Thiamet-G

Thiamet-G is a potent inhibitor of the enzyme O-GlcNAcase (Ki = 21 nM). The compound is orally bioavailable and crosses the blood brain barrier. Thiamet-G leads to an increase in O-GlcNAc-modified proteins in cell-based and in vivo assay systems, and reduces levels of phosphorylated Tau protein in rat cortex and hippocampus.

Product information

CAS Number: 1009816-48-1

Molecular Weight: 248.30

Formula: C9H16N2O4S

Synonym:

Thiamet G

Chemical Name: (3aR, 5R, 6S, 7R, 7aR, E)-2-(ethylimino)-5-(hydroxymethyl)hexahydro-1H-pyrano[3, 2-d]thiazole-6, 7-diol

Smiles: CC/N=C1\N[C@H]2[C@H](O[C@H](CO)[C@@H](O)[C@@H]2O)S\1

InChiKey: PPAIMZHKIXDJRN-FMDGEEDCSA-N

InChi: InChI=1S/C9H16N2O4S/c1-2-10-9-11-5-7(14)6(13)4(3-12)15-8(5)16-9/h4-8,12-14H,2-3H2,1H3,(H,10,11)/t4-,5-,6-,7-,8-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 12.4 mg/mL (50 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

In NGF-differentiated PC-12 cells, inhibition of O-GlcNAcase by Thiamet G increases the cellular levels of O-GlcNAc with EC50 of approximately 30 nM. Thiamet G (100 mM) reduces tau phosphorylation by approximately 2.1-fold, 2.7-fold, 1.2-fold and 1.3-fold for Ser396, Thr231, Ser422 and Ser262, respectively. Thiamet G (12.5 nM and 25 nM) significantly enhances p38 phosphorylation by increasing O-GlcNAcylation in mesangial cells. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, thiamet-G restores the assembly of the spindle and partially rescues histone phosphorylation.

In Vivo:

In rats, thiamet G (50 mg/kg) administrated by i.v. crosses the blood brain barrier and then results in increase in brain O-GlcNAc levels in a dose- and time-dependent manner, and reduction of tau phosphorylation in rat brain. Thiamet G is also orally bioavailable. O-GlcNAc accumulation induced by thiamet G stimulates chondrogenic differentiation in C57/bl mice by increasing the gene expression of differentiation markers, as well as the activity of MMP-2 and -9.

References:

1. Liu, F., Iqbal, K., Grundke-Iqbal, I., et al. O-GlnNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America 101(29), 10804-10809 (2004).
2. Yuzwa, S.A., Macauley, M.S., Heinonen, J.E., et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nature Chemical Biology 4(8), 483-490 (2008).

Products are for research use only. Not for human use.