sitagliptin-phosphate and imidazole

TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes.

Topics: Animals; Binding Sites; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Half-Life; Humans; Hypoglycemic Agents; Imidazoles; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Protein Structure, Tertiary; Receptors, G-Protein-Coupled; Sitagliptin Phosphate; Structure-Activity Relationship