Good news for obesity patients - GlaxoSmithKline (GSK) and Vanderbilt University to use positive allosteric modulators (PAMs) like melanocortin-4 receptor (MC4-R) for treating severe obesity
Singapore: GlaxoSmithKline (GSK) and Vanderbilt University have signed a collaboration agreement for R&D and commercialization of novel therapies for treating severe obesity. The focus of the research will be melanocortin-4 receptor (MC4-R), which is involved in energy homeostasis, food intake, energy expenditure and in regulation of body weight. Defective melanocortin signaling is the most common cause of severe, early-onset obesity.
Dr Roger Cone and colleagues at Vanderbilt have, with the major support of the National Institutes of Health (NIH), identified a series of drug-like compounds, called positive allosteric modulators (PAMs) that 'gently increase' MC4-R activity. Dr Cone is the chair of the Department of Molecular Physiology and Biophysics, Vanderbilt University.
Under the collaboration agreement, Vanderbilt will do the pharmacology and pre-clinical testing, while GSK scientists will try to develop chemically similar compounds with improved activity and efficacy for three years following which Dr Cone's lab will continue research on the receptor supported by NIH grant DK070332. The agreement with Vanderbilt is the second that GSK has signed with a US institution under its Discovery Partnerships with Academia (DPAc) program. Launched in 2011, the program joins the insight and creativity of academic scientists with GSK's drug discovery expertise to develop innovative medicines.
Dr Cone credited the High Throughput Screening Facility in the Vanderbilt Institute of Chemical Biology and Dr David Weaver, assistant professor, pharmacology, Vanderbilt University, with making his research possible. A rapid, robot-assisted screen of Vanderbilt's library of 160,000 compounds led to the identification of hit compounds that act on the receptor. The project was launched by Dr Jacques Pantel, who now works at the French National Institute of Health and Medical Research, Paris. Postdoctoral fellow Dr Julien Sebag led the screening with the assistance of lab manager Ms Savannah Williams, primary research assistant for the project.
Dr Cone said that, "It's a very aggressive timeline. The power of the high throughput screening resources here at Vanderbilt has allowed us to find quality small molecule hits that can go directly into the drug development pipeline. GSK has already put an outstanding team of chemists on the project, so I'm hopeful we may meet that timeline."
