Virtual Screening of EGFR Inhibitors for Cancer Treatment

EGFRs are a big family of tyrosin kinase receptors involved in many cancers such as breast, lung, esophageal,head, and neck. EGFR and its family contribute to a signaling cascade regulating cancer cells’ growth,differentiation, adhesion, migration, and survival. The Binding of ligands such as TGF and EGF to theextracellular domain of EGFR induces tyrosin kinase domain dimerization and initiates tumor formation.EGFR is overexpressed in some human cancers and is considered a promising target for new anticancerdrugs. Erlotinib is a common inhibitor of EGFR that blocks its function by binding to the intracellular tyrosinekinase domain and restricts downstream signaling pathway leading to cancer.In this project, we used virtual screening method by using molecular docking. For this purpose, we usederlotinib as a query for similarity search to make a library of compounds. We filtred them by Lipinski’s roleof five filters. Then, high-throughput docking software “PyRx” was used for molecular docking of thesecompounds with EGFR. Finally, the results of docking were analyzed by “Lig Plot” software.Results show that of the ۱۳۵ compounds obtained from similarity search, the compound with pubchemCID=۱۰۴۰۴۹۲۲۷۷ has the most significant binding energy(ΔG=-۱۲.۷). This compound can be considered apotential inhibitor of EGFR that has more significant energy binding than erlotinib and can be used in furtherinvestigation.

کلیدواژه ها:

cancer ، EGFR ، molecular docking ، virtual screening ، signaling pathway