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چکیده
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Non-small cell lung cancer remains one of the leading causes of cancer-related mortality, with the epidermal growth factor receptor (EGFR T790M) mutation being a major mechanism of resistance to first- and second-generation tyrosine kinase inhibitors. In this study, the binding behavior of Baicalein, a naturally occurring flavonoid, toward EGFR T790M was systematically investigated and compared with the third-generation inhibitor Osimertinib using a comprehensive in silico approach. Molecular docking, molecular dynamics simulations, MM/PBSA binding free energy calculations, and ADMET predictions were performed. Docking analyses revealed stable interactions of Baicalein with key residues in the EGFR binding pocket, including MET793 and GLY796. Molecular dynamics simulations demonstrated the structural stability of the Baicalein-EGFR complex. Within the applied MM/PBSA framework, Baicalein exhibited a more favorable binding free energy (−43.35 ± 13.56 kJ/mol) than Osimertinib (−30.71 ± 14.14 kJ/mol). In silico ADMET profiling suggested favorable pharmacokinetic and safety-related properties for Baicalein. Overall, these findings highlight Baicalein as a promising natural scaffold for further exploration in the context of EGFR T790M inhibition.
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