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Description: Thiamet G is a novel potent, and selective O-GlcNAcase (OGA) inhibitor with Ki of 21 nM, it displayed 37, 000-fold selectivity over human lysosomal–hexosaminidase. Oligomerization of tau is a key process contributing to the progressive death of neurons in Alzheimer's disease. Tau is modified by O-linked N-acetylglucosamine (O-GlcNAc), and O-GlcNAc can influence tau phosphorylation in certain cases. O-GlcNAc also inhibits thermally induced aggregation of an unrelated protein, TAK-1 binding protein, suggesting that a basic biochemical function of O-GlcNAc may be to prevent protein aggregation. These results also suggest O-GlcNAcase as a potential therapeutic target that could hinder progression of Alzheimer's disease. Thiamet G was extremely stable in aqueous solution. In nerve growth factor (NGF)-differentiated PC-12 cells, thiamet G significantly increased cellular O-GlcNAc levels with EC50 value of 30 nM in a dose dependent way.
References: Nat Chem Biol. 2008 Aug; 4(8):483-90; Am J Physiol Endocrinol Metab. 2011 Oct; 301(4):E713-26.
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