MBX-2982 is a selective, orally-available G protein-coupled receptor 119 (GPR119) agonist.
APD668 is a potent GPR119 agonist with EC50 of 2.7 nM and 33 nM for hGPR119 and ratGPR119 respectively..IC50 value: 2.7 nM (EC50) [1]Target: GPR119Chronic treatment withAPD668 showed for the first time that blood glucose and glycated hemoglobin (HbA1c) levels could be significantly reduced in Zucker Diabetic Fatty (ZDF) rats over several weeks of dosing. APD668 was the ?rst compound with thismechanism of action to be progressed into clinical development for the treatment of diabetes.
Firuglipel (DS-8500a) is an orally available, potent and selective GPR119 agonist.
BMS-903452 is a potent and selective GPR119 agonist for diabetes research[1].
2-Oleoylglycerol is a dietary naturally occurring lipid. 2-Oleoylglycerol is a GPR119 agonist, with an EC50 of 2.5 μM for human GPR119 in transiently transfected COS-7 cells. 2-Oleoylglycerol stimulates glucagon-like peptide-1 (GLP-1) secretion in vivo[1][2].
APD597 is a GPR119 agonist intended for the treatment of type 2 diabetes, with EC50 of 46 nM for hGPR119.IC50 value: 46 nM (EC50) [1]Target: hGPR119The design and synthesis of a second generation GPR119-agonist clinical candidate for the treatment of diabetes is described. APD597 was selected for preclinical development based on a good balance between agonist potency, intrinsic activity and in particular on its good solubility and reduced drug-drug interaction potential. [1]
AR231453 is a potent and selective small molecule agonist of GPR119 that enhances glucose-dependent insulin secretion and glucagon-like peptide 1 (GLP-1) release; Antidiabetic agent.IC50 value: Target: GPR119in vitro: The GPR119-specific agonist AR231453 significantly increased cAMP accumulation and insulin release in both HIT-T15 cells and rodent islets. In both cases, loss of GPR119 rendered AR231453 inactive [1]. In GLUTag cells, a well-established model of intestinal L-cell function, the potent GPR119 agonist AR231453 stimulated cAMP accumulation and GLP-1 release [2].in vivo: AR231453 also enhanced glucose-dependent insulin release in vivo and improved oral glucose tolerance in wild-type mice but not in GPR119-deficient mice. Diabetic KK/A(y) mice were also highly responsive to AR231453. Orally active GPR119 agonists may offer significant promise as novel antihyperglycemic agents acting in a glucose-dependent fashion [1]. When administered in mice, AR231453 increased active GLP-1 levels within 2 min after oral glucose delivery and substantially enhanced total glucose-dependent insulinotropic peptide levels. Blockade of GLP-1 receptor signaling with exendin(9-39) reduced the ability of AR231453 to improve glucose tolerance in mice [2].
GPR119 agonist 2 (compound 43) is an orally active GPR119 agonist. GPR119 agonist 2 shows good pharmacokinetic characteristics in rodents and can effectively improve glucose tolerance in mice and rats. GPR119 agonist 2 has the potential to study type 2 diabetes[1].
DPP-4/GPR119 modulator 2 (Compound 20i) is a dipeptidyl peptidase IV (DPP-IV) inhibitor and GPR119 agonist with an IC50 of 0.22 µM for DPP-IV and an EC50 of 0.95 µM for GPR119. DPP-4/GPR119 modulator 2 can be used for diabetes research[1].
GSK2041706A (GSK706) is a potent G protein-coupled receptor 119 (GPR119) agonist. GSK2041706A can be used for the research of type 2 diabetes[1].
PSN632408 is an optimized agonist of GPR119 receptors that shows similar potency to OEA at both recombinant mouse and human GPR119 receptors, exhibiting EC50 values of 5.6 and 7.9 uM, respectively.IC50 value: 5.6/7.9 uM ( recombinant mouse/ human GPR119) [1]Target: GPR119 agonistSystemic administration of PSN632408 (30 mg/kgintraperitoneally) suppresses food intake, reduces weight gain, and white adipose tissue deposition in rats. GPR119 (previously designated SNORF25) is an orphan G protein-coupled receptor expressed predominantly in the pancreas and gastrointestinal tract in humans and in the brain, pancreas, and gastrointestinal tract in rodents. It mediates a reduction in food intake and body weight gain in rats upon treatment with oleoyl ethanolamide (OEA), an endogenous, potent agonist for PPARα. These data suggest that PSN632408 may be useful as a therapeutic agent for the treatment of obesity.
DPP-4/GPR119 modulator 1 (Compound 22) is an orally active dipeptidyl peptidase IV (DPP-IV) inhibitor and GPR119 agonist. DPP-4/GPR119 modulator 1 shows blood glucose-lowering effect and moderate inhibition on hERG channel with an IC50 of 4.9 µM. DPP-4/GPR119 modulator 1 can be used for diabetes research[1][1].
AS1269574 is a potent, orally available GPR119 agonist, with an EC50 of 2.5 μM in HEK293 cells expressing human GPR119. AS1269574 activates TRPA1 cation channels to stimulate glucagon-like peptide-1 (GLP-1) secretion. AS1269574 specifically induces glucose-dependent insulin secretion from pancreatic β-cells only under high-glucose conditions. AS1269574 has the potential for the research of type 2 diabetes[1][2].
GSK1104252A is a potent and selective GPR119 agonist. GSK1104252A can be used for type 2 diabetes research[1].
GSK1292263 is a novel GPR119 receptor agonist used for the treatment of type 2 diabetes.IC50 value:Target: GPR119in vitro: GSK-1292263 is selected from 1538 compounds by using Hypo1, the Fit-Value and Estimate of GSK-1292263 that is aligned in Hypo1 are 8.8 and 7.7 (nM), respectively [1]. in vivo: GSK-1292263 administrated at a single dose of 3-30 mg/kg in the absence of nutrients correlates with increased levels of circulating gastrointestinal peptides, including glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY) and glucagon in male Sprague-Dawley rats, the increase is enhanced following administration of glucose in the oral glucose tolerance test (OGTT). GSK-129226 significant increases in the peak insulin response and insulin AUC(0-15 min) of 30-60% compared with values in the vehicle control cohort in the intravenous glucose tolerance test in rats, this insulin upregulation correlated with a significant increase in the glucose disposal rate. GSK-1292263 is associated with a statistically significant increase in insulin immunoreactivity in pancreatic sections in a 6-week study performed in Zucker diabetic fatty rats, compared with insulin immunoreactivity in samples obtained from rats receiving vehicle control. GSK-1292263 administrated at dose of 10 or 30 mg/kg or vehicle control at 2 hours prior to insulin infusion in hyperinsulinemic-euglycemic clamps stimulates glucagon secretion without increasing blood glucose levels Sprague-Dawley rats [2].
PSN 375963 hydrochloride is a potent GPR119 agonist, with EC50s of 8.4 and 7.9 μM for human and mouse GPR119, respectively. PSN 375963 hydrochloride shows similar potency to the endogenous agonist oleoylethanolamide (OEA)[1][2].