Thiamet G
Modify Date: 2025-08-25 19:12:29
Thiamet G structure
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Common Name | Thiamet G | ||
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| CAS Number | 1009816-48-1 | Molecular Weight | 248.299 | |
| Density | 1.8±0.1 g/cm3 | Boiling Point | 483.2±55.0 °C at 760 mmHg | |
| Molecular Formula | C9H16N2O4S | Melting Point | N/A | |
| MSDS | Chinese USA | Flash Point | 246.0±31.5 °C | |
| Symbol |
GHS07 |
Signal Word | Warning | |
Use of Thiamet GThiamet-G is a potent and selective inhibitor of OGA, which acts to remove O-GlcNAc from modified proteins, with Ki of 20 nM for human OGA. |
| Name | 2-(ethylamino)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol |
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| Synonym | More Synonyms |
| Description | Thiamet-G is a potent and selective inhibitor of OGA, which acts to remove O-GlcNAc from modified proteins, with Ki of 20 nM for human OGA. |
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| Related Catalog | |
| Target |
Ki: 20 nM (Human OGA)[1] |
| In Vitro | Thiamet G (1 μM) induces a clear increase in the accumulation of O-GlcNAcylated proteins of ATDC5 cells. O-GlcNAc accumulation induced by Thiamet G also evokes a clear increase in the activity of these MMPs. Thiamet G (1 μM) induces the phosphorylation of JNK, ERK, and p38 but not phosphorylation of Akt[2]. Thiamet G (0.1-10 μM) does not significantly affect the cell viability. Thiamet G decreases phosphorylation of tau and alters the microtubule dynamics[3]. |
| 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]. |
| Kinase Assay | All enzymatic assays are performed in triplicate at 37°C using 4-methylumbelliferyl N-acetyl-β-d-glucosaminide dehydrate as substrate. 1 nM of purified OGA is incubated with the compounds for 5 min, and then 0.2 mM of the substrate is added. The liberation of 4-methylumbellifery is monitored by kinetic reading at excitation/emission 355/460 nm using a Tecan M200 plate in a mode of 60 s/cycle and 15 cycles in total. |
| Cell Assay | Jurkat cells are seeded at 6000 cells/well in a 96-well plate, and 12 h later, cells are treated with compounds for the indicated time. Cell viability is determined by XTT assay. |
| Animal Admin | For the Thiamet G dose dependence study, six 23-day-old male C57BL/6 mice receive single intraperitoneal injections of either 0, 10, 20, 100, 200, or 500 mg/kg of Thiamet G dissolved in phosphate-buffered saline (PBS) and then are euthanized 8 h later to evaluate the O-GlcNAc levels in different tissues (brain, liver, muscle, and knee). The time of sacrifice is chosen on the basis of previously published data on Thiamet G in rodents, which demonstrates that the peak level of O-GlcNAc proteins following administration of the drug is achieved after 8-10 h. Tissues are collected immediately after sacrifice, flash-frozen in liquid nitrogen, and stored at −80°C until required for use. |
| References |
| Density | 1.8±0.1 g/cm3 |
|---|---|
| Boiling Point | 483.2±55.0 °C at 760 mmHg |
| Molecular Formula | C9H16N2O4S |
| Molecular Weight | 248.299 |
| Flash Point | 246.0±31.5 °C |
| Exact Mass | 248.083084 |
| PSA | 119.61000 |
| LogP | -0.09 |
| Vapour Pressure | 0.0±2.8 mmHg at 25°C |
| Index of Refraction | 1.729 |
| Storage condition | -20℃ |
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Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.
Molecular Neurodegeneration 9 , 42, (2014) Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-tran... |
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Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation.
Nat. Chem. Biol. 8(4) , 393-9, (2012) 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 ... |
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A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.
.PubMed ID Pathological hyperphosphorylation of the microtubule-associated protein tau is characteristic of Alzheimer's disease (AD) and the associated tauopathies. The reciprocal relationship between phosphoryl... |
| Thiamet G |
| Thiamet G0nDiscontinued |
| (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 |
| 5H-Pyrano[3,2-d]thiazole-6,7-diol, 2-(ethylamino)-3a,6,7,7a-tetrahydro-5-(hydroxymethyl)-, (3aR,5R,6S,7R,7aR)- |