| Identification | Back Directory | [Name]
Thiamet G Discontinued | [CAS]
1009816-48-1 | [Synonyms]
CS-1700
Thiamet G
Thiamet G Discontinued
Thiamet G0nDiscontinued
Thiamet G_x000b_Discontinued
1,2-Dideoxy-2'-ethylamino-a-D-glucopyranoso-[2,1-d]-2'-thiazoline
2-(ethylaMino)-5-(hydroxyMethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-dio
(3aR,5R,6S,7R,7aR)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5-(hydroxymethyl)-5H-Pyrano[3,2-d]thiazole-6,7-diol
(3aR,5R,6S,7R,7aR)-2-(Ethylamino)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol
5H-Pyrano[3,2-d]thiazole-6,7-diol, 2-(ethylamino)-3a,6,7,7a-tetrahydro-5-(hydroxymethyl)-, (3aR,5R,6S,7R,7aR)-
(3aR,5R,6S,7R,7aR)-2-(ethylamino)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol | [Molecular Formula]
C9H16N2O4S | [MDL Number]
MFCD15144964 | [MOL File]
1009816-48-1.mol | [Molecular Weight]
248.299 |
| Chemical Properties | Back Directory | [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 Rotation]
[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 |
| Hazard Information | Back Directory | [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 and?in vivo. Suppresses phosphorylation of tau protein in rat cortex and hippocampus.1?Stabilizes tau against aggregation and slows neurodegeneration.2?Thiamet G prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.3?Elevates soluble tau species and reduces tauopathy in mouse models.4?Active?in vivo?and blood brain barrier permeable. | [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) Yuzwa?et al. (2008),?A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo; Nat. Chem. Biol.,?4?483
2) Yuzwa?et al. (2012),?Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation; Nat. Chem. Biol.?8?393
3) Yuzwa?et al. (2014),?Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice; Mol. Neurodegener.,?9?42
4) Hastings?et al.?(2017)?Inhibition of O-GlcNAcase leads to elevation of O-GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice;?Mol. Neurodegener.,?12?39 |
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