Akademik Veri Yönetim Sistemi
Hacettepe University Journal of the Faculty of Pharmacy, cilt.2024, sa.Special Issue, ss.11-16, 2024 (Scopus)
Tau, a protein associated with microtubules, is widely distributed throughout the central nervous system and promotes the polymerization, assembly, and stability of microtubules. Hyperphosphorylation of tau proteins leads to intracellular neurofibrillary tangles, which are the pathological hallmark of numerous neurodegenerative diseases and are collectively referred to as “tauopathies”. The most notable kinase identified in tau phosphorylation is glycogen synthase kinase 3 (GSK-3). Among the GSK-3 isoforms, GSK-3β has been linked to the pathophysiology of neurodegenerative diseases. Pharmacological inhibition of GSK-3β has been suggested as a potential therapeutic target for these diseases. In this study, the literature and databases were searched for potential inhibitory drugs against GSK-3β and 58 drugs were found. The drugs were filtered according to physicochemical-pharmacological properties and toxicity profiles via SwissADME, pkCSM, and ProTox-II, free web tools. After prefiltration, molecular docking was performed against GSK-3β with the remaining seven drugs (Nabumeton, Loxoprofen, Ketoprofen, Oxytetracycline, Benzoyl Peroxide, Naproxen, and Epinephrine Hydrochloride). According to the results, nabumetone had the best binding energy (-7.39 kcal/mol) and inhibition ability at the lowest concentration (3.8 µM) against GSK-3β among the seven drugs [compared to PF-04802367, a highly selective brain-penetrant kinase inhibitor]. Our results suggest that nabumetone may be a potential inhibitor of GSK-3β.