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ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors Thiamet GDiscontinued

Thiamet GDiscontinued Structure

Thiamet GDiscontinued

Product NameThiamet GDiscontinued
CAS1009816-48-1
MFC9H16N2O4S
MW248.3
EINECS
MOL File1009816-48-1.mol

Chemical Properties

Boiling point	483.2±55.0 °C(Predicted)
Density	1.74±0.1 g/cm3(Predicted)
storage temp.	-20°C
solubility	H2O: ≥5mg/mL at warmed to 60°C
form	powder
pka	13.17±0.70(Predicted)
color	white to beige
optical activity	[α]/D -21 to -26°, c = 0.3 in methanol
Water Solubility	H2O: ≥5mg/mL atwarmed to 60°C
Stability	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
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
InChIKey	PPAIMZHKIXDJRN-UKPHHSARSA-N
SMILES	S1[C@@]2([H])O[C@H](CO)[C@@H](O)[C@H](O)[C@@]2([H])N=C1NCC

Safety Information

WGK Germany	3
Storage Class	11 - Combustible Solids
Hazard Classifications	Skin Sens. 1B

Usage And Synthesis

Description

Thiamet G (1009816-48-1) is a potent, selective inhibitor of O-GlcNAcase (Ki= 21 nM for human O-GlcNAcase). Increases levels of O-GlcNAc-modified proteins in cellular assays andin vivo. Suppresses phosphorylation of tau protein in rat cortex and hippocampus.1Stabilizes tau against aggregation and slows neurodegeneration.2Thiamet G prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.3Elevates soluble tau species and reduces tauopathy in mouse models.4Activein vivoand blood brain barrier permeable.

Uses

A potent O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. The authors anticipate that Thiamet-G will find wide use in probing the functional role of O-GlcNAc in vertebrate brain, and it may also offer a route to blocking pathological hyperphosphorylation of tau in AD. Anti-Alzheimer''s agent.

Uses

As a potent O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo, The authors anticipate that Thiamet-G will find wide use in probing the functional role of O-GlcNAc in vertebrate brain, and it may also offer a route to blocking pathological

Biochem/physiol Actions

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.

in vivo

Thiamet G (500 mg/kg/d) increases global and tau O-GlcNAc and reduces neurodegeneration. Thiamet G-treated group has 1.4-fold more motor neurons and hinders tau-driven neurodegeneration within this transgenic model. Thiamet G treatment therefore has no detectable effect on mice lacking the P301L transgene, indicating that prevention of neurodegeneration and weight loss is mediated by Thiamet G treatment only in the context of the P301L transgene. In Thiamet G-treated mice, the O-GlcNAc increases in the brain and spinal cord tissues^[1].
Thiamet G (20 mg/kg, i.p.) increases O-GlcNAc levels in brain, liver, and knee of the C57BL/6 mice in a dose-dependent manner^[2].

storage

Store at -20°C

References

[1] SCOTT A YUZWA. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo[J]. Nature chemical biology, 2008, 4 8: 483-490. DOI:10.1038/nchembio.96
[2] SCOTT A YUZWA. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation[J]. Nature chemical biology, 2012, 8 4: 393-399. DOI:10.1038/nchembio.797
[3] SCOTT A YUZWA. Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.[J]. Molecular Neurodegeneration, 2014, 9: 42. DOI:10.1186/1750-1326-9-42
[4] NICHOLAS B HASTINGS. Inhibition of O-GlcNAcase leads to elevation of O-GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice.[J]. ACS Combinatorial Science, 2017: 39. DOI:10.1186/s13024-017-0181-0

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