%0 Journal Article %1 Liessmann2024 %A Liessmann, Fabian %A von Bredow, Lukas %A Meiler, Jens %A Liebscher, Ines, rahm %D 2024 %I Elsevier %J Structure %K ADGRG1 ADGRG2 ADGRG3 ADGRG5 ADGRG6 ADGRG7 GPCRs GPR114 GPR126 GPR128 GPR56 GPR64 GPR97 adhesion area_bigdata discovery drug ep ligands molecules small structure topic_lifescience xack yaff %R 10.1016/j.str.2024.10.022 %T Targeting adhesion G protein-coupled receptors. Current status and future perspectives %X 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.

@article{Liessmann2024, abstract = {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.}, added-at = {2024-11-28T13:27:37.000+0100}, author = {Liessmann, Fabian and von Bredow, Lukas and Meiler, Jens and {Liebscher, Ines}, rahm}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/20745798f0ce04bb24d60707bf5818f9d/scadsfct}, citation-subset = {IM}, country = {United States}, doi = {10.1016/j.str.2024.10.022}, interhash = {20a0f3684f103683451b6b8244a9f3d8}, intrahash = {0745798f0ce04bb24d60707bf5818f9d}, issn = {1878-4186}, issn-linking = {0969-2126}, journal = {Structure}, keywords = {ADGRG1 ADGRG2 ADGRG3 ADGRG5 ADGRG6 ADGRG7 GPCRs GPR114 GPR126 GPR128 GPR56 GPR64 GPR97 adhesion area_bigdata discovery drug ep ligands molecules small structure topic_lifescience xack yaff}, month = nov, nlm-id = {101087697}, owner = {NLM}, pii = {S0969-2126(24)00457-X}, pmid = {39520987}, publisher = {Elsevier}, pubmodel = {Print-Electronic}, pubstate = {aheadofprint}, revised = {2024-11-09}, timestamp = {2025-07-29T11:01:14.000+0200}, title = {Targeting adhesion G protein-coupled receptors. Current status and future perspectives}, year = 2024 }