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Highlights of the article, "Targeting bile acid signaling for metabolicdiseases," authored by Drs. Charles Thomas, Roberto Pellicciari, MarkPruzanski, Johan Auwerx and Kristina Schoonjans, include:
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-- Bile acids serve as metabolic integrators, activating major signalingpathways regulated by nuclear hormone receptors including the farnesoid Xreceptor (FXR) and G protein-coupled receptors (GPCRs) such as TGR5.
-- Bile acids play a major role in lipid metabolism and homeostasis. Forexample, bile acid activation of FXR results in a decrease in serumtriglyceride levels.
-- The activation of TGR5 by bile acids increases energy expenditure andreduces diet-induced obesity. Conversely, "knockout" animal models engineeredto lack TGR5 show a tendency towards weight gain.
-- Bile acids have broad effects on glucose homeostasis, including adecrease in gluconeogenesis (glucose synthesis by the liver). These effectshave been attributed primarily to activation of FXR. Additionally, mice thatlack FXR have impaired glucose tolerance and are insulin-resistant.
Dr. Schoonjans, Ph.D., a group leader at the Ecole Polytechnique Federalede Lausanne commented, "Our research efforts have uncovered a number ofendocrine effects mediated by bile acids acting on receptors such as FXR andTGR5. This review is one of the first to provide a comprehensive summary ofwhat is now known about bile acid signaling and its relevance for metabolicfunction. From this broad viewpoint, we can see the potential for identifyingimportant new therapeutics that can address a number of important disorders."
Dr. Pruzanski, founder, President and CEO of Intercept Pharmaceuticals,commented, "At Intercept, we have proprietary insight into the rational designof potent FXR and TGR5 agonists derived from bile acid scaffolds. To date, wehave advanced our lead compound, INT-747, a first-in-class FXR agonist, intothree ongoing Phase II trials. The innovative research being reported in thecurrent issue of Nature Reviews provides additional support for our programs,and we look forward to reporting the progress of our discovery and developmentefforts in the appropriate forums."
About Intercept Pharmaceuticals
Intercept is a clinical stage biopharmaceutical company focused ondiscovering and developing small molecule drugs for the treatment of chronicfibrotic and metabolic diseases. The company's scientists and affiliatedresearchers have published extensively on the role of bile acid signaling viathe nuclear hormone receptor FXR and the G protein-coupled receptor TGR5.These receptors are key mediators of energy homeostasis and are involved inmaintaining integral functions of the liver, intestine and kidney, organsexposed to bile acid flux. The company's chemocentric discovery programs arebased on proprietary expertise in the rational design and synthesis of naturaland synthetic small molecule derivatives targeting FXR, TGR5 and other relatedtargets. For more information on Intercept, please visit the company's websiteat www.interceptpharma.com.
SOURCE Intercept Pharmaceuticals
