Discovery of promising inhibitors for VEGFR-2 using computational methods

Abstract

VEGFR-2 (vascular endothelial growth factor receptor 2) is widely acknowledged as a highly effective target for the advancement of tumor treatment based on angiogenesis. The growth of tumors, their spread to other parts of the body, and their resistance to many drugs are strongly influenced by the formation of new blood vessels (angiogenesis) and the identification of small compounds that can target VEGFR-2. The potential ability of these molecules to inhibit angiogenesis is of great interest to researchers studying anti-cancer treatments. Several small molecule inhibitors targeting VEGFR-2 have received approval for treating various types of malignancies. One of the most recent updates is tivozanib, which has been approved by the FDA specifically for treating relapsed or refractory advanced renal cell carcinoma (RCC). Nevertheless, the inherent and acquired resistance of the protein, toxicity of compounds, and extensive array of adverse effects continue to be significant concerns. These factors contribute to the limited duration of clinical effectiveness and the ineffectiveness of antiangiogenic medications. We utilized a blend of computational techniques and strategies for the purpose of identifying new, promising, and small molecule inhibitors of VEGFR-2. Our aim was to find alternatives to the chemical structures and components of the existing inhibitors. The present research aimed to employ several sophisticated computer-aided procedures and approaches in the field of drug design and discovery. The techniques employed encompassed ligand- and structure-based virtual screening, estimation of binding free energy, and study of RMSD (Root Mean Square Deviation). The aim is to identify new promising small molecules that may effectively bind to VEGFR-2 and possess the capability to hinder the process of angiogenesis. Five indole derivatives were designed. According to docking study outcomes, these derivatives could be considered as notable candidates as VEGFR-2 inhibitors.