Tubacin

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Chemical Structure| 537049-40-4 同义名 : -
CAS号 : 537049-40-4
货号 : A167094
分子式 : C41H43N3O7S
纯度 : 99%+
分子量 : 721.861
MDL号 : MFCD28144524
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: 105 mg/mL(145.46 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
动物实验配方：

2% DMSO+30% PEG 300+5% Tween 80+water 10 mg/mL

生物活性
靶点

  • HDAC6

    HDAC6, IC50:4 nM
描述 There are 18 mammalian HDACs, HDAC 1-11 and sirt 1-7. One of the member, HDAC6 can target specific substrates like HSP90 and α-tubulin which involve in protein trafficking and degradation or cell shape and migration, thus participates in the pathways relating to neurodegenerative diseases, cancer and immunology[3]. Tubacin has a high affinity to HDAC6 (Ki=142nM)[1] and inhibits HDAC6 potently and selectively with an IC50 value of 4nM (measured by purified human HDAC protein), approximately 350-fold selectivity over HDAC1[2]. Treatment with 2uM tubacin can strongly and selectively increase acetylation level of α-tubulin, corresponding to HDAC6 inhibition, in A549 cells after 19h, with no effect on histone acetylation[4]. Unlike Taxol, which increases α-tubulin acetylation by direct stabilization of microtubules, tubacin do not directly stabilize microtubules and has no overall effect on the morphology of A549 cells, yet with no effect on gene expression or cell-cycle progression, but it inhibits the migration of cells under normal culture conditions with concentration of 2uM, which may due to the inhibition of HDAC6’s functional role as a MAP or capacity to mediate the focal adhesion dynamics required for rapid cell migration[5][6]. Co-treatment with 17-AAG and tubacin can significantly augment the loss of survival of K562 cells and viability of AML and CML samples, which suggests that HDAC6 is an hsp90 client protein and can augment the anti-leukemia effects of 17-AAG[7].
作用机制 Tubacin inhibitd the HDAC6 by chelating a Zn++ ion through its hydroxamate structure and appears to alter the formation of complexes of HDAC6.[5][8]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human A549 cells Function assay Inhibition of HDAC6 in human A549 cells assessed as induction of alpha-tubulin acetylation by fluorescence microscopy, EC50=2.9 μM 16408003
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=2.9 μM 25454270
human T24 cells Function assay Induction of histone H3 acetylation in human T24 cells, EC50=2.9 μM 19111466
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.93mL

1.39mL

0.69mL

13.85mL

2.77mL

1.39mL
参考文献

[1]Estiu G, Greenberg E, et al. Structural origin of selectivity in class II-selective histone deacetylase inhibitors. J Med Chem. 2008;51(10):2898-906.

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

[3]Wang XX, Wan RZ, Liu ZP. Recent advances in the discovery of potent and selective HDAC6 inhibitors. Eur J Med Chem. 2018.

[4]Haggarty SJ, Koeller KM, et al. Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays. Chem Biol. 2003;10(5):383-96.

[5]Haggarty SJ, Koeller KM, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A. 2003;100(8):4389-94.

[6]Tran AD, Marmo TP, et al. HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J Cell Sci. 2007;120(Pt 8):1469-79.

[7]Rao R, Fiskus W, et al. HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells. Blood. 2008;112(5):1886-93.

[8]Cabrero JR, Serrador JM, et al. Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of its deacetylase activity. Mol Biol Cell. 2006;17(8):3435-45.

[9]Ota S, Zhou ZQ, Hurlin PJ. Suppression of FGFR3- and MYC-dependent oncogenesis by tubacin: association with HDAC6-dependent and independent activities. Oncotarget. 2018;9(3):3172-3187.

[10]Chan CT, Qi J, et al. Syntheses and discovery of a novel class of cinnamic hydroxamates as histone deacetylase inhibitors by multimodality molecular imaging in living subjects. Cancer Res. 2014;74(24):7475-86.