Drug Discovery Opinion

Metabolic syndrome is a combination of medical disorders that increase the risk of developing cardiovascular disease, diabetes and obesity. A 39-residue synthetic peptide, Exenatide, which is approved for the treatment of type 2 diabetes, acts by mimicking the action of endogenous glucagon-like peptide-1 (GLP-1), a regulator of glucose metabolism and insulin secretion.

Researchers have now shown that chronic administration of a non-peptide molecule, Boc5, can induce weight loss and increase insulin sensitivity in a mouse model of diabetes and obesity by binding to the receptor for GLP-1. Boc5 is the only non-peptide molecule reported so far that behaves as a full GLP-1 mimetic in vitro and in vivo. Although Boc5 itself does not have the properties of a ‘drug-like’ molecule, it may represent a starting point for the discovery of orally bioavailable agents with the potential to treat metabolic disorders.

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