Akademik Veri Yönetim Sistemi
International Multidisciplinary Symposium on Drug Research and Development - DRD 2023, İzmir, Türkiye, 4 - 06 Mayıs 2023, ss.112
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 (e.g., Alzheimer's disease)
and are collectively referred to as "tauopathies". The most notable kinase identified in tau
phosphorylation is glycogen synthase kinase 3 (GSK3). 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 (e.g., HIT 2.0, PubChem, and ChEMBL) were
searched for potential inhibitory drugs against GSK-3β and found 58 drugs. The drugs were
filtered according to physicochemical-pharmacological properties and toxicity profiles via
SwissADME, ADMETlab 2.0, pkCSM, and ProTox-II, free web tools. After pre-filtration,
molecular docking was performed against GSK-3β (PDB ID: 5K5N) 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) (Table 1)
against GSK-3β among the seven drugs [compared to PF-04802367 (PDB ID: 6QH), a highly
selective brain-penetrant kinase inhibitor]. Nabumetone is an NSAID used to treat some
arthritis, postoperative pains, and dysmenorrhea. Our results suggest that nabumetone may
be a potential inhibitor of GSK-3β.