In Silico Screening of the MolPort Natural Product Database to Identify Potential Lyn Tyrosine Kinase Inhibitors for the Treatment of Triple-Negative Breast Cancer

Triple-Negative Breast Cancer (TNBC) poses a significant global health challenge due to its aggressive clinical behavior, high recurrence rates, and the limited effectiveness of available therapeutic options. This study aims to identify bioactive Natural compounds with potential inhibitory effects against Lyn tyrosine kinase, a key enzyme implicated in the pathogenesis of TNBC. Online servers including Molport, Permit, SWISSADME, and ProTox-iii were employed to screen the compounds. Ten thousand natural bioactive compounds were successfully retrieved from the Molport Natural Compound Database. Compounds were screened for structural similarity to the co-crystallized ligand (Dasatinib), toxicity, and ADME properties, after which 68 compounds were selected for further studies. Docking was performed using AutoDock Vina, and Molecular Dynamics simulations were performed using GROMACS 2026.2. Docking studies showed binding energy values ranging from -6.9 to -9.7 kcal/mol, comparable to the co-crystallized ligand, which had a binding affinity of -9.7 kcal/mol. The most notable interactions are ASP329, LEU275, LYS253, GLU290, MET322, and THR319, which interact via pi-cation and van der Waals interactions. Lig28 interacted with key amino acid residues, including LEU253, MET322, LYS275, and THR319, via pi-alkyl, pi-cation, and van der Waals interactions. ADMET profiling and docking results further prioritized the Lig28 molecule. Molecular dynamics simulations confirmed its potent predicted inhibitory activity and complex stability against the target. These findings highlight the potential of these identified compounds as promising Lyn Kinase inhibitors for TNBC therapy, offering a strategic avenue to combat resistance mechanisms. Further experimental validation is warranted to translate these computational insights into therapeutic candidates.