Year: 2025 | Month: December | Volume: 12 | Issue: 12 | Pages: 739-751
DOI: https://doi.org/10.52403/ijrr.20251276
Molecular Docking of Fangchinoline against Bruton’s Tyrosine Kinase (BTK) as a Potential Anticancer Target
Alan Maulana1, Poppy Anjelisa Zaitun Hasibuan2, Denny Satria3
1Master in Pharmaceutical Sciences Program, 2Departement of Pharmacology, 3Department of Pharmaceutical Biology,
Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia.
Corresponding Author: Poppy Anjelisa Zaitun Hasibuan
ABSTRACT
Bruton’s tyrosine kinase is an oncogenic kinase implicated in B-cell malignancies, and fangchinoline is a natural alkaloid with reported anticancer properties. This study evaluated the binding of fangchinoline to Bruton’s tyrosine kinase using structure-based docking. The Bruton’s tyrosine kinase protein structure (PDB ID 3GEN) was prepared by removing water molecules and existing ligands, and docking simulations were performed using the AutoDock Tools. Fangchinoline bound to the adenosine triphosphate-binding pocket with a predicted binding free energy of –8.56 kcal/mol. In the optimal binding pose, fangchinoline formed hydrogen bonds with Ser538 and Asp539 in the kinase activation loop and hydrophobic contacts with residues including Cys481, Lys430, Leu408, Val416, Ala428, and Leu528. The compound bound to the ATP site in a non-covalent manner, using the activation loop and hydrophobic pocket residues. Overall, the docking results indicated that fangchinoline could serve as a candidate for further investigation as a BTK-targeted anticancer agent.
Keywords: Fangchinoline; Bruton’s tyrosine kinase; Molecular docking; Cancer therapy; Natural Product; Binding affinity
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