3-Isopropyl-5-(4-(((6-(4-(methylsulfonyl)phenyl)pyridin-3-yl)oxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole

GSK1292263 is an agonist of G protein-coupled receptor 119 (GPR119; EC50 = 43.9 nM in CHO-K1 cells expressing human receptors). It inhibits increases in sterol regulatory element binding protein-1 (SREBP-1) levels induced by the LXR agonist T0901317 and increases activation of AMPK in HepG2 cells in a concentration-dependent manner. GSK1292263 also inhibits breast cancer resistant protein (BCRP) and organic anion transporting polypeptide 1B1 (OATP1B1) by 52 and 40%, respectively, when used at a concentration of 3 μM.
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. 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.