Ligands at Free Fatty Acid Receptor 1 (GPR40).

FFA1 is a G protein-coupled receptor activated by medium- to long-chain fatty acids. FFA1 plays important roles in various physiological processes such as insulin secretion and energy metabolism. FFA1 expressed on pancreatic β-cells and intestine contributes to insulin and incretin secretion, respectively. These physiological functions of FFA1 are interesting as an attractive drug target for type II diabetes and metabolic disorders. A number of synthetic FFA1 ligands have been developed and they have contributed to our current understanding of the physiological and pathophysiological functions of FFA1 both in in vitro and in vivo studies. In addition, these synthetic ligands also provided information on the structure-activity relationships of FFA1 ligands. Further, FFA1 protein crystallized with one of the high affinity agonist leads provided useful insights for the development of more effective ligands. Among FFA1 ligands, several compounds have been further investigated in the clinical trials. Thus, FFA1 ligands have great potential as drug candidates. In this section, recent progress about FFA1 ligands and the possibility of their clinical use are described.