�Historically, bile acids get been
recognised primarily as natural detergents that order the absorption of
dietary lipids and cholesterol homeostasis. However, late research
advances provide grounds that bile acids have broader systemic endocrine
functions, acting as important mediators of glucose metabolism and insulin
signaling. The featured article in the current issue of Nature Reviews Drug
Discovery (Vol. 7, Number 8, August 2008) describes wherefore bile caustic receptors
are promising targets for drug development in obesity, character 2 diabetes,
atherosclerosis and other continuing metabolic disorders such as nonalcoholic
steatohepatitis.
Highlights of the article, "Targeting bile acid signal for metabolic
diseases," authored by Drs. Charles Thomas, Roberto Pellicciari, Mark
Pruzanski, Johan Auwerx and Kristina Schoonjans, include:
-- Bile acids dish as metabolic integrators, activating major
signal pathways regulated by nuclear hormone receptors including the
farnesoid X receptor (FXR) and G protein-coupled receptors (GPCRs) such as
TGR5.
-- Bile acids play a major role in lipid metamorphosis and homeostasis.
For example, bile caustic activation of FXR results in a decrease in serum
triglyceride levels.
-- The activation of TGR5 by bile acids increases energy expenditure
and reduces diet-induced fleshiness. Conversely, "knockout" animal models
engineered to lack TGR5 show a tendency towards weight gain.
-- Bile acids cause broad personal effects on glucose homeostasis, including a
decrement in gluconeogenesis (glucose synthesis by the liver). These effects
have been attributed primarily to activation of FXR. Additionally, mice
that lack FXR have impaired glucose tolerance and ar insulin-resistant.
Dr. Schoonjans, Ph.D., a group leader at the Ecole Polytechnique
Federale de Lausanne commented, "Our research efforts have exposed a
number of internal secretion effects mediated by gall acids performing on receptors such
as FXR and TGR5. This review is one of the number one to put up a comprehensive
summary of what is now known about bile acid sign and its relevance
for metabolic function. From this broad vantage point, we pot see the potential
for identifying of import 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
design of stiff FXR and TGR5 agonists derived from bile acid scaffolds. To
date, we have innovative our lead compound, INT-747, a first-in-class FXR
agonist, into trey ongoing Phase II trials. The innovative research existence
reported in the flow issue of Nature Reviews provides extra support
for our programs, and we look forward to reporting the advance of our
discovery and development efforts in the appropriate forums."
About Intercept Pharmaceuticals
Intercept is a clinical stage biopharmaceutical company focused on
discovering and development small molecule drugs for the treatment of
chronic fibrotic and metabolic diseases. The company's scientists and
affiliated researchers have published extensively on the office of bile acid
signal via the nuclear internal secretion receptor FXR and the G protein-coupled
receptor TGR5. These receptors are key fruit mediators of energy homeostasis and
are involved in maintaining integral functions of the liver, intestine and
kidney, organs exposed to bile
