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Updated: Dec 31, 2025

A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
Published on: December 2, 2022
Identification of novel GPR81 agonist lead series for target biology evaluation
Öjvind Davidsson1, Kristina Nilsson1, Jonas Brånalt1
1CVRM Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Abstract:
GPR81 is a novel drug target that is implicated in the control of glucose and lipid metabolism. The lack of potent GPR81 modulators suitable for in vivo studies has limited the pharmacological characterization of this lactate sensing receptor. We performed a high throughput screen (HTS) and identified a GPR81 agonist chemical series containing a central acyl urea scaffold linker. During SAR exploration two additional new series were evolved, one containing cyclic acyl urea bioisosteres and another a central amide bond. These three series provide different selectivity and physicochemical properties suitable for in-vivo studies.
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