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Updated: Jun 7, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Targeting adhesion G protein-coupled receptors. Current status and future perspectives
Fabian Liessmann1, Lukas von Bredow2, Jens Meiler3
1Institute for Drug Discovery, Medical Faculty, Leipzig University, 04103 Leipzig, Saxony, Germany; Center for Scalable Data Analytics and Artificial Intelligence, Leipzig University, 04105 Leipzig, Saxony, Germany.
None:
G protein-coupled receptors (GPCRs) orchestrate many physiological functions and are a crucial target in drug discovery. Adhesion GPCRs (aGPCRs), the second largest family within this superfamily, are promising yet underexplored targets for treating various diseases, including obesity, psychiatric disorders, and cancer. However, the receptors' unique and complex structure and miscellaneous interactions complicate comprehensive pharmacological studies. Despite recent progress in determining structures and elucidation of the activation mechanism, the function of many receptors remains to be determined. This review consolidates current knowledge on aGPCR ligands, focusing on small molecule orthosteric ligands and allosteric modulators identified for the ADGRGs subfamily (subfamily VIII), (GPR56/ADGRG1, GPR64/ADGRG2, GPR97/ADGRG3, GPR114/ADGRG5, GPR126/ADGRG6, and GPR128/ADGRG7). We discuss challenges in hit identification, target validation, and drug discovery, highlighting molecular compositions and recent structural breakthroughs. ADGRG ligands can offer new insights into aGPCR modulation and have significant potential for novel therapeutic interventions targeting various diseases.
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