Thiamet G is a potent, selective, and blood brain barrier permeable inhibitor of O-GlcNAcase that demonstrates a Ki value of 21 nM. This compound has been shown to increase cellular O-GlcNAc-modified protein levels (EC50 = 30 nM) and block phosphorylation of tau protein both in cultured PC-12 cells and in rats. Research has shown that hyperphosphorylation of the tau protein can lead to its aggregation and subsequent formation of neurofibrillary tangles, a hallmark of Alzheimer's disease and other tauopathic, neurodegenerative disorders. Tau is also dynamically modified by the addition and cleavage of O-linked β-N-acetylglucosamine (O-GlcNAc) moieties, which is mediated in part by O-GlcNAcase. Levels of O-GlcNAcylated proteins from Alzheimer's disease brain extracts are decreased as compared to that in controls, suggesting that impaired brain glucose metabolism may contribute to pathogenesis.
1. Liu, F., et al. 2004. Proc. Natl. Acad. Sci. U.S.A. 101: 10804-10809. PMID: 15249677 2. Yuzwa, S.A., et al. 2008. Nat. Chem. Biol. 4: 483-490. PMID: 18587388
Soluble in water (3 mg/ml at 25.0° C), ethanol (~0.5 mg/ml), DMSO (~20 mg/ml), DMF (~20 mg/ml), and PBS(pH7.2) (~3 mg/ml).
Store at -20° C
483.21° C at 760 mmHg (Predicted)
1.75 g/cm3 (Predicted)
n20D 1.73 (Predicted)
PC-12: EC5050 = 30 nM (rat)
NCOAT: Ki= 21 nM (human)
pKa: 13.17 (Predicted), pKb: 6.43 (Predicted)
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.
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