Tideglusib | CAS:865854-05-3

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Name:Tideglusib; NP-12; NP031112
Cat. No. :CS-0613
CAS No. :865854-05-3
Formula:C19H14N2O2S
M. Wt. : 334.39
Solubility:DMSO: 12.5 mg/mL

Tideglusib is an irreversible GSK-3 inhibitor with IC50 of 5 nM and 60 nM for GSK-3βWT (1 h preincubation) and GSK-3βC199A (1 h preincubation), respectively.IC50 & Target: IC50: 5 nM (GSK-3βWT), 60 nM (GSK-3βC199A)[1]In Vitro: Tideglusib (NP12) is a small heterocyclic thiadiazolidinone (TDZD) derivative, which is an ATP-non competitive inhibitor of GSK-3β with an IC50 value in the micromolar range[2]. Incubation of both astrocyte and microglial cultures with Tideglusib (NP031112) completely abrogates the induction of TNF-α and COX-2 expression after glutamate treatment. These effects of NP031112 are not caused by a loss of cell viability, because the 24 h exposure of astrocyte and microglial cells to this TDZD does not modify cell viability[3].In Vivo: Tideglusib (NP12) treatment correlates with an increase of 46% as an average in the inhibitory phosphorylation of GSK-3β at Ser-9 in the brains of APPsw-tauvlw mice, and the levels of the inactive from of the enzyme in NP12 treated mice are comparable to those found in wild-type littermate controls (p=0.893) (n=6-8 for each treatment). NP12 treatment results in significantly decreased phosphorylation at the putative GSK-3β-directed sites Ser-202 (CP13) and Ser-396/404 (PHF-1) in 15-month-old mice by more than 60% (p=0.023 and p=0.024, respectively)[2]. Injection of Tideglusib (NP031112) (50 mg/kg) into the rat hippocampus dramatically reduces kainic acid-induced inflammation, as measured by edema formation using T2-weighted magnetic resonance imaging and glial activation and has a neuroprotective effect in the damaged areas of the hippocampus[3].

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