Discovery of new natural inhibitors for Human epidermal growth factor receptor-۲ (HER۲) for treating Breast cancer disease

Background and Aim: Breast cancer is one of the most common diseases among women that is directlyrelated to epidermal growth factor (EGF). Human epidermal growth factor receptor-۲ (HER۲) is a componentof the tyrosine kinase family, which is overexpressed in this disease and its exacerbation and overexpressioncause the proliferation and metabolism of breast cancer cells. In recent years, attempts have been made touse small molecules such as HER۲ inhibitor molecules instead of chemotherapy to inhibit the overgrowth ofcancer cells and to treat breast cancer.Methods: Virtual screening based on docking studies was performed using the Glide and Induced fit docking(IFD) program in Maestro ۱۲.۸ (Schrodinger, LLC). More than ۷۰۰ natural compounds were downloadedfrom the Zinc database and prepared with Ligprep software. Protein was obtained from the protein database(PDB ID: ۳PP۰) and prepared using protein preparation software. QSAR and Qikprop studies also wereperformed to evaluate the IC۵۰ and Lipinski data for the selected compounds.Results: The results of molecular binding in XP and IFD studies determined the Nu.۱ ligand (Zinc ID۲۵۳۵۰۲۳۸۷) with a docking score -۱۰.۲۰۷ kcal/mol, IFD score -۱۲۸۱.۲۰ kcal/mol and calculated IC۵۰ ۵.۲۵۵μM as a potent inhibitory compound for HER۲. The NL۲ with CID: ۱۶۷۳۶۲۷۴ was considered as a nativeligand with a docking score of -۴.۵۶۱ Kcal/mol and an IFD score of -۱۲۷۱.۸۷ Kcal/mol and Calculated anIC۵۰ ۵.۲۷۳ μM with the enzyme. The obtained results show a high inhibitory activity of the selectedcompound compared to the native ligand.Conclusion: According to the mentioned data Ligand with Zinc ID ۲۵۳۵۰۲۳۸۷ was selected as a potentnatural inhibitor for the HER۲ compared to the native ligand. This Natural ligand helps to better inhibit theHER۲ and stop cell growth and proliferation.

Keywords:

Epidermal growth factor (EGF) , HER۲ receptor , Breast cancer , small molecules