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?
- A Book By Guido Tonelli
- Is Corbyn Right About The Bomb?- Op Ed
- Global Warming Has Made Global Warming Harder To Show
- Petition To Youtube To Halt Ads On Doomsday Videos - They Make The Vulnerable Suicidal
- TSCA Reform Casualties Likely Start with Asbestos
- March Against Monsanto Claims Vaccines Cause Cancer
- California Methane Caps Could Hurt Organic Farming Most
- "YouTube is massive for this subject on nibiru its horrible stuff to watch really scares alot of..."
- "No, it doesn't exist, can't exist. The ideas just don't work as a planet in our solar system. Sorry..."
- "So nibiru is really not coming then its just been scaring me for a while mr walker.Casey ..."
- "Oh there certainly can be undiscovered planets. You can choose to call them Nibiru if you wish..."
- "It's nothing unusual as we get flybys every day. Actually two flybys is fewer than usual.It's ..."
- Chemical weapons are still being used in Iraq but the Obama administration doesn't talk about it
- Why psychology lost its soul - science replaced it
- Jim Crow internet is pushing back against Black Lives Matter
- Ben & Jerry's: Global warming is changing the flavor of ice cream
- Laterality: Finding out about the human mind through stone