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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.

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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
MDL No. :MFCD28144524
InChI Key :BHUZLJOUHMBZQY-YXQOSMAKSA-N
Pubchem ID :6675804

Safety of Tubacin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Tubacin

epigenetics

Isoform Comparison

Biological Activity

Target
  • HDAC6

    HDAC6, IC50:4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MDCK.2 cells 10 μM days 0, 2, 4, 6, 8, 10, 12, 14 Treatment with tubacin prevented cyst formation in MDCK cells, an in vitro model of cystogenesis, and slowed cyst growth. PMC4912414
PH2 cells 10 μM 17 hours Tubacin significantly inhibited the proliferation of PH2 cells and increased tubulin acetylation. PMC4912414
PN18 cells 10 μM 17 hours Tubacin significantly inhibited the proliferation of PN18 cells and increased tubulin acetylation. PMC4912414
HCT116 cells 5 µM 6 hours Tubacin treatment resulted in rapid FLIP protein downregulation and caused an increase in acetylation of α-tubulin. PMC3392639
A549 cells 0.3 - 10 µM 16 hours Tubacin in combination with paclitaxel synergistically increased tubulin acetylation, indicating that functional inhibition of HDAC6 is associated with increased tubulin acetylation. PMC1861827
A549 cells 10 µM 20 hours To examine the effect of Tubacin on acetylated α-tubulin and acetylated lysine levels in A549 cells, results showed that Tubacin significantly increased the level of acetylated α-tubulin. PMC153564
NIH 3T3 cells 2 µM 4 hours To examine the effect of Tubacin on acetylated α-tubulin levels in NIH 3T3 cells, results showed that Tubacin significantly increased the level of acetylated α-tubulin, and this increase was suppressed in HDAC6-overexpressing cells. PMC153564
HEK293 cells 2 µM 16 hours To assess HDAC6 activity, it was found that the half-life of acetylated α-tubulin was prolonged in ATP13A2-null cells. PMC6314552
Mecp2 null mouse embryonic fibroblasts (MEFs) 1 µM 48 hours Tubacin significantly restored the percentage of ciliated Mecp2 null MEFs, indicating that microtubule stabilization can rescue the observed ciliary phenotypes. PMC7278541
Mecp2 null cortical neurons 1 µM 48 hours Tubacin treatment significantly restored the percentage of ciliated cells in Mecp2 null neurons, indicating that microtubule stabilization can rescue ciliary phenotypes in neurons. PMC7278541
RTT patient fibroblasts 250 nM 24 hours Tubacin treatment caused a significant cilium elongation in most of the mutant cells, thus rescuing the structural defect of primary cilium. PMC7278541
mouse oocytes 2 µM 12 hours Inhibiting HDAC6 activity to restore microtubule acetylation levels and spindle morphology in TUBB8-D417N mutant oocytes PMC11746963

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
mice Pkd1fl/fl;Pax8rtTA;TetO-cre mouse model intraperitoneal injection 150 mg/kg Once daily for 12 days Tubacin significantly slowed renal cyst growth in Pkd1fl/fl;Pax8rtTA;TetO-cre mice and improved renal function. PMC4912414
Chick embryo Chick embryo Filter paper soaked 0.25 mg/kg every 4 days for one month To investigate the effect of Tubacin on angiogenesis in chick embryos, results showed that Tubacin significantly inhibited blood vessel growth. PMC4875255
mice TUBB8-D417N mutant mouse model cultured in medium 3 mg/kg Every 4 days until the end of the experiment Inhibiting HDAC6 activity to restore microtubule acetylation levels and spindle morphology in TUBB8-D417N mutant oocytes PMC11746963

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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