Zingerone as a Promising Natural Inhibitor of EGFR in Breast Cancer: Integrative Approaches Combining Network Pharmacology, Molecular Docking, Dynamics Simulation, DFT, and ADMET Profiling

ABSTRACT Breast cancer (BC) is the leading cause of mortality from malignancy in women, and a definitive cure is still sought. Therefore, it is imperative to develop effective therapies to combat this deadly disease. This research addresses this need by through comprehensive network pharmacology and in silico approaches to investigate the anticancer activity of zingerone. The top 10 drug‐disease associated gene targets were identified based on GO and KEGG analyses. Epidermal growth factor receptor (EGFR) was considered a core gene associated with BC using PPI mapping. The EGFR‐ZinG complex exhibited the strongest affinity, with a molecular docking score of −6.4 kcal/mol. Further analysis of the pharmacokinetic properties indicated that ZinG did not breach the Lipinski Rule of Five, confirming its drug‐like properties. The clinical relevance of the core targets was assessed using the GEPIA, HPA, TIMER, and cBioPortal databases. MD simulation during a 100 ns period, coupled with the determination of RMSD, RMSF, and R g, indicated steady complex formation. Principal component analysis also revealed that the ZinG‐EGFR complex formed a tight structure. Overall, these findings suggest that ZinG may be a promising drug candidate for BC by targeting an EGFR‐centric signaling pathway and warrant further clinical research.