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Diabetes R & D Pipeline: DGAT1 Inhibitors
BioPolaris, Feb 2010, Pages: 7
DGAT1 inhibitors, as promising compounds for the treatment of obesity and diabetes, acquired attention in 2007 when Pfizer, Inc. (USA) and Bristol-Myers Squibb Co. (USA) finalized their agreement for the worldwide cooperation to research, develop and commercialize DGAT-1 inhibitors. However, further interest in this type of therapeutic compounds was low, and presently only five companies are developing total of four products.
DGAT1 (diacylglycerol acyl transferase-1) enzyme inhibitors are lipid metabolism modifies that positively catalyzes triglyceride synthesis and fat storage. So far, several DGAT inhibitors of natural and synthetic origin were reported. In preclinical studies with obese animals, DGAT1 inhibitors induced weight loss, decreased blood lipid levels, and improved insulin sensitivity and glucose tolerance.
Obesity is characterized by the accumulation of triacylglycerol in adipocytes, with its synthesis catalyzed by DGAT1 iso-enzyme. DGAT1 increases plasma low-density lipoprotein (LDL) concentrations, may promote obesity, and consequently is considered as potential therapeutic target for the treatment of obesity and diabetes.
The publisher found only four investigational DGAT1 inhibitors presently undergoing development, of which one is in Phase II, one has completed Phase I clinical trial, and two are in preclinical stage of development. For PF-04415060 (BAY 74-4113) development was terminated in preclinical stage. Total of five companies are developing DDGAT1 inhibitors for the treatment of diabetes and obesity.
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