In Silico Study of Licorice (Glycyrrhiza inflata) Compounds on EGFR Inhibition as an Anti-Lung Cancer Agent
Abstract
Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide, with wild-type epidermal growth factor receptor (wild-type EGFR) being an important therapeutic target. This study aimed to identify potential wild-type EGFR inhibitors from Glycyrrhiza inflata through an in silico approach. A total of 184 phytochemicals were sequentially evaluated using Lipinski's Rule of Five, ADMET prediction, pharmacophore-based virtual screening, and molecular docking against the wild-type EGFR kinase domain (PDB ID: 3POZ). The docking protocol was validated by redocking the native ligand (TAK-285), yielding a root mean square deviation (RMSD) of 1.27 Å, indicating reliable docking performance. Drug-likeness and ADMET screening identified 61 compounds with favorable physicochemical, pharmacokinetic, and safety profiles for subsequent analyses. Compared with the reference inhibitor erlotinib, Parvisoflavone A exhibited a lower binding affinity (−8.91 kcal/mol; Ki=292.70 nM vs. −9.66 kcal/mol; Ki=83.43 nM), but demonstrated the highest pharmacophore fit score (42.63%), favorable drug-likeness and ADMET properties, and interactions with the key catalytic residues Lys745, Asp855, and Thr790 within the ATP-binding pocket of wild-type EGFR. These findings identify Parvisoflavone A as a promising hit compound for wild-type EGFR inhibition and provide a basis for further molecular dynamics simulations and experimental validation for NSCLC.
Keywords: Glycyrrhiza inflata, molecular docking, non-small cell lung cancer, pharmacophore modeling, wild-type EGFR.
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DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev16iss3pp242-258
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