Aryl-2-Thioxo-4-Thiazolidinones as HIF-2α Inhibitors

HIF-2α is a transcription factor that is activated under hypoxic conditions and promotes the expression of genes involved in angiogenesis. It plays crucial roles in the pathophysiological processes of various diseases, which indicates that targeting HIF-2α would be a valid approach for developing therapeutic agents for related diseases. In this study, a small chemical library, comprising various aryl-2-thioxo-4-thiazolidinone analogues, was screened for compounds with inhibitory activities against HIF-2α in cultured HTB94 cells. A chemical compound with an aryl-2-thioxo-4-thiazolidinone structure was found to exhibit considerable inhibitory activity. HRE and HIF-2α were introduced into the cells via transfection and adenoviral infection, respectively, and luciferase reporter gene assay was performed for each chemical compound in the library. Subsequently, three compounds were found to exhibit remarkable inhibitory activities against HIF-2α. The screened inhibitors represent effective tools for HIF-2α-related studies and may serve as drug candidates for related diseases.