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Purity: ≥98%
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.
| ln Vitro |
In ATDC5 cells, thiamet G (1 μM) dramatically enhances the accumulation of O-GlcNAcylated protein. The buildup of O-GlcNAc brought on by thiamet G also significantly increased these MMPs' activity. JNK, ERK, and p38 are all phosphorylated when exposed to 1 μM of thiamet G, but not Akt[2]. Cell viability is not greatly affected by thiamet G (0.1–10 μM). Microtubule dynamics are changed and tau phosphorylation is decreased by thiamet G [3].
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| ln Vivo |
At 500 mg/kg/d, thiamet G decreases neurodegeneration and raises tau and global O-GlcNAc. In this transgenic model, thiamet G treatment prevented tau-driven neurodegeneration and increased motor neurons by 1.4 times. Therefore, Thiamet G treatment was ineffective in mice devoid of the P301L transgene, suggesting that Thiamet G treatment is only effective in preventing neurodegeneration and weight loss when the P301L transgene is present. O-GlcNAc is elevated in the brain and spinal cord tissue of Thiamet G-treated mice [1]. O-GlcNAc levels in the brain, liver, and knee joints of C57BL/6 mice are dose-dependently increased by thiamet G (20 mg/kg, i.p.) [2].
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| Animal Protocol |
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| References |
[1]. Yuzwa SA, et al. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol. 2012 Feb 26;8(4):393-9.
[2]. Andrés-Bergós J, et al. The increase in O-linked N-acetylglucosamine protein modification stimulates chondrogenic differentiation both in vitro and in vivo. J Biol Chem. 2012 Sep 28;287(40):33615-28. [3]. Ding N, et al. Thiamet-G-mediated inhibition of O-GlcNAcase sensitizes human leukemia cells to microtubule-stabilizing agent NSC 125973. Biochem Biophys Res Commun. 2014 Oct 24;453(3):392-7 |
| Molecular Formula |
C9H16N2O4S
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| Molecular Weight |
248.3
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| CAS # |
1009816-48-1
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| Related CAS # |
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| SMILES |
S1/C(=N\C([H])([H])C([H])([H])[H])/N([H])C2([H])[C@]1([H])OC([H])(C([H])([H])O[H])[C@]([H])(C2([H])O[H])O[H]
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline: 30 mg/mL Solubility in Formulation 5: 50 mg/mL (201.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0274 mL | 20.1369 mL | 40.2739 mL | |
| 5 mM | 0.8055 mL | 4.0274 mL | 8.0548 mL | |
| 10 mM | 0.4027 mL | 2.0137 mL | 4.0274 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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