Identification Of Inhibitors Targeting Hif-2 Alpha/C-Myc By Molecular Docking And Mm-Gbsa Technology

The treatment of ccRCC by targeting hypoxia-inducible factor HIF-2 alpha is currently a direct and effective method. Studies have shown that HIF-2 alpha and c-Myc cooperate to promote ccRCC tumor progression, and the overexpression of c-Myc is related to the progress and drug resistance of most human cancers. Although HIF-2 alpha and c-Myc are important drug targets, their dual inhibitors are still lacking. We used virtual screening tools (mainly including molecular docking and MM-GBSA technology) to obtain some well-listed compounds that can potentially target HIF-2 alpha and c-Myc and used molecular dynamics simulations to study their binding with these protein systems. Using a structure-based screening scheme, a batch of top-ranking compounds were selected, and their binding affinities were predicted of these compounds were performed. Representative compoundC93106,C43257, andC41580all showed good comprehensive binding score. Our results indicate that the target compounds can all form key interactions with the active site of the protein, and 30 nsmolecular dynamic simulation of the complex system indicates a stable binding conformation. This research laid the foundation for the development of more effective and specific HIF-2 alpha and c-Myc dual-target inhibitors.