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?
- World Did NOT End On 29th July! AWFUL "Silly Season" Story - Journalists Please Be More Responsible
- Why An Extra Planet Can't Be Hidden Behind The Sun Or Above The South Pole
- My Applied National Security Paper. Being President Isn't For Idiots.
- Mind The (Risk Perception) Gap On BPA
- SYRINA: A Trojan Horse For Endocrine Disrupting Chemicals?
- The Daily Physics Problem - 5
- Why Do Consumers Participate In 'green' Programs?
- "It's a bit smaller. Chicxulub was probably about 10 km in diameter, while 1950 DA is 1.1 km in..."
- "You forgot something there donaldtrump2, the most important US Constitutional right: buy more guns..."
- "Is 1950 DA bigger than chicxclub meteor sorry that I butchered the word ..."
- "I don't think iran wants nuclear weapons.and they are signatories of NPT.if they desire nuclear..."
- "hello mark! if you mean Ms. Wilhemina Pelegrina, I really like her name. very beautiful name. I..."
- Tracking how HIV disrupts immune system informs vaccine development
- Green monkeys acquired Staphylococcus aureus from humans
- Researchers find molecular switch that triggers bacterial pathogenicity
- Scientists identify immunological profiles of people who make powerful HIV antibodies
- Breastfeeding associated with better brain development and neurocognitive outcomes