همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Investigating the role of ursolic acid in EGFR L858R mutant inhibition in non-small cell lung cancer: Molecular docking and ADMET prediction

نویسندگان :

Tooba Abdizadeh¹

1- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

کلمات کلیدی :

EGFR L858R mutant،Ursolic acid،Molecular docking،ADMET

چکیده :

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 (Saini and Grewal, 2022). Mutations such as L858R, T790M, G719S, T790M/L858R or G719S/T790M 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 (Gao and Chen, 2024; García-Godoy and López-Camacho, 2016). 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 L858R mutant kinase domain (PDB ID; 2EB3) was retrieved from the RCSB PDB database and Ursolic acid and erlotinib were obtained Pubchem and converted into PDB format by Chem 3D 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 Lys745 and Cys797 and van der Waals interactions with Ala722, Leu718, and Leu844 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.