FFA3 agonist 1 (Compound 24) is an agonist of free fatty acid receptor 3 (FFA3). FFA3 agonist 1 regulates the health effect of intestinal microbiota by activating FFA3[1].
PBI-4050 acts as an agonist for GPR40 and as an antagonist or inverse agonist for GPR84.
BI-2081 is a GPR40 (FFAR1) partial agonist (EC50: 4 nM). BI-2081 induces glucose depending insulin secretion and reduces the plasma glucose concentration. BI-2081 can be used in the research of metabolic diseases, in particular diabetes type 2[1].
TUG-499 is a selective free fatty acid receptor 1 (FFAR1 or GPR40) (Free Fatty Acid Receptor) agonist with a pEC50 of 7.39. TUG-499 exhibits >100-fold selectivity over the related receptors FFA2, FFA3, and the nuclear receptor PPARγ and other diverse receptors, ion channels, and transporters. TUG-499 can be used for the research of type 2 diabetes[1].
GPR40 agonist 5 (compound I-14) is an orally active and potent GPR40 (G protein coupled receptor 40) agonist, with an EC50 of 47 nM. GPR40 agonist 5 decreases the levels of blood glucose and improves the glucose tolerance. GPR40 agonist 5 has sufficient effectiveness for the control of hyperglycemia state in type 2 diabetic mice[1].
LY2922470 is a potent, selective and orally available agonist of the G protein-coupled receptor 40 (GPR40), with EC50s of 7 nM, 1 nM and 3 nM for human GPR40, mouse GPR40 and rat GPR40, respectively. LY2922470 reduces glucose levels along with significant increases in insulin and GLP-1, is potential for the treatment of type 2 diabetes mellitus (T2DM)[1].
LY3104607 (LY-3104607) is a potent, selective, orally available GPR40 agonist with Ki of 15 nM, β-arrestin EC50 of 108 nM; demonstrates functional potency and glucose dependent insulin secretion in primary islets from rats; dose-dependently reduces glucose levels in vivo.
TUG-424 is a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with an EC50 of 32 nM. TUG-424 significantly increases glucose-stimulated insulin secretion at 100 nM. TUG-424 may serve to explore the role of FFA1 in metabolic diseases such as diabetes or obesity[1].
TUG-770 is a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist with EC50 of 6 nM for hFFA1.IC50 Value: 6 nM (hFFA1, EC50) [1]Target: GPR40in vitro: TUG-770 (Compound 22) displayed excellent physicochemical and in vitro ADME properties, with good aqueous solubility, good chemical stability, low lipophilicity, and decreased plasma protein binding (PPB). TUG-770 furthermore showed excellent stability toward human liver microsomes (HLM), no inhibition of selected CYP-enzymes implicated in drug-drug interactions, no P-glycoprotein (P-gp) inhibition, and good permeability in the Caco-2 cell assay [1].in vivo: Examination of TUG-770 in an acute intraperitoneal glucose tolerance test (IPGTT) in normal mice revealed a good dose dependent response with maximal reduction in glucose level reached at 50 mg/kg. The effect of TUG-770 was fully sustained after 29 days of daily oral treatment. Additional evaluation of TUG-770 in rats confirmed a significant glucose lowering effect for the high doses already after 10 min and for all doses after 30 min [1].Clinical trial:
Fasiglifam (TAK-875) is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 72 nM.
DC260126, a small-molecule antagonist of GPR40.
AS2034178 free base, a specific and orally active GPR40 agonist, exhibits glucose-dependent insulin secretion enhancement. AS2034178 free base has potential for type 2 diabetes mellitus research[1].
FAA1 agonist-1 is a potent free fatty acid receptor 1 (FFA1/ GPR40) agonist with a pEC50 of 7.54.
GPR40 Activator 1 is a potent GPR40 activator for treatment of type 2 diabetes.IC50 value:Target: GPR40Preparation of spiropiperidine derivatives for use as antidiabetic agentsBy Hamdouchi, Chafiq; Lineswala, Jayana Pankaj; Maiti, Pranab From PCT Int. Appl. (2011), WO 2011066183 A1 20110603.
Fasiglifam (TAK-875) hemihydrate is a potent, selective and orally active GPR40 agonist with EC50 of 72 nM. Fasiglifam enhances glucose-dependent insulin secretion and improves hyperglycemia in type 2 diabetic rats. Fasiglifam can induce liver injury[1][2][3][4].
GPR40/FFAR1 modulator 1 is an agonist and an allosteric modulator for Gq-coupled free fatty acid receptor 1 (GPR40/FFAR1)[1].
TUG-905 is a potent GPR40 agonist with an pEC50 value of 7.03. TUG-905 increases hypothalamic cell proliferation and survival. TUG-905 reduces body mass and increases the POMC mRNA expression[1][2].
MEDICA16, an ATP-citrate lyase inhibitor, significantly reduces intracellular TG content in gastrocnemius muscle, and this reduction is accompanied by an increase in insulin sensitivity. MEDICA16 is a selective agonist for GPR40 as well as selective partial agonists for GPR120[1][2].
AMG 837 calcium hydrate is a potent GPR40 agonist(EC50=13 nM) with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents.IC50 value: 13 nM (EC50) [1]Target: GPR40 agonistAMG 837 displayed the expected two-fold increase in potency on GPR4 (EC50 = 13 [±7] nM) compared to the racemic compound and its activity crossed over to the rat and mouse forms of GPR40 (EC50 = 23 and 13 nM, respectively). AMG 837 was found to be a partial agonist on GPR40 with maximal activity 85% of that shown by DHA under our standard assay conditions. AMG 837 is a highly potent stimulator of insulin secretion in MIN6 cells with an EC50 comparable to that seen in the aequorin Ca2+-flux assay. showedno significant activity in cell-based assays against PPARα, δ, and γ. An external panel of 64 receptors also revealed no significant activity with the exception of weak inhibition (IC50 = 3 uM) on the a2-adrenergic receptor. Overall, AMG 837 was both highly potentand selective in vitro.
Setogepram (PBI-4050) acts as an orally active agonist for GPR40 and as an antagonist or inverse agonist for GPR84[1]. Setogepram (PBI-4050) decreases renal, liver and pancreatic fibrosis[1][2]. Setogepram (PBI-4050) exerts anti-fibrotic, anti-inflammatory and anti-proliferative actions[2].
GW9508 is a potent and selective agonist for FFA1 (GPR40) with pEC50 of 7.32, 100-fold selective against GPR120, stimulates insulin secretion in a glucose-sensitive manner.IC50 value: 7.32 (pEC50) [1]Target: GPR40GW9508 is shown to be at least 100-fold selective against 220 other GPCRs, 60 kinases, 63 proteases, seven integrins and 20 nuclear receptors including PPARα, δ and γ (pEC50 4.0, 4 and 4.9, respectively). GW9508 produces a concentration-dependent increase in intracellular Ca2+ concentrations via GPR40 receptor activation and the GPR120 receptor. GW9508 is active as an agonist at both GPR40 and GPR120, it is approximately 100-fold selective for GPR40 with respect to GPR120. GW9508 produces a concentration-dependent increase (pEC50=6.14) in glucose-stimulated insulin secretion at high glucose levels (25 mM). GW9508 dose dependently stimulated insulin secretion in a glucose-sensitive manner in MIN6 cells. Furthermore, GW9508 is able to potentiate the KCl-mediated increase in insulin secretion in MIN6 cells. [1] GW9508 induced hyperpolarization and opening of KATP channels in rat β-cells. [2] GW9508 inhibits CCL17 and CCL5 expression in a pertussis toxin-sensitive manner. GW9508 further suppresses expression of IL-11, IL-24, and IL-33 induced in HaCaT cells by TNF-α and IFN-γ. GW9508 also inhibits CCL5 and CXCL10 production by normal human epidermal keratinocytes. [3]
AM-4668 is a GPR40 agonist for type 2 diabetes. EC50s of 3.6 nM and 36 nM for GPR40 in A9 cells (GPR40 IP3 assay) and CHO cells (GPR40 aequorin assay), respectively[1].
SCO-267 is an allosteric GPR40 full agonist. SCO-267 can be used for the research of chronic diseases including diabetes[1].
GPR40 agonist 1 is a potent and novel GPR40 full agonist with an EC50 of 2 nM and 17 nM for hGPR40 and rGPR40, respectively.
GPR40 Agonist 2 is a GPR40 agonist that can be used in the research of diabetes, extracted from patent WO2009054479A1.
AP5 sodium is a potent, orall active, and selective GPR40 receptor agonist with a positive allosteric modulation of endogenous ligand (AgoPAM). AP5 sodium demonstrates rat and human inositol monophosphate (IP1) EC50 values of 0.49 nM and 0.8 nM against the GPR40 receptor, respectively. AP5 sodium has the potential for type II diabetes research[1].
AM-1638 is a potent and orally bioavailable GPR40/FFA1 full agonist with an EC50 of 0.16 μM.
GW-1100 is a selective GPR40 antagonist with a pIC50 of 6.9. GW1100 acts as a GPR40 inverse agonist.
Xelaglifam is a potent GPR40 agonist. Antihyperglycaemic activity[1].
GPR40 Activator 2 is a potent GPR40 activator from patents WO 2012147516 A1, WO 2012046869A1 and WO 2011078371 A1.