Thiamet G
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Thiamet G是一种有效的O-GlcNAcase选择性抑制剂,Ki值为21 nM[1].
O-GlcNAcase是一种将GlcNAc从蛋白质上移除的酶.O-GlcNAcylation是指N-乙酰-葡糖胺基团与蛋白质苏氨酸和丝氨酸残基发生O-连接的翻译后修饰[2].
Thiamet G是一种有效的O-GlcNAcase选择性抑制剂.在动力学试验中,thiamet G可完全抑制人类O-GlcNAcase,Ki值为21 nM.Thiamet G在水溶液中极其稳定.在神经生长因子(NGF)分化的PC-12细胞中,thiamet G可通过剂量依赖的方式显著提高胞内O-GlcNAc水平,EC50值为30 nM.Thiamet G可显著降低Tau蛋白上Ser396和Thr231的磷酸化水平,分别减少2.1倍和2.7倍.并且,thiamet G可降低Ser422和Ser262的磷酸化水平[1].Thiamet G可显著地使人类白血病细胞系对微管稳定剂紫杉醇敏感[2].
在大鼠中,thiamet G可随意通过血脑屏障,并能剂量依赖地提高大脑O-GlcNAc水平.Thiamet G可分别降低tau在Ser396\Thr231和Ser422上的磷酸化2.7\3.1和1.8倍[1].
参考文献：
[1]. Yuzwa SA, Macauley MS, Heinonen JE, et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol, 2008, 4(8): 483-490.
[2]. Ding N, Ping L, Shi Y, et al. Thiamet-G-mediated inhibition of O-GlcNAcase sensitizes human leukemia cells to microtubule-stabilizing agent paclitaxel. Biochem Biophys Res Commun, 2014, 453(3): 392-397.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 248.3 |
| Cas No. | 1009816-48-1 |
| Formula | C9H16N2O4S |
| Solubility | ≥100 mg/mL in H2O; ≥12.4 mg/mL in DMSO; ≥2.64 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-(ethylamino)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol |
| SDF | Download SDF |
| Canonical SMILES | CCNC1=NC2C(C(C(OC2S1)CO)O)O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验 [1,2]: | |
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细胞系 |
PC-12细胞，系膜细胞 |
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溶解方法 |
该化合物在DMSO中的溶解度大于12.4 mg/mL。若获取更高浓度的溶液，可在37℃下孵育10分钟，随后在超声波浴中摇匀。-20℃以下可储存数月。 |
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反应条件 |
1 nM-250 mM，24 h |
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应用 |
在PC-12细胞中，Thiamet-G在包括Thr231和Ser396在内的病理相关位点处减少tau磷酸化。在PC-12细胞中，Thiamet-G处理24小时，浓度为1 nM至250 mM的Thiamet-G以剂量依赖性方式增加细胞O-GlcNAc水平。Thiamet G（12.5 nM和25 nM）通过增加肾小球系膜细胞中的O型GlcNAc糖基化显著增强p38磷酸化。 |
| 动物实验 [1,3]: | |
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动物模型 |
雄性Sprague-Dawley大鼠，C57/bl小鼠 |
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给药剂量 |
静脉注射，50 mg/kg |
|
应用 |
在大鼠中，静脉注射thiamet G（50 mg/kg）穿过血脑屏障，然后以剂量和时间依赖性方式增加脑O-GlcNAc水平，并且降低海马CA1区域中tau蛋白磷酸化。在C57/b1小鼠中，thiamet G诱导的O型GlcNAc糖基化积累通过增加分化标志物的基因表达以及MMP-2和-9的活性，刺激软骨细胞分化。 |
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注意事项 |
由于实验环境的不同，实际溶解度可能与理论值略有不同，请测试室内所有化合物的溶解度。 |
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References: [1]. 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[J]. Nature chemical biology, 2008, 4(8): 483-490. [2]. Goldberg H, Whiteside C, Fantus I G. O-linked β-N-acetylglucosamine supports p38 MAPK activation by high glucose in glomerular mesangial cells[J]. American Journal of Physiology-Endocrinology and Metabolism, 2011, 301(4): E713-E726. [3].Andrés-Bergós J, Tardio L, Larranaga-Vera A, et al. The increase in O-linked N-acetylglucosamine protein modification stimulates chondrogenic differentiation both in vitro and in vivo[J]. Journal of Biological Chemistry, 2012, 287(40): 33615-33628. |
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质量控制和MSDS
- 批次:
化学结构
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