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Vanderbilt continues deal-making with GlaxoSmithKline agreement around obesity-fighting compounds

By David Schwartz
Published: February 13th, 2013

Vanderbilt University has been on fire in the deal-making arena, and continued its hot streak in a new collaboration agreement with GlaxoSmithKline (GSK) for the discovery, development and commercialization of novel therapies for severe obesity.
The new deal involves a newly identified set of compounds that target the melanocortin-4 receptor (MC4-R), which is involved in energy homeostasis and the regulation of body weight. Defective melanocortin signaling is the most common cause of severe, early-onset obesity. Vandy researcher Roger Cone, PhD, and colleagues identified a series of drug-like compounds, called positive allosteric modulators (PAMs), that “gently increase” MC4-R activity.

Previous clinical trials of drugs that directly activated every MC4 receptor throughout the brain were not successful, primarily because some individuals experienced a rise in blood pressure. In comparison, PAMs act indirectly, to “boost” only those receptors that are already being turned on by a native hormone. “Rather than activating all the receptors everywhere all the time, we just want to gently increase receptor activity twofold,” Cone says. This approach should avoid raising blood pressure in patients with partially defective melanocortin signaling, and may be effective in treating common obesity, as well, he adds.

Under the collaboration agreement, Vanderbilt will conduct pharmacology and pre-clinical testing, while GSK scientists will try to develop chemically similar compounds with improved activity and efficacy. The goal is to begin Phase I testing in humans within three years — in 2016. “It’s a very aggressive timeline,” said Cone, who discovered MC4-R and demonstrated its potential for treating obesity in the late 1990s.

The agreement with Vanderbilt is the second GSK has signed with a U.S. research institution under its Discovery Partnerships with Academia (DPAc) program. Launched in 2011, the program is designed to combine the innovations coming out of university research labs with GSK’s drug discovery expertise to develop new breakthrough medicines. Under the terms of the agreement, GSK will provide research support to Vanderbilt for three years, additional payments for meeting project milestones, and a share of royalties.

The deal marks another in a string of tech transfer successes for Vandy, which according to Cone is making good use of its state-of-the-art High Throughput Screening Facility in the Vanderbilt Institute of Chemical Biology. The facility allows for a rapid, robot-assisted screen of Vanderbilt’s “library” of 160,000 compounds.

Source: Newswise

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