Trichostatin A (TSA)

Catalog No.S1045

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.

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Trichostatin A (TSA) Chemical Structure

Trichostatin A (TSA) Chemical Structure
Molecular Weight: 302.4

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Related Compound Libraries

Trichostatin A (TSA) is available in the following compound libraries:

HDAC Inhibitors with Unique Features

Product Information

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  • Research Area
  • Trichostatin A (TSA) Mechanism
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.
Targets HDAC [1]
(Cell-free assay)
IC50 ~1.8 nM
In vitro Trichostatin A inhibits the proliferation of eight breast carcinoma cell lines including MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3 with mean IC50 of 124.4 nM (range, 26.4-308.1 nM), with more potency against cell lines that express ERα than the ERα-negative cell lines. Trichostatin A inhibits HDAC activity similarly in all the breast cancer cell lines with mean IC50 of 2.4 nM (range, 0.6-2.6 nM), and results in pronounced histone H4 hyperacetylation. [1] Unlike Trapoxin (TPX) and Chlamydocin which potently inhibit HDAC1 or HDAC4 but not HDAC6, Trichostatin A inhibits these HDACs to a similar extent with IC50 of 6 nM, 38 nM, and 8.6 nM, respectively. [2] Trichostatin A (100 ng/mL) treatment induces the expression of transforming growth factor β type II receptor (TβRII) in MIA PaCa-2 cells through the recruitment of p300 and PCAF into a Sp1-NF-Y HDAC complex that binds the DNA element of TβRII promoter, which is associated with a concomitant acetylation of Sp1 and an overall decrease in the amount of HDAC associated with the complex. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
HEK 293NXW4WIJtTnWwY4Tpc44hSXO|YYm=M{i3UFAvP87:TR?=MkTZNlRpM4\qOIV1cGGwb3y=MYHlcohidmOnczDFUoFEKGGlZYT5cIF1cW:wIHHu[EBqdmO{ZXHz[ZMhTU6jQzDhZpVv\GGwY3WgbY4hfGinIITveIFtKGOnbHygcJl{[XSnIHHu[EBifCC2aHWgZ4VtdCC|dYLmZYNmMlrVNlU4QDdyN{m=
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TE13NEnKbHNCeG:ydH;zbZMhSXO|YYm=NGjSXlkxNjQQvF2=M1flNVI1cA>?MojJbY5pcWKrdIOgeIhmKGOnbHygdJJwdGmoZYLheIlwdg>?M2HHS|I2PTd7Nk[1
MEFsMUnGeY5kfGmxbjDBd5NigQ>?NU\NfGUzPc7:TR?=MlLTNVZpNVLCSmJUcW6lcnXhd4V{KHSqZTDFVGVEKGG2dHHjbI1mdnRuIGTpdkBl\WyrdnXyfUBidmRidHjlJIVn\mmlaXXuZ5khd2ZicHXk[ZN1[WxiZn;ycYF1cW:wMnnWNlU1QDJ4M{S=
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PC3 MX\GeY5kfGmxbjDBd5NigQ>?MVewMlHPxE1?MV20PIg>NXqyZY8{TE2VTx?=NVjtcWk3emW4ZYLz[ZMhTU2WNUL2c2RoOjV2M{S5PVc>
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Caco-2 NV3iTG1YTnWwY4Tpc44hSXO|YYm=M37mVlEhyrWPwrC=M2DLblI1KGh?Mona[IVkemWjc3XzJHNGWlRicILveIVqdiCneIDy[ZN{cW:wM4jEPVI{OTl3MEew
HeLaMYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUOxNFAhdk1?M1[4elI1KGh?M2i2bWROW09?MUPJR|UxKG:oIEGwNI5ONH7jRYozOzF4NUe0PC=>
HeLaM4DQUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWP1d5RyPDBibl2=NXrFVlhZPDhiaB?=M1TXfGROW09?M3z5O2lEPTBib3[gOFBvVQ>?MVmyN|E3PTd2OB?=
HeLaM1;SVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1HiN|IxKG6PNXjIUW5DPzJiaB?=NGD5U4NFVVORNYjk[Fd5UUN3MDDv[kAzOG6PNYfrTVhYOjNzNkW3OFg>
HeLaNWnSU5FoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXjBcYg{OTBxM{CvOVAhdk1?MWG3NkBpMlqzSG1UVw>?MUXpcoNz\WG|ZYOgeIhmKG63bXLldkBw\iCPTWCgLO6V|qivKTDsc5N{KGOnbHzzJIRwe2ViZHXw[Y5l\W62bIm=MVuyN|E3PTd2OB?=
MDA-MB-231NF;YVFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoTsNlUuPDByIH7NMkTzOFghcA>?NWLIT5ZEUUN3MDDv[kAzPjNwMn7NxsA>M4e4b|I{ODV3MUm4
MCF-7 NWriOXFFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NF3VOWgzPS12MECgcm0>MnXnOFghcA>?MoXSTWM2OCCxZjCyNlAvPG6PM3L4[FI{ODV3MUm4
ECC-1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHuxXFcyODBibl2=NYL2T|dLOjRiaB?=M2jK[IV1cGGwb3y=NYLIcIpMcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGGyb4D0c5Rq[yCwdXPs[YkhfG9iM{WlMYSyN|AzQDhyMx?=
HEC-1AMVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYOxNFAhdk1?M33t[VI1KGh?M1mxOYV1cGGwb3y=Mnr3bY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJIFxd3C2b4TpZ{BvfWOuZXmgeI8hOzlnMlr3NlMxOjh6MEO=
NHAC-knNEjYWZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4rsWlExNzFyMD:1NFAhdk1?MUmxNkBpMX7EUXNQMUjJR|UxKG:oIEWwNI5OM3Pqb|I{ODF5OEex
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HL60 NGjoO3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2rDeFE2OC1|NUCgcm0>M1rPZ|I1KGh?NX3xS2tvcW6lcnXhd4V{KGOnbHygZZBweHSxc3nzxsB4cGWwIHPvcoNmdnS{YYTpc45{KGirZ3jldkB1cGGwIEK1NEBvVQ>?NVL0VWVMOjJ5NUO3N|k>
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SCC-6NUDTVVAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX6xXohUOjByLUOyNFAhdk1?NIHOeoMyOi9{ND:0PEBpMkXoSG1UVw>?NHfJV5RqdmirYnn0d{B1cGVicILvcIln\XKjdHnvckBw\iCVQ1OtOkBk\WyuczDpckBiKGSxc3WtJIFv\CC2aX3lMYRmeGWwZHXueEBu[W6wZYK=Mm\iNlI2PTJ|MkG=
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... Click to View More Cell Line Experimental Data

In vivo Administration of Trichostatin A at 0.5 mg/kg for 4 weeks displays potent antitumor activity in the N-methyl-N-nitrosourea carcinogen-induced rat mammary carcinoma model, without any measurable toxicity at doses up to 5 mg/kg. [1] Single intraperitoneal doses of 10 mg/kg Trichostatin A in nontransgenic and spinal muscular atrophy (SMA) model mice results in increased levels of acetylated H3 and H4 histones and modest increases in survival motor neuron (SMN) gene expression. Administration of Trichostatin A at 10 mg/kg/day improves survival, attenuates weight loss, and enhances motor behavior in the SMA model mice. [5]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

In vitro HDAC activity Total cellular extracts are prepared from each breast cancer cell line (MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, or SK-BR-3). A 20 μL crude cell extract (~2.5 ×105 cells), in the presence of varying concentrations of Trichostatin A in 0.1% (v/v) ethanol or 0.1% (v/v) ethanol as vehicle control, are incubated for 60 minutes at 25 °C with 1 μL (~1.5 × 106 cpm) of [3H]acetyl-labeled histone H4 peptide substrate (NH2-terminal residues 2-20) that has been acetylated with [3H]acetic acid, sodium salt (3.7 GBq/mmol) by an in vitro incorporation method. Each 200 μL reaction is quenched with 50 μL of 1 M HCl/0.16 M acetic acid and extracted with 600 μL of ethyl acetate, and released [3H]acetate is quantified by scintillation counting. IC50 values are determined graphically using nonlinear regression to fit inhibition data to the appropriate dose-response curve.

Cell Assay:

[1]

Cell lines MCF-7, T-47D, ZR-75-1, BT-474, MDA-MB-231, MDA-MB-453, CAL 51, and SK-BR-3
Concentrations Dissolved in absolute ethanol, final concentrations ~10 μM
Incubation Time 96 hours
Method

Cells are exposed to various concentrations of Trichostatin A for 96 hours. After treatment, cell proliferation is estimated using the sulforhodamine B colorimetric assay. Cell viability is determined by trypan blue exclusion.

Animal Study:

[1]

Animal Models Inbred virgin female (Ludwig/Wistar/Olac) rats bearing tumors induced with NMU
Formulation Dissolved in DMSO
Dosages ~5 mg/kg/day
Administration Injection s.c.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Vigushin DM, et al. Clin Cancer Res, 2001, 7(4), 971-976.

[2] Furumai R, et al. Proc Natl Acad Sci U S A, 2001, 98(1), 87-92.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02486965 Recruiting Fibromyalgia University Hospital, Brest October 2015 --
NCT01954433 Recruiting Glenohumeral Arthritis and/or Rotator Cuff Tear Arthropathy (TSA)|Rotator Cuff Tear (RCR)|Trapeziometacarpal Osteoarthritis (TMC OA) Matthias Flury|Winterthur Institute of Health Economics (  ...more Matthias Flury|Winterthur Institute of Health Economics (WIG), Switzerland|Schulthess Klinik November 2013 --
NCT01575106 Active, not recruiting Pain Massachusetts General Hospital June 2012 --
NCT02762903 Completed Osteoarthritis Columbia University August 2009 --
NCT00914173 Completed Pain Medasense Biometrics Ltd November 2008 --

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Chemical Information

Download Trichostatin A (TSA) SDF
Molecular Weight (MW) 302.4
Formula

C17H22N2O3

CAS No. 58880-19-6
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 23 mg/mL (76.05 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 1% DMSO+30% polyethylene glycol+1% Tween 80, pH 4 6 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R,2E,4E)-6-(4-(dimethylamino)benzoyl)-N-hydroxy-4-methylhepta-2,4-dienamide

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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