Tideglusib的生物活性

Tideglusib(NP-031112) is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM.
IC50 value: 60 nM [1]
Target: GSK-3β
in vitro: Tideglusib irreversibly inhibits GSK-3, reduces tau phosphorylation, and prevents apoptotic death in human neuroblastoma cells and murineprimary neurons [1]. Tideglusib (2.5 μM) inhibits glutamate-induced glial activation as evidenced by decreased TNF-α and COX-2 expression in rat primary astrocyte or microglial cultures. Tideglusib (2.5 μM) also exerts a potent neuroprotective effect on cortical neurons from glutamate-induced excitotoxicity as evidenced by significant reduction in the number of Annexin-V-positive cells in rat primary astrocyte or microglial cultures [2].
in vivo: Tideglusib (50 mg/kg) injected into the adult male Wistar rats hippocampus dramatically reduces kainic acid-induced inflammation and has a neuroprotective effect in the damaged areas of the hippocampus [2]. Tideglusib (200 mg/kg, oral) results in lower levels of tau phosphorylation, decreased amyloid deposition and plaque-associated astrocytic proliferation, protection of neurons in the entorhinal cortex and CA1 hippocampal subfield against cell death, and prevention of memory deficits in APP/tau double transgenic mice [3].

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相關(guān)文獻(xiàn)

[1]. Domínguez JM, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem, 2012, 287(2), 893-90

[2]. Luna-Medina R, et al. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci, 2007, 27(21), 5766-5776.

[3]. Sereno L, et al. A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009 Sep;35(3):359-67