammatory stimuli and were less sensitive to inflammatory and neuropathic pain, and refractory to the development of joint pathology in rodent arthritis models. Selective mPGES-1 inhibitors are expected to inhibit increased PGE2 production in the disease state without affecting other prostanoid metabolites and are, consequently, may be devoid of the GI and cardiovascular side effects seen with NSAIDs and COX-2 inhibitors, respectively, potentially making them suitable for chronic treatment of inflammatory diseases that are accompanied with pain.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Could A Star Orbit A Planet? - Just For Fun
- Japanese Soda Study—Good God(zilla)!
- Germany Versus Science, Round Two
- Bel's Temple in Palmyra Is No More
- Cannabis Use May Influence Brain Maturation In Young Males
- An Historical Moment For Diabetes
- Daratumumab Immunotherapy Agent Benefits Patients With Drug-Resistant Multiple Myeloma
- "Can light contain dark in a circle or can dark contain light in a circle?Read below why this may..."
- "The risk of different of energy of electron is of serious health risk for Dirac and matter energy..."
- "Thanks. Unfortunately, it works. The Washington Post bought this big time. It's just about impossible..."
- "Great article. Junk science seems to be at an all-time high with so many just looking to make headline..."
- "Thanks, that's an interesting idea :). If you could somehow collect enough Mercury density material..."