Virtual screening and molecular dynamic simulation to identify the potent SOX2-inhibiting drugs

Abstract

Sex-determining region of Y-box2 (SOX2) is a master regulator of embryonic and induced pluripotent stem cells. SOX2 is also implicated in epithelial mesenchymal transition (EMT) and chemoresistance of cancer cells. Moreover, SOX2 has been described as a biomarker for cancer stem cells in cervical cancer, sarcoma, ovarian cancer, colorectal cancer, head and neck cancer and glioblastoma. The high expression of SOX2 is also negatively correlated with the overall survival of cancer patients which makes it an attractive target for cancer therapy. The current study was intended to identify SOX2 inhibitors with a high binding affinity. Structure based virtual screening was carried out on approved medications against SOX2 with the help of AutoDock VINA, which is included in the PyRx 0.8 package. The compound with the highest affinity was then examined, and structurally comparable compounds were docked to SOX2 protein once again in order to discover a new and more effective inhibitor molecule against SOX2. The docking analysis revealed apatinib as the most efficient anti-SOX2 drug among the known drug molecules. A structural derivative of apatinib, N-(4-Phenoxyphenyl)-2-[(Pyridin-4-ylmethyl) amino] nicotinamide, was identified as an even more effective inhibitor of SOX2 than apatinib.