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)