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Chemical Structure| 537049-40-4 Chemical Structure| 537049-40-4

Structure of Tubacin
CAS No.: 537049-40-4

Chemical Structure| 537049-40-4

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Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM in a cell-free assay, approximately 350-fold selectivity over HDAC1.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Joshi, Ameya ; Ratnapradipa, Natasha ; Hughes, Jayce ; Moore, Erik ; Ekpenyong, Andrew ; Shukla, Surabhi

Abstract: Introduction: Glioblastoma (GBM) is a grade 4 brain tumor that originates in astrocytes. GBM has a high death rate and a very low median patient survival rate of 14–16 months, even with well-established treatment regimens. The majority of preclinical models assess the effectiveness of molecular leads on two-dimensional (2D) cell cultures, which may provide insight into toxicity against particular genotypes of GBM but do not provide insight into the mechanism of action of the therapeutic drug. Three-dimensional (3D) cultures present an attractive alternative due to their ability to closely model in vivo tumor-like conditions. Methods: In the present study, we used a rotary technique to culture 3D cancer spheroids of the T98G cell line. Initially, we estimated the relative potency of (HDAC) inhibitors, which are molecular leads currently in clinical trials as epigenetic therapy for GBM, on 2D and 3D cultures of T98G. We characterized the effect of the 3D half-maximal inhibitory concentrations (IC50) on spheroids using a live–dead assay to figure out which inhibitors inhibited cell viability in 3D the most. Finally, we checked the effects of the non-specific and specific inhibitors on tumor migration dynamics using an electric cell impedance sensing (ECIS) device with the help of two parameters—rate of migration (ROM) and late resistance (LR). Results and discussion: Our results show that the specific HDAC-6 inhibitor had a more potent anti-proliferative effect in both the cytotoxicity and live–dead assays. The non-specific inhibitor surprisingly promoted migration in the cells at its 2D IC50 value treatment, and none of the inhibitors was able to significantly decrease late resistance compared to untreated controls, indicating the need for the development of more potent inhibitors for monotherapy for GBM.

Keywords: glioblastoma ; inhibitors ; ; Trichostatin-A ; ; temozolomide

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Product Details of Tubacin

CAS No. :537049-40-4
Formula : C41H43N3O7S
M.W : 721.86
SMILES Code : O=C(NC1=CC=C([C@@H]2O[C@H](C3=CC=C(CO)C=C3)C[C@H](CSC4=NC(C5=CC=CC=C5)=C(C6=CC=CC=C6)O4)O2)C=C1)CCCCCCC(NO)=O
English Name :rel-N1-(4-((2R,4R,6S)-4-(((4,5-Diphenyloxazol-2-yl)thio)methyl)-6-(4-(hydroxymethyl)phenyl)-1,3-dioxan-2-yl)phenyl)-N8-hydroxyoctanediamide
MDL No. :MFCD28144524
InChI Key :BHUZLJOUHMBZQY-YXQOSMAKSA-N
Pubchem ID :6675804

Safety of Tubacin

Related Pathways of Tubacin

epigenetics
DNA

Isoform Comparison

Biological Activity

Target
  • HDAC6

    HDAC6, IC50:4 nM

Protocol

Bio Calculators
Preparing Stock Solutions 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

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[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.

 

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