Abstract
GPR40, an orphan G-protein coupled receptor that is activated by medium and long-chain fatty acids and is highly expressed in pancreatic islets, adipose depots and the gastrointestinal tract are involved in energy source recognition, absorption, storage and/or metabolism. Since its deorphanization in 2003, G-protein-coupled receptor GPR40 has emerged as a potential target for type II diabetes because it has been hypothesized to participate in the adverse effects of chronic fatty acid exposure on function of β-cell. This signifies that G-protein-coupled receptors have recently emerged as novel therapeutic targets in metabolic diseases, such as diabetes, obesity and the metabolic syndrome. Therefore it seems natural that GPR40 represents a potentially attractive target to best meet the need for novel treatments for Type II diabetes. This review describes recent advances and novel drug discovery approaches in the antidiabetic area, focusing on GPR40 modulators which have been synthesized till date and their Structure-Activity Relationship (SAR).
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