In silico identification of potent small molecule inhibitors targeting epidermal growth factor receptor 1

摘要

Background: The receptor tyrosine kinase of the epidermal growth factor receptor (EGFR, ErbB) family played an important role in multisignaling pathways, which controlled numerous biological activities including proliferation, differentiation, apoptosis, etc. EGFR abnormalities have been associated with a variety of human tumors, which was a well-characterized target for cancer treatment. It was known to all that drug repositioning has been considered as a useful tool to accelerate the process of drug development. Materials and Methods: Herein, a total of 1408 small molecule drugs approved by the Food and Drug Administration (FDA) were employed to identify potential EGFR inhibitors by a series of bioinformatics approaches, including virtual screening and molecular dynamics (MD) simulations. Results: According to the docking score, five small molecules were chosed for further MD simulations. Following the 5 ns MD simulations, ZINC03830276 (Benzonatate) were finally recognized as “new use” of FDA-approved EGFR-targeting drug. Conclusions: Our findings suggested that the small molecule ZINC03830276 (Benzonatate) could be a promising EGFR inhibitor candidate and may also provide new ideas for designing more potent EGFR inhibitors for the future study.