DA-1241 (Vanoglipel, DA1241) is a novel potent, highly selective GPR119 agonist, activates human GPR119 (EC50=4.37 nM) in increasing cAMP levels in GPR119-overexpressing HEK293 cells.
DA-1241 increased cAMP levels via activated mouse GPR119 (EC50, 71.5 nM) and rat GPR119 (EC50, 156 nM).
DA-1241 showed no significant activity against 156 off-target proteins at 10 uM, including human GLP-1 receptor and human GPR40.
DA-1241 stimulated insulin secretion in hamster insulinoma HIT-T15 cells with EC50 of 22.3 nM, association with enhanced human insulin promoter activity.
DA-1241 significantly reduced postprandial glucose excursion, significantly preserved β-cell mass with reduced PDX1 levels in the islets from HFD/STZ diabetic mice.
DA-1241 reduced triglyceride content in the liver thereby improved fatty liver, reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver, reduced autophagic flow in HepG2 cells.