Free fatty acid receptor (FFAR) (FFAR)

The Free fatty acid receptor (FFAR) family consists of G protein-coupled receptors (GPCRs) that act as nutrient sensors by responding to non-esterified fatty acids of various chain lengths. This family includes FFAR1 (GPR40) and FFAR4 (GPR120), which are activated by medium- and long-chain fatty acids to promote insulin secretion and anti-inflammatory signaling, as well as FFAR2 (GPR43) and FFAR3 (GPR41), which sense short-chain fatty acids produced by gut microbiota. These receptors play crucial roles in maintaining metabolic homeostasis and regulating immune responses, making them significant therapeutic targets for metabolic and inflammatory diseases. FFAR1, in particular, has been extensively studied for its ability to enhance glucose-dependent insulin secretion without the high risk of hypoglycemia associated with other antidiabetic agents. However, drug development in this space has faced challenges, most notably concerns regarding hepatotoxicity that led to the termination of clinical programs for several early candidates.

Other names

GPR40GPR41GPR43GPR120FFA1FFA2FFA3FFA4G protein-coupled receptor 40G protein-coupled receptor 41G protein-coupled receptor 43G protein-coupled receptor 120Omega-3 fatty acid receptor

Agonism, Allosteric modulation