1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Discovery of new natural inhibitors for Human epidermal growth factor receptor-2 (HER2) for treating Breast cancer disease
Paper ID : 1163-ICB10
Authors:
Sina Mohammad Mehri *1, Samad Nejad Ebrahimi2
1پژوهشکده گیاهان و مواد اولیه دارویی دانشگاه شهیدبهشتی تهران
2عضو هیئت علمی رشته فیتوشیمی پژوهشکده گیاهان و مواد اولیه دارویی دانشگاه شهیدبهشتی تهران
Abstract:
Background and Aim: Breast cancer is one of the most common diseases among women that is directly related to epidermal growth factor (EGF). Human epidermal growth factor receptor-2 (HER2) is a component of the tyrosine kinase family, which is overexpressed in this disease and its exacerbation and overexpression cause the proliferation and metabolism of breast cancer cells [1]. In recent years, attempts have been made to use small molecules such as HER2 inhibitor molecules instead of chemotherapy to inhibit the overgrowth of cancer cells and to treat breast cancer [2]
Methods: Virtual screening based on docking studies was performed using the Glide and Induced fit docking (IFD) program in Maestro 12.8 (Schrodinger, LLC). More than 700 natural compounds were downloaded from the Zinc database and prepared with Ligprep software. Protein was obtained from the protein database (PDB ID: 3PP0) and prepared using protein preparation software. QSAR and Qikprop studies also were performed to evaluate the IC50 and Lipinski data for the selected compounds.
Results: The results of molecular binding in XP and IFD studies determined the Nu.1 ligand (Zinc ID 253502387) with a docking score -10.207 kcal/mol, IFD score -1281.20 kcal/mol and calculated IC50 5.255 µM as a potent inhibitory compound for HER2. The NL2 with CID: 16736274 was considered as a native ligand with a docking score of -4.561 Kcal/mol and an IFD score of -1271.87 Kcal/mol and Calculated an IC50 5.273 µM with the enzyme. The obtained results show a high inhibitory activity of the selected compound compared to the native ligand.
Conclusion: According to the mentioned data Ligand with Zinc ID 253502387 was selected as a potent natural inhibitor for the HER2 compared to the native ligand. This Natural ligand helps to better inhibit the HER2 and stop cell growth and proliferation
Keywords:
Epidermal growth factor (EGF), HER2 receptor, Breast cancer, small molecules
Status : Paper Accepted (Poster Presentation)