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Tubastatin A

现货
Catalog No.
A4101
HDAC6抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
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10mg
¥ 500.00
现货
50mg
¥ 700.00
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100mg
¥ 1,200.00
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200mg
¥ 2,200.00
现货

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Background

Tubastatin A is a potent and selective inhibitor of HDAC6 with IC50 value of 15 nM [1].
Histone deacetylases (HDACs) and histone acetyltransferases (HATs) mediates the balance between histone deacetylation and acetylation. HDACs also regulate the acetylation status of signaling molecules, chaperones, and transcription factors that are non-histone proteins [2]. HDAC6 interacts with the HSP90 which is a molecular chaperone. The deacetylation of HSP90 by HDAC6 is important for the stability and of many client proteins including Bcr-Abl, c-Raf, and AKT. So, HDAC inhibitors have anti-cancer function [2].
Tubastatin A is a selective inhibitor of HDAC6 compared with other HDACs. Tubastatin A maintained an average 200-fold selectivity compared with class I HDACs. Tubastatin A displayed selectivity against all isoforms excluding HDAC8
over 1000-fold. Tubastatin A protected against HCA induced neuronal cell death in a dose-dependent manner. Tubastatin A induced the hyperacetylationof -tubulin at 2.5 μM[1]. In LPS stimulated human THP-1 macrophages, Tubastatin A displayed significant inhibition of IL-6and TNF with an IC50 of 712 nM and 212 nM [3]. Tubastatin A showed the inhibition of nitric oxide (NO) secretion with an IC50 of 4.2μM in murine Raw 264.7 macrophages [3]. Tubastatin-A also significantly inhibit cell proliferation at 10μM in KMCH cells [4].
Tubastatin A showed inhibition of paw volume at 30 mg/kg in an animal model of inflammation[3]. Tubastatin-A treatment reduced tumor growth and induces ciliogenesis in rat orthotopic model of cholangiocarcinoma at 10 mg/kg [4].
References:
1.Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP: Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010, 132(31):10842-10846.
2.Kim HJ, Bae SC: Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 2011, 3(2):166-179.
3.Vishwakarma S, Iyer LR, Muley M, Singh PK, Shastry A, Saxena A, Kulathingal J, Vijaykanth G, Raghul J, Rajesh N et al: Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects. Int Immunopharmacol 2013, 16(1):72-78.
4.Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, LaRusso NF: HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013, 73(7):2259-2270.

文献引用

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt335.4
Cas No.1252003-15-8
FormulaC20H21N3O2
Solubility≥10.75 mg/mL in DMSO, <2.28 mg/mL in EtOH, <2.58 mg/mL in H2O
Chemical NameN-hydroxy-4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzamide
SDFDownload SDF
Canonical SMILESCN(C1)CCC2=C1C3=C(N2CC4=CC=C(C(NO)=O)C=C4)C=CC=C3
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]:

细胞系

人乳腺癌细胞(MCF-7)

制备方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

15、30 μM,48 h.

实验结果

在MCF-7细胞中,tubastatin A以剂量依赖性方式抑制细胞增殖,IC50值为15 μM,并增加细胞质微管的乙酰化。此外,tubastatin A降低由冷和200 nM nocodazole诱导的微管解聚速率,其由HDAC6的抑制介导。

动物实验[2]:

动物模型

Wistar大鼠,DBA1小鼠

给药剂量

大鼠:30 mg/kg/day i.p. 5天,小鼠:30 mg/kg,q.d. 从第21天到第36天。

制备方法

溶于10%二甲亚砜(DMSO)10%聚乙二醇(PEG)400和80%(40%羟丙基β环糊精)。

实验结果

在FCA注射的大鼠中,tubastatin在2小时将足部体积显著减少71.9%。在半治疗胶原诱导的DBA1关节炎小鼠中,tubastatin(30 mg/kg/day, i.p.) 将关节炎的临床评分显著降低73%,并且抑制爪组织中59% 的IL-6生成。Tubastatin治疗的小鼠体重没有显著变化。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Asthana J, Kapoor S, Mohan R, et al. Inhibition of HDAC6 deacetylase activity increases its binding with microtubules and suppresses microtubule dynamic instability in MCF-7 cells. J Biol Chem, 2013, 288(31): 22516-22526.

[2]. Vishwakarma S, Iyer LR, Muley M, et al. Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects. Int Immunopharmacol, 2013, 16(1): 72-78.

生物活性

描述 Tubastatin A是一种有效的和选择性的HDAC6抑制剂,IC50值为15 nM。
靶点 HDAC6          
IC50 15 nM          

质量控制

化学结构

Tubastatin A

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