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GPR35 is a family A orphan G protein-coupled receptor whose biological functions are largely unknown. Identification of novel GPR35 ligands is essential to elucidate the biology and pathophysiology of GPR35. Here we report the discovery of nitrophenol compounds to be a novel chemical class of GPR35 agonists. Both endogenously and stably expressed GPR35 were found to be activated by a number of nitrophenol analogues including 2-amino-4,6-dinitrophenol, tolcapone and nitecapone. Among them, 4,4′-(2,2-dichloroethene-1,1-diyl)bis(2,6-dinitrophenol) was found to be the most potent GPR35 agonist.
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