product name Tubacin
Description: Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM in a cell-free assay, is has 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 showed that tubacin inhibited the growth of ALL cells dose-dependently, with IC50 ranging from 1.2 to 2 mM.
References: J Am Chem Soc. 2010 Aug 11;132(31):10842-6; Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4389-94; Protein Cell. 2011 Feb;2(2):150-60.
721.86
Formula
C41H43N3O7S
CAS No.
537049-40-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (138.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 10 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425452
| In Vitro |
In vitro activity: Tubacin, without directly stabilizing microtubules, induces an increase in α-tubulin acetylation with EC50 of 2.5 μM in A549 cells. Tubacin inhibits HDAC6-mediated α-tubulin deacetylation, and inhibits the migration of both wild-type and HDAC6-overexpressing cells. Tubacin, in combination with paclitaxel, synergistically enhances tubulin acetylation. Tubacin significantly inhibits both drug-sensitive and drug–resistant MM cell growth with IC50 of 5–20 μM, and induces cell apoptosis by activation of caspases. Kinase Assay: Enzyme inhibition assays are performed using the Reaction Biology HDAC Spectrum platform. The HDAC1, 2, 4, 5, 6, 7, 8, 9, 10, and 11 assays used isolated recombinant human protein; HDAC3/NcoR2 complex is used for the HDAC3 assay. Substrate for HDAC1, 2, 3, 6, 10, and 11 assays is a fluorogenic peptide from p53 residues 379-382 (RHKKAc); substrate for HDAC8 is fluorogenic diacyl peptide based on residues 379-382 of p53 (RHKAcKAc). Acetyl-Lys(trifluoroacetyl)-AMC substrate is used for HDAC4, 5, 7, and 9 assays. Compounds are dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 30 μM. Control Compound Trichostatin A (TSA) is tested in a 10-dose IC50 with 3-fold serial dilution starting at 5 μM. IC50 values are extracted by curve-fitting the dose/response slopes. Cell Assay: The inhibitory effect of bortezomib and/or tubacin on MM cell growth is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye absorbance. Cell lines used: Drug-sensitive (MM.1S, U266, INA-6, and RPMI8226) and drug-resistant (RPMI-LR5 and RPMI-Dox40) MM cell lines |
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| In Vivo | In chick embryos, inhibition of HDAC6 activity by Tubacin reduces the formation of new blood vessels in matrigel/nylon mesh. In angioreactors implanted in mice, Tubacin also impairs the formation of new blood vessels. |
| Animal model | |
| Formulation & Dosage | |
| References | J Am Chem Soc. 2010 Aug 11;132(31):10842-6; Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4389-94; Protein Cell. 2011 Feb;2(2):150-60. |
