{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:16:04Z","timestamp":1777396564943,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,11,7]]},"abstract":"<jats:p>Background: Tyrosine-protein kinase Fyn (Fyn) is a critical signaling molecule involved in various cellular processes, including neuronal development, synaptic plasticity, and disease pathogenesis. Dysregulation of Fyn kinase has been implicated in various complex diseases, including neurodegenerative disorders such as Alzheimer\u2019s and Parkinson\u2019s diseases, as well as different cancer types. Therefore, identifying small molecule inhibitors that can inhibit Fyn activity holds substantial significance in drug discovery. Objective: The aim of this study was to identify potential small-molecule inhibitors among bioactive phytoconstituents against tyrosine-protein kinase Fyn. Methods: Through a comprehensive approach involving molecular docking, drug likeliness filters, and molecular dynamics (MD) simulations, we performed a virtual screening of a natural compounds library. This methodology aimed to pinpoint compounds potentially interacting with Fyn kinase and inhibiting its activity. Results: This study finds two potential natural compounds: Dehydromillettone and Tanshinone B. These compoundsdemonstrated substantial affinity and specific interactions towards the Fyn binding pocket. Their conformations exhibitedcompatibility and stability, indicating the formation of robust protein-ligand complexes. A significant array of non-covalentinteractions supported the structural integrity of these complexes. Conclusion: Dehydromillettone and Tanshinone B emerge as promising candidates, poised for further optimization as Fynkinase inhibitors with therapeutic applications. In a broader context, this study demonstrates the potential of computationaldrug discovery, underscoring its utility in identifying compounds with clinical significance. The identified inhibitors holdpromise in addressing a spectrum of cancer and neurodegenerative disorders. However, their efficacy and safety necessitatevalidation through subsequent experimental studies.<\/jats:p>","DOI":"10.3233\/jad-230828","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T11:23:29Z","timestamp":1698405809000},"page":"827-844","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling Phytoconstituents with Inhibitory Potential Against Tyrosine-Protein Kinase Fyn: A Comprehensive Virtual Screening Approach Targeting Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"96","author":[{"given":"Mohammed","family":"Alrouji","sequence":"first","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taghreed A.","family":"Majrashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Khalid University (KKU), Guraiger, Abha, Saudi 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