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Thiamet G

现货
Catalog No.
B2048
O-GlcNAcase抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
现货
5mg
¥ 680.00
现货
25mg
¥ 2,590.00
现货

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Background

Thiamet G is a potent and selective inhibitor of O-GlcNAcase with Ki value of 21 nM [1].

O-GlcNAcase is an enzyme that removes GlcNAc from proteins. O-GlcNAcylation refers to the posttranslational modification of O-linkage of N-acetyl-glucosamine moieties to threonine and serine residues on proteins [2].

Thiamet G is a potent and selective O-GlcNAcase inhibitor. In kinetic assays, thiamet G competitively inhibited human O-GlcNAcase with Ki value of 21 nM. 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. Thiamet G significantly reduced phosphorylation levels at Ser396 and Thr231 of Tau by 2.1-fold and 2.7-fold, respectively. Also, thiamet G decreased the phosphorylation levels at Ser422 and Ser262 [1]. Thiamet G significantly sensitized human leukemia cell lines to paclitaxel, a microtubule-stabilizing agent [2].

In rats, thiamet G could readily cross the blood brain barrier and dose-dependently increased brain O-GlcNAc levels. Thiamet G reduced tau phosphorylation at Ser396, Thr231 and Ser422 by 2.7, 3.1 and 1.8-fold, respectively [1].

References:
[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.

文献引用

1. Li T, Li X, et al. "O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity." Cell Host Microbe. 2018 Dec 12;24(6):791-803.e6. PMID:30543776

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt248.3
Cas No.1009816-48-1
FormulaC9H16N2O4S
Solubility≥12.4mg/mL in DMSO, ≥100mg/mL in H2O
Chemical Name2-(ethylamino)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol
SDFDownload SDF
Canonical SMILESCCNC1=NC2C(C(C(OC2S1)CO)O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验 [1,2]:

细胞系

PC-12细胞,系膜细胞

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。

反应条件

1 nM-250 mM,24 h

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]:

动物模型

雄性Sprague-Dawley大鼠,C57/bl小鼠

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。

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。

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.

质量控制

化学结构

Thiamet G

相关生物数据

Thiamet G