Description
Tideglusib (NP031112, NP-12) is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Phase 1/2.
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Molecular Formula
C19H14N2O2S
Chemical Name
1,2,4-Thiadiazolidine-3,5-dione, 2-(1-naphthalenyl)-4-(phenylmethyl)-
Solubility
DMSO 1 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
Tideglusib irreversibly inhibits GSK-3, reduces tau phosphorylation, and prevents apoptotic death in human neuroblastoma cells and murineprimary neurons. 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.
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.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.
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