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Updated: Mar 26, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist
Sameer Agarwal1, Amit Patil1, Umesh Aware1
1Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India.
Abstract:
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 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/kg.
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