WB403

WB403 is an orally active TGR5 activator with an EC₅₀ of 5.5 μM against human TGR5. WB403 activates TGR5 to stimulate downstream signaling pathways, promote GLP-1 secretion, improve glucose tolerance in mice with type 2 diabetes, and reduce fasting blood glucose, postprandial blood glucose, and HbA1c levels. WB403 increases pancreatic β-cell mass, restores the distribution of α-cells and β-cells in islets, and does not induce gallbladder filling in mouse models. WB403 can be used for the research of type 2 diabetes^[1]. In Vitro:WB403 (1-20 μM; 16 h) dose-dependently activates human TGR5 in transiently transfected 293T cells with an EC₅₀ of 5.5 μM, as measured by a CRE-luciferase reporter assay^[1].
WB403 (10 μM; 30 min) significantly stimulates active GLP-1 secretion from human NCI-H716 enteroendocrine cells^[1]. In Vivo:WB403 (50-100 mg/kg; p.o.; daily; 8 weeks) significantly reduces fasting and postprandial blood glucose levels, decreases HbA_1c levels, and restores islet area in type 2 diabetic ICR mice induced by high-fat diet/Streptozotocin (HY-13753)^[1].
WB403 (50-100 mg/kg; p.o.; daily; for 4 consecutive weeks) significantly reduces fasting and postprandial blood glucose levels, decreases HbA1c, increases insulin levels, restores the normal distribution of islet cells, and expands islet area in spontaneous type 2 diabetic db/db mice^[1].
WB403 (50-100 mg/kg; p.o.; single administration) significantly improves glucose tolerance and increases serum GLP-1 levels in normal ICR mice^[1].