Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative <b>6g</b> was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC₅₀ = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound <b>6g</b> was found to have potent glucose lowering effects <i>in vivo</i> during an oral glucose tolerance test in DIO C57 mice with ED₅₀ of 7.9 mg/kg and ED₉₀ of 29.2 mg/kg

Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative <b>6g</b> was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC₅₀ = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound <b>6g</b> was found to have potent glucose lowering effects <i>in vivo</i> during an oral glucose tolerance test in DIO C57 mice with ED₅₀ of 7.9 mg/kg and ED₉₀ of 29.2 mg/kg