Related Experiment Video
Updated: Oct 25, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Development of Potent G Protein Pathway-Biased GPR183 Agonists
Kaustubh R Bhuskute1, Asmita Manandhar1, Viktoria M S Kjær2
1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, 2100Copenhagen, Denmark.
Abstract:
GPR183 is an oxysterol-sensing GPCR predominantly expressed in lymphoid organs and tissues. Activation of the receptor by oxysterol 7α,25-OHC leads to Gαi protein-mediated signaling as well as β-arrestin2 recruitment. GPR183/oxysterol signaling modulates localization of lymphoid cells; consequently, the receptor is associated with several inflammation-associated diseases and is an interesting potential drug target. Previously, we reported the discovery of moderately potent G protein-biased partial agonists for GPR183 from a virtual screening based on the antagonist NIBR189. Herein, we present the detailed structure-activity investigations and optimizations, which led to the identification of full agonists for GPR183 with complete bias for G protein signaling and low nanomolar potency, including 63 (TUG-2604) with potency and efficacy similar to 7α,25-OHC. Notably, 63 was unable to induce migration of human dendritic cells but inhibited migration induced by 7α,25-OHC. This compound will be valuable for further explorations of the signaling-specific function and drug target potential of GPR183.
Related Concept Videos
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs Regulate Adenylyl Cylase Activity
Two...
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical, 7TM, or...
Activation and Inactivation of G Proteins
GPCR Desensitization

