Inhibitory Activities of 2-Arylbenzimidazole Analogues Targeting HIF-2α

HIF-2α is a transcription factor that plays a crucial role in angiogenesis. It is activated under hypoxic conditions and acts as a transcription factor. It has also been implicated in the pathogenesis of various diseases, establishing it as a promising target for the development of novel therapeutic agents for treating related diseases. In this study, a range of chemical compounds was evaluated for their ability to target HIF-2α in cultured HTB94 cells. A compound containing a 2-arylbenzimidazole structure was identified as an inhibitor. subsequently, a broader chemical library of 2-arylbenzimidazoles was synthesized and screened for their inhibitory activity. Genes encoding HRE and HIF-2α were introduced into cells by adenoviral infection and transfection, respectively. Luciferase activity was quantified in the presence of each compound. Two compounds demonstrated substantial HIF-2α inhibitory activity. These inhibitors are believed to serve as candidate compounds for the development of therapeutic agents to treat HIF-2 α-related diseases.