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Tubacin

现货
Catalog No.
A4501
HDAC6有效的、选择性、可逆的、细胞通透性的抑制剂。
组合的产品项目
规格价格库存 数量
1mg
¥ 750.00
现货
5mg
¥ 2,500.00
现货
10mg
¥ 4,700.00
Ship with 10-15 days

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Background

Tubacin is a potent, selective, reversible, and cell-permeable inhibitor of HDAC6 with an IC50 value of 4 nM.[1]
Histone deacetylases (HDACs) can be divided into 4 classes, among whom Class I, II, and IV is nuclear zinc-dependent enzymes and Class III is nicotinamide adenine dinucleotide (NAD+) dependent. HDACs catalyze deacetylation of N-acetyl-lysine residues and play an important role in a number of biological reactions including gene expression and cell cycle. By inhibiting α-tubulindeacetylation in mammalian cells, tubacin can suppress the expression of certain genes and therefore result in an antitumor effect without the level of histone acetylation. As selective inhibitors of HDAC6 are used in the treatment of protein degradation disorders, tubacin may have therapeutic applications as antimetastatic and antiangiogenic agent.[1,2]
Tubacin exhibited potent inhibition on HDAC6, with an IC50 value of 4 nM and approximately 350-fold selectivity over HDAC1. In cultured A549 cells, 10 μM tubacin induced up to a 3-fold increase in the relative α-tubulin- acetylation level, with an EC 50 of 2.5 μM. Acute lymphoblastic leukemia (ALL) and normal cells were treated with different concentrations of tubacin ranging from 0.5 to 2.5 mM or controls. The results indicated that tubacin inhibited the growth of ALL cells dose-dependently, with IC50 ranging from 1.2 to 2 mM. Moreover, ALL cells have a greater sensitivity to tubacin compared to other normal cells.[1,2,3]
Tuacin also showed suppressing activity in the growth of ALL cells in vivo. By treating pre-B ALL cells injected mice, the mice in experimental group survival were prolonged comparing with the control. Besides, tubacin treated HEK cells transfected with tau significantly attenuate tau phosphorylation at T231, which also revealed it may play an important role in the pathology of Alzheimer's Disease(AD). [3,4]
Reference:
1.Butler K V, Kalin J, Brochier C, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A[J]. Journal of the American Chemical Society, 2010, 132(31): 10842-10846.
2.Haggarty S J, Koeller K M, Wong J C, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation[J]. Proceedings of the National Academy of Sciences, 2003, 100(8): 4389-4394.
3.Aldana-Masangkay G I, Rodriguez-Gonzalez A, Lin T, et al. Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells[J]. Leukemia & lymphoma, 2011, 52(8): 1544-1555.
4.Xu K, Dai X L, Huang H C, et al. Targeting HDACs: a promising therapy for Alzheimer's disease[J]. Oxidative medicine and cellular longevity, 2011, 2011.

文献引用

1.Hari Prasad, Rajini Rao. "The Amyloid Clearance Defect in ApoE4 Astrocytes is Corrected by Epigenetic Restoration of NHE6." bioRxiv. 2018.January. 4
2.Sedgwick A, Olivia Balmert M, et al. "The formation of giant plasma membrane vesicles enable new insights into the regulation of cholesterol efflux." Exp Cell Res. 2018 Apr 15;365(2):194-207. PMID:29522754
3.Yan Y, Wang H, et al. "HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila." Dev Cell. 2017 Oct 9;43(1):99-111.e5. PMID:28966044

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt721.86
Cas No.537049-40-4
FormulaC41H43N3O7S
Solubility≥7.19mg/mL in DMSO, <2.29 mg/mL in EtOH, <2.3 mg/mL in H2O
Chemical NameN-[4-[(2R,4R,6S)-4-[(4,5-diphenyl-1,3-oxazol-2-yl)sulfanylmethyl]-6-[4-(hydroxymethyl)phenyl]-1,3-dioxan-2-yl]phenyl]-N'-hydroxyoctanediamide
SDFDownload SDF
Canonical SMILESC1C(OC(OC1C2=CC=C(C=C2)CO)C3=CC=C(C=C3)NC(=O)CCCCCCC(=O)NO)CSC4=NC(=C(O4)C5=CC=CC=C5)C6=CC=CC=C6
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

人A549肺癌细胞,小鼠NIH 3T3野生型(Neo),HDAC6,HDAC6双突变体和HDAC6过表达细胞,急性淋巴细胞白血病(ALL)细胞

溶解方法

该化合物在DMSO中的溶解度有限。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

2 μM,4.5 h

应用

在培养的细胞中,tubacin(10 μM)将α-微管蛋白乙酰化水平增加3倍,EC50为2.5μM。Tubacin(2 μM)抑制野生型和HDAC6过表达细胞的迁移。Tubacin增加了HDAC6与间期细胞中乙酰化微管的共定位。Tubacin在前B细胞和T细胞ALL细胞中诱导凋亡。

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]. Haggarty S J, Koeller K M, Wong J C, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation[J]. Proceedings of the National Academy of Sciences, 2003, 100(8): 4389-4394.

[2]. Aldana-Masangkay G I, Rodriguez-Gonzalez A, Lin T, et al. Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells[J]. Leukemia & lymphoma, 2011, 52(8): 1544-1555.

生物活性

描述 Tubacin是HDAC6有效的、选择性、可逆的、细胞通透性的抑制剂,IC50值4 nM。
靶点 HDAC6          
IC50 4 nM          

质量控制

化学结构

Tubacin

相关生物数据

Tubacin

相关生物数据

Tubacin

相关生物数据

Tubacin