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Updated: Feb 22, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration
Steven M Sparks1, Paul K Spearing1, Caroline J Diaz1
1Enteroendocrine Discovery Performance Unit and Platform Technologies and Science, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
Abstract:
Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774).
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