International consortium develops first-in-class adiponectin receptor agonist

A compound that mimics the effects of adiponectin, a beneficial protein that is produced by fat tissue in healthy weight individuals and may exhibit protective effects against cancer, cardiovascular disease, inflammatory conditions and insulin resistance has been developed by an international consortium lead by Dr. Eva Surmacz, Associate Professor in Biology (Adjunct) and director of the Obesity and Cancer Program at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University's College of Science and Technology.

Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases.

"In general, the leaner you are, the more adiponectin you produce," says Dr. Surmacz. "Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially in the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to difficulties in converting the full size adiponectin protein into a viable drug."

"Under the direction of Dr. Laszlo Otvos, a medicinal chemist, we designed small peptides, that mimic adiponectin activity but have chemical and biological features that allowed us to convert them into a potential drug. Indeed, our leading peptide features biological activity similar to adiponectin as well as superior stability in biological fluids and acceptable toxicity profile," says Dr. Surmacz.

The leading adiponectin-based compound represents a first-in-class adiponectin receptor agonist. The study examining the efficacy of the peptide in cancer models has been published in the Oct 5, 2011 issue of BMC Biotechnology.

"The next step is to evaluate if this peptide can have any benefits in diseases other than cancer," says Dr. Sumacz. "It is possible that the peptide will be active as an insulin sensitizer and may be useful in the treatment of type 2 diabetes."

A program validating the efficacy of these molecules in pre-clinical models of cancer and other diseases is ongoing.

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