Identification of 3-aryl-5-methyl-isoxazole-4-carboxamide derivatives and analogs as novel HIF-2α agonists through docking-based virtual screening and structural modification
erythropoietin (EPO) production. A docking-based virtual screening on crystal structures of HIF-2α inhibitors unexpectedly identified 3-phenyl-5-methyl-isoxazole-4-carboxamide derivative as a hit of HIF-2α agonist. Further structural optimizations of compound led to the discovery of a series of HIF-2α agonists with novel scaffolds. The most promising compounds and exhibited potent HIF-2α agonistic activities