Vikash Jakhmola, Tarun Parashar, Pallavi Ghildiyal, A.N.M. Ansori, Rajeev Kumar Sharma, N.G. Raghavendra Rao, Kapil Kalra, Nishan Singh, Nidhi Nainwal, Rajeev Kumar Singh, M.P. Singh, Vishwadeepak Kimothi, Alok Bhatt, Ashish Dimri, Ravi Kumar, Amit Semwal, Nur Sofiatul Aini, Maksim Rebezov
EGFR is a tyrosine kinase receptor that has a role in the tumorigenesis of many types of solid tumors. Aberrantly phosphorylated or overexpressed EGFR is associated with cellular proliferation, prevention of apoptosis, activation of invasion and metastasis, and stimulation of tumor-induced neovascularization. EGFR’s hyperactivity has been observed in ovarian cancer. Although conventional chemotherapy and surgery for advanced ovarian cancer have improved over the years, still there is a critical need for the development of molecular targeted therapies. The major challenge for this approach is the complete understanding of the protein structure of this mega receptor. In this study, we explored this receptor using in silico tools. The protein structure of the EGFR kinase domain (PDB ID: 1M17) and co-crystal containing EGFR and PTP1B kinase domain fragment (PDB ID: 3I7Z) were obtained from the RCSB Protein Data Bank. We performed protein-protein docking using BioLuminate. It was found in this study that the DADEYL segment of EGFR (position 988-993) which includes autophosphorylated tyrosine at position 992, is the segment that is responsible for the overexpression of this receptor in ovarian cancer. There are currently two main classes of clinically-approved drugs which downregulate EGFR activity; tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (Mabs). However, treatment with both type of therapies has been met with shortcomings. Therefore, there is a need for further studies to explore the suitable ligands that can downregulate its activity. © 2022 Phcogj.Com. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India; Nidom Foundation, Surabaya, Indonesia; School of Pharmaceutical and Population Health Informatics, DIT University, India; Kiet School Of Pharmacy, Kiet Group Of Institutions. Delhi-Ncr, Meerut Road, Uttar Pradesh, Ghaziabad, 201206, India; Alpine College of Management and Technology, Uttarakhand, Dehradun, India; Srajan Institute of Pharmacy, Uttar Pradesh, Lakhimpur Kheri, India; Apex Institute of Pharmacy, Samaspur, Mirzapur Uttar Pradesh, Chunar, India; School of Agriculture, Uttaranchal University, Uttarakhand, Dehradun, India; Himalayan Institute of Pharmacy and Research, Uttarakhand, Dehradun, India; School of Pharmaceutical Sciences, Himgiri Zee University, Uttarakhand, Dehradun, India; GRD(PG) IMT Dehradun, Uttarakhand, India; Faculty of Mathematics and Natural Sciences, State University of Surabaya, Surabaya, Indonesia; Department of Scientific Research, Russian State Agrarian University, Moscow Timiryazev Agricultural Academy, Moscow, Russian Federation; Faculty of Biotechnology and Food Engineering, Ural State Agrarian University, Yekaterinburg, Russian Federation; Department of Scientific Research, K.G. Razumovsky Moscow State University of Technologies and Management, The First Cossack University, Moscow, Russian Federation
