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Cell Metabolism Publishes Novel TGR5-Mediated Mechanism for the Treatment of Diabetes and Obesity
Date:9/1/2009

NEW YORK, Sept. 1 /PRNewswire/ -- Bile acids are known to be key regulators of lipid, glucose and overall energy metabolism. Bile acid activation of the G protein-coupled receptor TGR5 has been shown to induce energy expenditure in muscle and brown fat, thereby conferring resistance to weight gain. Now, a paper published in the current issue of Cell Metabolism (Vol. 10, Issue 3, Sept. 2, 2009) elaborates on a separate TGR5-regulated mechanism in the gut that drives secretion of the hormone glucagon-like peptide (GLP-1) and resulting insulin sensitization.

The paper reports on the mechanism of action of the selective TGR5 agonist INT-777, providing a clear rationale for its potential as a novel treatment in diabetes, obesity and associated metabolic disorders. INT-777 is a patent-pending modified human bile acid that is currently being advanced to an IND by Intercept Pharmaceuticals, Inc. This proprietary compound was discovered by the company's scientific founder and head of medicinal chemistry, Professor Roberto Pellicciari. The newly published results were generated through a longstanding exclusive Intercept research collaboration with Professor Pellicciari and his medicinal chemistry team at the University of Perugia (Italy), together with Professor Johan Auwerx and Dr. Kristina Schoonjans who lead a molecular biology and metabolic phenotyping group at the Ecole Polytechnique Federale de Lausanne (EPFL).

Highlights of the Cell Metabolism paper, titled "TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis", authored by Dr. Charles Thomas, et al., include:

  • INT-777, a derivative of the primary human bile acid cholic acid, is a potent and selective TGR5 agonist.
  • INT-777 induces the release of GLP-1 in the gut in a TGR5-dependent manner, an effect that is markedly enhanced when the compound is given in combination with
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SOURCE Intercept Pharmaceuticals, Inc.
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