Investigating the role of ursolic acid in EGFR L۸۵۸R mutant inhibition in non-small cell lung cancer: Molecular docking and ADMET prediction

One of the leading causes of cancer deaths worldwide is lung cancer. Human epidermal growth factor (EGFR), a target protein for the treatment of non-small cell lung cancer (NSCLC), plays a critical role in signaling pathways such as cell proliferation and migration. Mutations such as L۸۵۸R, T۷۹۰M, G۷۱۹S, T۷۹۰M/L۸۵۸R or G۷۱۹S/T۷۹۰M can alter its structure and consequently the drug responses of lung cancer patients. Therefore, in silico studies are essential to understand how these mutations affect the ligand binding site. In this study, in silico molecular docking was performed using AutoDock Vina by PyRx software for ursolic acid as a triterpenoide and erlotinib as a reference against EGFR. The crystal structure of EGFR L۸۵۸R mutant kinase domain (PDB ID; ۲EB۳) was retrieved from the RCSB PDB database and Ursolic acid and erlotinib were obtained Pubchem and converted into PDB format by Chem ۳D software. Also, Physicochemical properties and pharmacokinetics parameters were assessed by Lipinski rule of five and ADMET-based analysis. The docking results obtained showed the strong binding affinity of ursolic acid with EGFR and the most important hydrogen interactions are Lys۷۴۵ and Cys۷۹۷ and van der Waals interactions with Ala۷۲۲, Leu۷۱۸, and Leu۸۴۴ amino acids. The drug-likeness and pharmacokinetic properties of ursolic acid also displayed drug-like characteristics. Ursolic acid could be a potential source of natural products that have inhibitory effects on lung cancer by blocking the EGFR mutated protein. Further, the experimental investigation of the ursolic acid is a must before any prescription.

کلیدواژه ها:

EGFR L۸۵۸R mutant ، ursolic acid ، molecular docking ، ADMET