Dasatinib as a Repurposing Candidate for Alzheimer’s Disease: An Integrated In Silico Network Pharmacology and Molecular Docking Study

Abstract

Background: Alzheimer’s disease (AD) lacks broadly effective disease-modifying therapy, and repeated failure of single-target approaches has increased interest in multi-target drug repurposing strategies. Fyn kinase (FYN) is a mechanistic node in the amyloid-β–tau–Fyn pathogenic axis, and dasatinib is an approved multi-kinase inhibitor with potent Src-family activity and preliminary evidence of central nervous system exposure in AD-related studies. The present study aimed to systematically evaluate dasatinib as an AD repurposing candidate through an integrated in silico network pharmacology and molecular docking workflow.

Methods: An integrated in silico workflow was applied using SwissTargetPrediction-based human target prediction, GeneCards disease-gene mining, STRING/Cytoscape protein-protein interaction (PPI) network analysis with degree-centrality hub prioritization, STRING functional enrichment, and CB-Dock2/AutoDock Vina blind molecular docking to the human FYN domain (protein data bank: 2DQ7). Fyn kinase was selected as the docking target based on pre-specified criteria combining AD-specific mechanistic evidence, prior clinical precedent, and top-5 hub ranking.

Results: SwissTargetPrediction identified 100 putative human targets for dasatinib, whereas GeneCards returned 13 890 AD-associated genes; intersection analysis yielded 83 overlapping targets. Degree-centrality analysis ranked epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), SRC proto-oncogene non-receptor tyrosine kinase (SRC), ABL proto-oncogene 1 non- receptor tyrosine kinase (ABL1), and Fyn kinase (FYN) as the 5 highest-degree hub nodes. Mitogen-activated protein kinase (MAPK) signaling was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, followed by PI3K-Akt signaling and axon guidance, while protein kinase activity was the dominant gene ontology (GO) molecular function term. Blind docking suggested plausible accommodation of dasatinib in the Fyn ATP-binding pocket, with a best AutoDock Vina score of −9.7 kcal/mol and substantial residue-level overlap with the reference compound saracatinib.

Conclusion: Integrated network pharmacology, functional enrichment, and molecular docking support dasatinib as a hypothesis-generating AD repurposing candidate with convergence on Fyn-centered kinase signaling. These findings remain computational and require staged biochemical, pharmacokinetic, cellular, and in vivo validation.

Cite this article as: Küçük Yılmaz N. Dasatinib as a repurposing candidate for Alzheimer’s disease: an integrated in silico network pharmacology and molecular docking study. Trends Pharm. 2026, 3, 0015, doi: 10.5152/TIP.2026.26015.