Tubastatin A

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Chemical Structure| 1252003-15-8 同义名 : -
CAS号 : 1252003-15-8
货号 : A161831
分子式 : C20H21N3O2
纯度 : 98%
分子量 : 335.4
MDL号 : MFCD18071463
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(35.78 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • HDAC6

    HDAC6, IC50:15 nM
描述 HDACs (Histone deacetylases) are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs, HDAC 1-11 and sirt 1-7[2]. Tubastatin A, a derivative from tubacin, is a selective HDAC6 inhibitor with IC50 value of 15nM (measured by purified human HDAC protein), over 1000-fold selectivity against HDAC1. Treatment of Tubastatin A with low concentration (2.5uM) results in an α-tubulin hyperacetylation, corresponding to HDAC6 inhibition, rather than histone hyperacetylation, corresponding to class I HDAC inhibition, which shows the selectivity to HDAC6 of tubastatin A. Tubastatin A possesses the function of modulation of several neurodegenerative diseases. In an HCA oxidative stress assay, tubastatin A displayed neuroprotection against HCA-induced neuronal cell death at 5-10 µM in a dose-dependent manner[1]. Tubastatin A can also increase autophagic flux and reduce diffuse mutant huntingtin in striatal neurons[3]. Compared with tubacin, tubastatin A possesses a drug-like property, which makes it more considered as a promising anti-cancer drug[4]. Combination with tubastatin A can enhance the TMZ-induced cytotoxicity in TMZ-resistant glioma cell lines at concentration < 30 μM[5].
作用机制 Tubastatin has a hydroxamate-based structure, which can chelate the Zn2+ ion of HDACs. [1]
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
human HeLa cells Function assay 6 h Inhibition of HDAC6 in human HeLa cells assessed as reduction in K40 hyperacetylation of alpha-tubulin incubated for 6 hrs by immunofluorescence assay, IC50=2.5 μM. 25454270
human Jurkat cells Cytotoxic assay 72 h Cytotoxicity against human Jurkat cells assessed as growth inhibition after 72 hrs by MTS assay, IC50=3.38 μM. 24304348
human KB cells Cytotoxic assay 72 h Cytotoxicity against human KB cells after 72 hrs by MTS assay, IC50=14.81 μM. 25899338
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.98mL

0.60mL

0.30mL

14.91mL

2.98mL

1.49mL

29.82mL

5.96mL

2.98mL
参考文献

[1]Butler KV, Kalin J, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc. 2010 Aug 11;132(31):10842-6.

[2]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[3]Guedes-Dias P, de Proen?a J, et al. HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces diffuse mutant huntingtin in striatal neurons. Biochim Biophys Acta. 2015 Nov;1852(11):2484-93.

[4]Lernoux M, Schnekenburger M, et al. Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways. Pharmacol Res. 2018 Mar;129:337-356.

[5]Li ZY, Zhang C, et al. A novel HDAC6 inhibitor Tubastatin A: Controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses Temozolomide-induced ER stress-tolerance in GBM cells. Cancer Lett. 2017 Apr 10;391:89-99.

[6]Wang Z, Leng Y, et al. Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation. Sci Rep. 2016.

[7]Gradilone SA, Radtke BN, et al. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 2013;73(7):2259-70.