FFAR1
Synonyms
FFAR1, Free Fatty Acid Receptor 1, G-Protein Coupled Receptor 40, GPR40, G Protein-Coupled Receptor 40, GPCR40, FFA1R
Description
Free fatty acid receptor 1 (FFA1), also known as GPR40, is a class A G-protein coupled receptor that in humans is encoded by the FFAR1 gene.G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation. Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway. Mediates the anti-inflammatory effects of omega-3 polyunsaturated fatty acids (PUFAs) via inhibition of NLRP3 inflammasome activation.
KO Status
RenMab: F2 (-/-)
Drug Information
Drugs in clinical trials: 5
Latest Research Phase: Phase 3 Clinical
Drug Name
Code
Phase
Company
Indications
Clinical Trials
Setogepram
PBI-4050
Phase 3 Clinical
Prometic Life Sciences
Cystic Fibrosis, Diabetes Mellitus, Type 2, Idiopathic Pulmonary Fibrosis, Metabolic Syndrome, Alstrom Syndrome, Diabetes Mellitus
HOB-047
HD-6277, HOB-047, GPR-6277, HDNO-1605
Phase 1 Clinical
Hyundai Pharmaceutical
Diabetes Mellitus, Type 2
CPL-207-280
CPL-207280, CPL-207-280
Phase 1 Clinical
Celon Pharma
Diabetes Mellitus, Type 2
SCO-267
SCO-267
Phase 1 Clinical
Takeda
Hepatitis, Alcoholic, Diabetes Mellitus, Type 2, Obesity
PBI-4547
PBI-4547
Phase 1 Clinical
Prometic Life Sciences
Non-alcoholic Fatty Liver Disease, Liver Cirrhosis, Obesity, Diabetes Mellitus
Fuglifam
Phase 1 Clinical
Jiangsu Hengrui Medicine Co Ltd
Diabetes Mellitus, Type 2
PBI-4425
PBI-4425
Preclinical
Prometic Life Sciences
Scleroderma, Systemic, Pulmonary Fibrosis, Diabetic Nephropathies, Acute Lung Injury
IDG-16177
IDG-16177
Preclinical
Ildong Pharmaceutical
Diabetes Mellitus, Type 2
HXP-0057
HXP-0057, HXP0057-SS
Preclinical
Fujian Haixi New Pharmaceutical Co Ltd
Diabetes Mellitus
ID-11014
ID-11014
Preclinical
Ildong Pharmaceutical
Diabetes Mellitus, Type 2
References
Title
Authors
Source
A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1
Sawzdargo M., George S.R., Nguyen T., Xu S., Kolakowski L.F. Jr., O'Dowd B.F.,
Biochem. Biophys. Res. Commun. 239:543-547(1997)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)
The MGC Project Team,
Genome Res. 14:2121-2127(2004)
The orphan G protein-coupled receptor GPR40 is activated by medium and long-chain fatty acids
Briscoe C.P., Tadayyon M., Andrews J.L., Benson W.G., Chambers J.K., Eilert M.M., Ellis C., Elshourbagy N.A., Goetz A.S., Minnick D.T., Murdock P.R., Sauls H.R. Jr., Shabon U., Spinage L.D., Strum J.C., Szekeres P.G., Tan K.B., Way J.M., Muir A.I.,
J. Biol. Chem. 278:11303-11311(2003)
GPR40 gene expression in human pancreas and insulinoma
Tomita T., Masuzaki H., Noguchi M., Iwakura H., Fujikura J., Tanaka T., Ebihara K., Kawamura J., Komoto I., Kawaguchi Y., Fujimoto K., Doi R., Shimada Y., Hosoda K., Imamura M., Nakao K.,
Biochem. Biophys. Res. Commun. 338:1788-1790(2005)
Identification of residues important for agonist recognition and activation in GPR40
Sum C.S., Tikhonova I.G., Neumann S., Engel S., Raaka B.M., Costanzi S., Gershengorn M.C.,
J. Biol. Chem. 282:29248-29255(2007)
Two arginine-glutamate ionic locks near the extracellular surface of FFAR1 gate receptor activation
Sum C.S., Tikhonova I.G., Costanzi S., Gershengorn M.C.,
J. Biol. Chem. 284:3529-3536(2009)
Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signaling through activation of free fatty acid receptor GPR40
Kruska N., Reiser G.,
Neurobiol. Dis. 43:465-472(2011)
Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation
Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., Guarda G., Tian Z., Tschopp J., Zhou R.,
Immunity 38:1154-1163(2013)
A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1
Yabuki C., Komatsu H., Tsujihata Y., Maeda R., Ito R., Matsuda-Nagasumi K., Sakuma K., Miyawaki K., Kikuchi N., Takeuchi K., Habata Y., Mori M.,
PLoS ONE 8:E76280-E76280(2013)
Alteration of the glucagon axis in GPR120 (FFAR4) knockout mice: a role for GPR120 in glucagon secretion
Suckow A.T., Polidori D., Yan W., Chon S., Ma J.Y., Leonard J., Briscoe C.P.,
J. Biol. Chem. 289:15751-15763(2014)