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?
- Part I: Bee Deaths Mystery Solved? Neonicotinoids (Neonics) May Actually Help Bee Health
- Eosinophilic Esophagitis: Genetic Clues Of Severe Food Allergy
- Is Religion A Consolation Worth Having?
- 3X Saturated Fat In The Diet Doesn't Increase It In Blood
- Interstellar Is A Dangerous Fantasy Of US Colonialism
- Education: Stop New Age Thinking, Chalk And Talk Might Be The Best Way After All
- Extraordinary Claims: Review My Paper For $10
- "I took a look at the paper. Henry and LFB are not exaggerating. There are many serious problems..."
- "If one is a fan of the FireFly franchise they could take this movie as a sort of rip off of the..."
- "Ha! Like I said, Democrats are a lot better about PR than Republican groups are. Corporations have..."
- "From your response, you seem totally incapable of addressing anything I wrote.Experience has taught..."
- "It is a fact that throughout history much evil has been done for the sake of the believers' godsAnd..."
- Suicide risk falls substantially after talk therapy
- The Lancet: Universal health coverage for US militar veterans within reach, but many still lack coverage
- Modified DNA backbone enables success of existing and novel oligonucleotide therapeutics
- Gene in kidney may play role in high blood pressure
- Panel-based genetic diagnostic testing for inherited eye disease proves highly accurate
Books By Writers Here