Molecular Docking Comparison of Icotinib and Erlotinib as EGFR Inhibitors

Abstract

Background: Epidermal growth factor receptor (EGFR) is a key tyrosine kinase receptor that regulates cell growth and survival by activating intracellular signaling pathways. Activating mutations in EGFR are involved in the development of cancers such as lung, pancreatic, and colorectal cancers by causing uncontrolled proliferation and inhibiting apoptosis. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been introduced as targeted drugs, a new approach in the treatment of these cancers. Erlotinib, an EGFR-TKI approved by the U.S. Food and Drug Administration (FDA), has been widely used in the treatment of patients with EGFR mutations since 2004. A similar EGFR-TKI developed in China, icotinib, has not yet received FDA approval. Objectives: The present study aimed to compare the binding interactions and affinities of two EGFR tyrosine kinase inhibitors, erlotinib and icotinib, to the EGFR using the molecular docking technique, to evaluate the potential effectiveness of icotinib as a targeted cancer therapy. Methods: Auto Dock Tool and Discovery Studio 4.5 software were used to prepare ligands and receptors. Molecular docking was performed using AutoDock Vina, and visualization of molecular interactions was performed using LigPlot+ software. Results: The results of this study showed that both ligands bound to EGFR through hydrogen bonding with methionine 769. Additionally, the results of molecular docking showed that the binding energy of icotinib with EGFR is -8.7 kcal/mol, and the binding energy of erlotinib with EGFR is -7.3 kcal/mol. Conclusions: Given these results, it can be expected that in the future, by conducting more experimental and clinical phases, icotinib will be approved by the FDA and used as a more effective drug in the treatment of cancers with mutations in EGFR.