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Probe and Assay Dependent Pharmacology of Dantrolene Analogues at the GPR35
Yaopeng Zhao1,2, Jingmin Cui1, Hui Wen2
1State Key Lab of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Abstract:
The G-protein-coupled receptor 35 (GPR35) plays a key role in various physiological and pathological processes and has emerged as a potential therapeutic target for the treatment of pain, inflammation, and metabolic diseases. Herein, we report the discovery and characterization of dantrolene analogues as GPR35 ligands. Pharmacological profiling with label-free dynamic mass redistribution and Tango arrestin assays showed that the 2,4-imidazolidinedione-containing analogues of dantrolene act as partial agonists of the GPR35, while its urea, thiourea, or amido derivatives display probe and assay dependent antagonism against the receptor.
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