Design and Discovery of Genistein-based Drugs as a Potential Tyrosine Kinase Inhibitor for Lung Adenocarcinoma through Hybrid In-silico Methods

Abstract

This research employs a comprehensive approach to investigate potential therapeutic candidates for lung adenocarcinoma through drug-drug transcriptomic similarity analysis and molecular docking simulations. Using the Connectivity Map Touchstone tool, we identified compounds with high transcriptomic similarity to genistein, revealing potential shared mechanisms of action. The selected compounds, including avrainvillamide-analog-2, were further assessed through molecular docking simulations against the tyrosine kinase inhibitor (TKI) enzyme. Avrainvillamide-analog-2 exhibited a remarkable binding affinity in pocket C2, interacting with key amino acids. The results provide valuable insights into the pharmacological properties of the identified compounds, laying the groundwork for future experimental validations and drug development initiatives. Additionally, cavities detection by CB Dock server and structural refinement by PDB REDO contribute to the overall understanding of ligand binding and protein structure. This integrative approach offers a holistic perspective for identifying potential lead compounds and understanding their molecular interactions, facilitating the rational design of novel therapeutics for lung adenocarcinoma.