Beta-Arrestin Biased GPCR Agonists for Inflammation and Metabolic Disease

Background

It has been shown recently that in addition to their classical role in desensitizing G protein coupled receptors (GPCR’s), beta-arrestins can act as signaling molecules  independently and certain ligands (biased ligands)  can selectively activate one pathway but not the other .  Different biological responses have been observed with such beta-arrestin biased agonists, compared with traditional GPCR therapeutics designed to activate G-proteins.  However, the lack of well characterized ligands for the beta-arrestin pathway demonstrates there is a need   for effective screening methods to obtain selective  therapeutics  that could avoid  the side effects of mediating G-protein signaling.

Technology Description

UC San Diego researchers have developed screening methods for beta-arrestin2 biased agonists that bind GPR120  and  methods for treating inflammation via activation of a beta-arrestin2 dependent signaling pathway .  Data obtained using a model compound to activate the GPCR suggests a novel role for this GPCR in modulating inflammatory responses through the beta-arrestin pathways. Model compounds investigated include DHA and EPA which do not activate the beta-arrestin1 pathway

Applications

Treatment of disorders involving inflammation including diabetes, obesity, arthritis, IBD, and neurodegeneration

State Of Development

Demonstration of anti-inflammatory response in in-vitro cellular assays.

Patent Status

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• Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Olefsky et al.; Trends Pharmacol Sci. 2011 Sep;32(9):543-50 (Review) . - 06/12/2011
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