Tubastatin A HCl

For research use only.

Catalog No.S2627 Synonyms: TSA HCl

30 publications

Tubastatin A HCl Chemical Structure

CAS No. 1310693-92-5

Tubastatin A HCl (TSA) is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more).

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Selleck's Tubastatin A HCl has been cited by 30 publications

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Biological Activity

Description Tubastatin A HCl (TSA) is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more).
Targets
HDAC6 [1]
(Cell-free assay)
HDAC8 [1]
(Cell-free assay)
15 nM 854 nM
In vitro

Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. In homocysteic acid (HCA) induced neurodegeneration assays, Tubastatin A displays dose-dependent protection against HCA-induced neuronal cell death starting at 5 μM with near complete protection at 10 μM. [1] At 100 ng/mL Tubastatin A increases Foxp3+ T-regulatory cells (Tregs) suppression of T cell proliferation in vitro. [2] Tubastatin A treatment in C2C12 cells would lead to myotube formation impairment when alpha-tubulin is hyperacetylated early in the myogenic process; however, myotube elongation occurs when alpha-tubulin is hyeperacetylated in myotubes. [3] A recent study indicates that Tubastatin A treatment increases cell elasticity as revealed by atomic force microscopy (AFM) tests without exerting drastic changes to the actin microfilament or microtubule networks in mouse ovarian cancer cell lines, MOSE-E and MOSE-L. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
neuron cultures NFjOTVdMcW6jc3WgZZN{[Xl? NUXBdXhPOi53IN88US=> NFjRSoJFVVOR MYTpcoR2[2W|IN8xMZR2[nWuaX6gbJlx\XKjY3X0fYxifGmxbh?= M{jV[FIxPjF2OUO2
neuron cultures M13EUmZ2dmO2aX;uJIF{e2G7 MoXiglExKM7:TR?= MnHUSG1UVw>? MVvwdo91\WO2czDh[4FqdnO2IHfseZRifGirb37lJIRmeGyndHnvck1qdmS3Y3XkJI95cWSjdHn2[UB{fHKnc4O= MnzpNlA3OTR7M{[=
134/04 MkO4SpVv[3Srb36gZZN{[Xl? MXW3MlUhyrWP M2HYPIlueGGrcoOgcZlwfHWkZTDmc5Ju[XSrb36= NULnSFdHOjJzN{S4N|k>
C2C12 NWrCfmFZTnWwY4Tpc44h[XO|YYm= NIfyZmQ4NjViwsXN MnPKbY1x[Wm{czDtfY91fWKnIH\vdo1ifGmxbh?= MoH2NlIyPzR6M{m=
HaCaT keratinocytes MmLaSpVv[3Srb36gZZN{[Xl? MmDoNVAh|ryP MWTicI9kc3NiYYLz[Y5qfGViZoLvcUBqdmS3Y3nu[{BPemZ{IIDyc5RmcW5idILhcpNt[XSrb36= MkS3NlI{Pjd4OEm=
JURL-MK1 NX7qV4xtTnWwY4Tpc44h[XO|YYm= NH\IZokyOCEQvF2= M2j4fIVvcGGwY3XzJINmdGxiYXTo[ZNqfmm2eTD0c{BncWK{b37lZ5Rqdg>? M{PC[|I{ODJ{NUiz
CML-T1 NY\aNWhSTnWwY4Tpc44h[XO|YYm= MlXKNVAh|ryP NI[1fVlmdmijbnPld{Bk\WyuIHHkbIV{cX[rdImgeI8h\mmkcn;u[YN1cW5? MofDNlMxOjJ3OEO=
K562 M4H1SWZ2dmO2aX;uJIF{e2G7 MYKxNEDPxE1? NEXNNmhmdmijbnPld{Bk\WyuIHHkbIV{cX[rdImgeI8h\mmkcn;u[YN1cW5? NGfudFczOzB{MkW4Ny=>
HL-60 NGrqcGFHfW6ldHnvckBie3OjeR?= M{mw[lExKM7:TR?= Mnrh[Y5p[W6lZYOgZ4VtdCCjZHjld4l3cXS7IITvJIZq[nKxbnXjeIlv M3LEUlI{ODJ{NUiz
KMCH MYjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M2H0[54yOCEQvF2= M2Pyd4Rm[3KnYYPld{Bxem:uaX\ldoF1cW:wIHHu[EBidmOqb4Lh[4UucW6mZYDlcoRmdnRiZ4Lve5Rp NYTuVXBjOjN|N{CzNlc>
THP-1 NUjY[GJnTnWwY4Tpc44h[XO|YYm= MmXGglExKM7:TR?= MlXSbY5pcWKrdIOgWG5HNc7zIHHu[EBKVC14IIPlZ5JmfGmxbh?= M3rjOlI{PTRzNkO0
RAW 264.7 NGT1fnlHfW6ldHnvckBie3OjeR?= MY\+NVAh|ryP NF\re5JifHSnboXheIV{KE6RIIDyc4R2[3Srb36= M2\RSFI{PTRzNkO0
HT3 M1;4T2Z2dmO2aX;uJIF{e2G7 MWD+OUDPxE1? M{ezZWROW09? M{LTZ4lv\HWlZYOgeIhmKGSrZn\ldoVvfGmjbDFOtU11fWK3bHnuJIFk\XS7bHH0bY9v MUCyN|Y6QDR4OB?=
SiHa NYq2XnU3TnWwY4Tpc44h[XO|YYm= NF\aXXp,PSEQvF2= NGjXSI9FVVOR MVPpcoR2[2W|IITo[UBlcW[oZYLlcpRq[WxizsGteJVjfWyrbjDhZ4V1gWyjdHnvci=> MlrUNlM3QTh2Nki=
CaSki NY\yXZJvTnWwY4Tpc44h[XO|YYm= MWD+OUDPxE1? MXjEUXNQ M1HB[Ylv\HWlZYOgeIhmKGSrZn\ldoVvfGmjbDFOtU11fWK3bHnuJIFk\XS7bHH0bY9v MXmyN|Y6QDR4OB?=
SiHa M4HPVmZ2dmO2aX;uJIF{e2G7 NXzW[XZwhjVizszN NUjwSlZNTE2VTx?= NWi2R|E4cW6qaXLpeJMhXGijcIPp[4Fz\2mwLTDvdkBGT0ZvaX7keYNm\CCVT1PFJIFkfGm4YYTpc44> MXeyN|Y6QDR4OB?=
CaSki MmnDSpVv[3Srb36gZZN{[Xl? MYH+OUDPxE1? NWTlN2pvTE2VTx?= NE\FWGJqdmirYnn0d{BVcGGyc3nnZZJocW5vIH;yJGVITi2rbnT1Z4VlKFORQ1WgZYN1cX[jdHnvci=> NUXXZmxkOjN4OUi0Olg>
MCF-7 MUjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NY\ZWm9[OzBizszN MWPEUXNQ M4HZOmlEPTB;MUWg{txO Mm\SNlM4QTh4OEC=
MCF-7 MluxSpVv[3Srb36gZZN{[Xl? NFjlS|M{OCEQvF2= NV;ESmk2TE2VTx?= M3K3VIlv[3KnYYPld{B1cGVibXnjdo91fWK3bHWgZYNmfHmuYYTpc44hdGW4ZXyu NYHUU3ltOjN5OUi2PFA>
MCF-7 NIHZRo5HfW6ldHnvckBie3OjeR?= MXWzNEDPxE1? NVLqeYtyTE2VTx?= M3H3Z5N1[WKrbHn6[ZMhdWmlcn;0eYJ2dGW|IHHnZYlve3RiY3;s[E1qdmS3Y3XkJIRmeG:ueX3ldol7[XSrb36= MnH3NlM4QTh4OEC=
MCF-7 M3vKZWZ2dmO2aX;uJIF{e2G7 MUexOUDPxE1? NEnRTJBFVVOR MoLRd5Ri[mmuaYrld{BucWO{b4T1ZpVt\XNiYXfhbY5{fCCwb3Pv[IF7d2ynLXnu[JVk\WRiZHnzZZN{\W2kbIm= M3L3VlI{Pzl6Nkiw
MCF-7 MljhSpVv[3Srb36gZZN{[Xl? NVfIb4pGOzBizszN MmH2SG1UVw>? MkHkZYx1\XKnczD0bIUh[XO|ZX3icJkh\HmwYX3pZ5Mhd2ZiaX70[ZJxcGG|ZTDtbYNzd3S3YoXs[ZM> NWXqeWtTOjN5OUi2PFA>
MCF-7 M{\IdWZ2dmO2aX;uJIF{e2G7 NUDqRlF[OzBizszN NIjMVINFVVOR NVHuS49ncW6lcnXhd4V{KHSqZTDibY5lcW6pIH;mJGhFSUN4IIfpeIghcW62ZYLwbIF{\SCvaXPyc5R2[nWuZYO= MVyyN|c6QDZ6MB?=
PC12 M{[w[WZ2dmO2aX;uJIF{e2G7 MnHSglMh|ryP M{KzXGROW09? MYH1dE1z\We3bHH0[ZMh[W62aT3vfIll[XSrdnWg[4Vv\SCneIDy[ZN{cW:wIILlcIF1\WRidH:geJJidnOlcnnweIlwdiCoYXP0c5IhYEKSMYO= MmK1NlQ6ODl4OE[=
PC12 NUi2VoVLT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MV3+N{DPxE1? NYjEfm9VTE2VTx?= NWnUZZdremW4ZYLz[UBJOk9{LXnu[JVk\WRiZ4Lve5RpKGmwaHnibZRqd25? M3P2eVI1QTB7Nki2
HEK293T NXnlToxITnWwY4Tpc44h[XO|YYm= MX\+N{DPxE1? Ml\qSG1UVw>? NVHwc25{fXBvcnXneYxifGWmIGjCVFF{KHC{b4TlbY4hdGW4ZXy= Mo[wNlQ6ODl4OE[=
HEK293T M2m4fGZ2dmO2aX;uJIF{e2G7 NWTyZndmhjNizszN M4[2WmROW09? NES5eXFl\WyjeYOgXGJROXNicILveIVqdiCmZXfyZYRifGmxbjD2bYEh[WOndInsZZRqd25vbXXkbYF1\WRicILveIVie2:vYXyg[IVoemGmYYTpc44> MnXZNlQ6ODl4OE[=
Huh7 NF7NSm9HfW6ldHnvckBie3OjeR?= NWPuelZmhjVizszN NFTDPZhFVVOR NWfzZ5VHe3WycILld5NmeyCycn;sbYZmemG2aX;uJI9nKGincHH0bZRqeyCFII\pdpV{KHKncHzpZ49vKHerdHigSWM2OCB;IECuN{DPxE1? MknoNlUyODh|Mk[=
SKMEL21 Mn30S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MkSzglUxOCCwTR?= NXHEUZlnTE2VTx?= NXj2fVhvcW6qaXLpeJMh[2WubDDwdo9tcW[ncnH0bY9v Mk\zNlU6PTd6MUK=
SKMEL103 MoXlS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NFjze41,PTByIH7N NYX1SYc1TE2VTx?= MYnpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= MXiyOVk2PzhzMh?=
SKMEL28 NISwbYxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NFj1SZV,PTByIH7N NUX3[Hd7TE2VTx?= M{T6UYlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=> M1fw[lI2QTV5OEGy
WM164 NID1UIVIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M1vySJ42ODBibl2= Ml;OSG1UVw>? MXjpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= MV[yOVk2PzhzMh?=
WM1361a M4[5eGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MXT+OVAxKG6P M{\k[GROW09? MlnkbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;u M4jFeFI2QTV5OEGy
WM1366 MVjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NEjaOGl,PTByIH7N NGjBWmxFVVOR MYHpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= NIfle3QzPTl3N{ixNi=>
WM793 MVzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MV7+OVAxKG6P MUXEUXNQ M4\2TYlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=> MoHaNlU6PTd6MUK=
WM35 NWXoelZHT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NXzDVHk2hjVyMDDuUS=> MlLvSG1UVw>? MXzpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= M{Kxd|I2QTV5OEGy
WM983a MkTTS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NXjlbXlHhjVyMDDuUS=> NEW2SpVFVVOR NGP4[JZqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44> NH22TZozPTl3N{ixNi=>
WM793 MkTzSpVv[3Srb36gZZN{[Xl? NUTSNHNHhjZizszN M1HReGROW09? NH65UXNqdmS3Y3WgS|Eh[XK{ZYP0 MmrQNlU6PTd6MUK=
WM164 NWjuTHhETnWwY4Tpc44h[XO|YYm= MlTFglYh|ryP NVKyZo55TE2VTx?= MmDqbY5lfWOnIFexJIFzemW|dB?= MUWyOVk2PzhzMh?=
WM983a Mor6SpVv[3Srb36gZZN{[Xl? NHHtcJR,PiEQvF2= MVLEUXNQ MWrpcoR2[2ViR{GgZZJz\XO2 MYSyOVk2PzhzMh?=
WM164 M1:4bmZ2dmO2aX;uJIF{e2G7 MVH+N{DPxE1? MluwSG1UVw>? M1;4V4F2\22nboTzJIV5eHKnc4Ppc44hd2ZiTVjDJINt[XO|IFmgZY5lKG2nbHHuc41iKGG|c3;jbYF1\WRiYX70bYdmdnN? NW\GeY5iOjV7NUe4NVI>
WM983a MYPGeY5kfGmxbjDhd5NigQ>? MWL+N{DPxE1? M{jVbmROW09? NVe1c5dZ[XWpbXXueJMh\XiycnXzd4lwdiCxZjDNTGMh[2yjc4OgTUBidmRibXXsZY5wdWFiYYPzc4Nq[XSnZDDhcpRq\2Wwcx?= NV;rOG4xOjV7NUe4NVI>
IPC298 Ml\qSpVv[3Srb36gZZN{[Xl? NUDjc4FZhjNizszN NXXvNlJJTE2VTx?= MmixZZVodWWwdIOg[ZhxemW|c3nvckBw\iCPSFOgZ4xie3NiSTDhcoQhdWWuYX7vcYEh[XO|b3PpZZRm\CCjboTp[4Vvew>? MVqyOVk2PzhzMh?=
SKMEL30 MVLGeY5kfGmxbjDhd5NigQ>? NY\WPWlshjNizszN MnztSG1UVw>? M1vPdoF2\22nboTzJIV5eHKnc4Ppc44hd2ZiTVjDJINt[XO|IFmgZY5lKG2nbHHuc41iKGG|c3;jbYF1\WRiYX70bYdmdnN? NH:xRoUzPTl3N{ixNi=>
TCa83 MWrGeY5kfGmxbjDhd5NigQ>? MWTpcoR2[2W|IGDUSW4h\XiycnXzd4lwdiCjbnSgcYVu[nKjbnWgeJJidnOub3PheIlwdg>? NUHuXmdSOjZ{N{mzNFM>
293T NFOxdJhHfW6ldHnvckBie3OjeR?= MnLrglIh|rypL33s M2jMcYlv\HWlZYOgVHRGViCneIDy[ZN{cW:wIHHu[EBu\W2kcnHu[UB1emGwc3zvZ4F1cW:w NUnGW2d7OjZ{N{mzNFM>
SACC-83 MWHGeY5kfGmxbjDhd5NigQ>? NVfKenlFhjJizsznM41t NHvhclNqdmS3Y3XzJHBVTU5iZYjwdoV{e2mxbjDhcoQhdWWvYoLhcoUhfHKjboPsc4NifGmxbh?= Mn2xNlYzPzl|MEO=
293T MVPGeY5kfGmxbjDhd5NigQ>? MoT0glIh|rypL33s MWLpcoR2[2W|IGDUSW4h[WOndInsZZRqd25iYYSgT|E3Ow>? MoPGNlYzPzl|MEO=
U-87 MG M3W3bWZ2dmO2aX;uJIF{e2G7 M4LHc54zKM7:Zz;tcC=> MX3pcohq[mm2czD0bIUhdWmpcnH0bY9vKGGwZDDpcpZie2mxbh?= M4LielI3Ojd7M{Cz
U-87 MG NV;WbnlsTnWwY4Tpc44h[XO|YYm= MmDnglExKM7:TR?= NGLYS3dqdmirYnn0d{BCU1RicHjvd5Bpd3K7bHH0bY9v MYWyOlI4QTNyMx?=
U-87 MG M3nTbWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NXWwbpdShjFyIN88US=> NX;LRYhCcW6qaXLpeJMh[2WubDDndo94fGh? MoHzNlYzPzl|MEO=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
EGFR / p-AKT / AKT / p-ERK / ERK ; 

PubMed: 29665050     


In KYSE140 (C) and KYSE180 (D), Tubastatin treatment EGFR, AKT, phospho-AKT and phospho-ERK levels were decreased in tubastatin-treated cells compared with control group.

29665050
Immunofluorescence
α-tubulin / Acetylated tubulin ; 

PubMed: 23798680     


Effects of tubastatin A on microtubules and microtubule acetylation level are shown. MCF-7 cells were treated with different concentrations of tubastatin A for 24 h and processed for immunostaining with antibodies against α-tubulin (green) and acetylated tubulin (red). Scale bars, 10 μm.

HDAC6; 

PubMed: 23798680     


MCF-7 cells are treated with vehicle, 30 μm tubastatin A (TBA), or 240 nm TSA for 24 h and fixed and processed to visualize microtubules (red) and HDAC6 (green). Scale bar, 20 μm.

23798680
In vivo Daily treatment of Tubastatin A at 0.5mg/kg inhibits HDAC6 to promote Tregs suppressive activity in mouse models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully major histocompatibility complex (MHC)-incompatible cardiac allograft rejection. [2]

Protocol

Kinase Assay:[1]
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Enzyme Inhibition Assays:

Enzyme inhibition assays are performed by the Reaction Biology Corporation, Malvern, PA, using the Reaction Biology HDAC Spectrum platform. (www.reactionbiology.com) The HDAC1, 2, 4, 5, 6, 7, 8, 9, 10, and 11 assays use 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. Tubastatin A is 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 Research:[1]
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  • Cell lines: Primary cortical neuron of fetal Sprague-Dawley rats (embryonic day 17)
  • Concentrations: 0-10 μM
  • Incubation Time: 24 hours
  • Method: Primary cortical neuron cultures are obtained from the cerebral cortex of fetal Sprague-Dawley rats (embryonic day 17) as described previously. All experiments are initiated 24 hours after plating. Under these conditions, the cells are not susceptible to glutamate-mediated excitotoxicity. For cytotoxicity studies, cells are rinsed with warm PBS and then placed in minimum essential medium (Invitrogen) containing 5.5 g/L glucose, 10% fetal calf serum, 2 mM L-glutamine, and 100 μM cystine. Oxidative stress is induced by the addition of the glutamate analogue homocysteate (HCA; 5 mM) to the media. HCA is diluted from 100-fold concentrated solutions that are adjusted to pH 7.5. In combination with HCA, neurons are treated with Tubastatin A at the indicated concentrations. Viability is assessed after 24 hours by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method.
    (Only for Reference)
Animal Research:[2]
- Collapse
  • Animal Models: Na?ve CD45RBhi CD4+ CD25- cells (1 × 106) from WT or HDAC6-/- mice Are injected i.p. into B6/Rag1-/-mice.
  • Dosages: 0.5 mg/kg
  • Administration: Tubastatin A is injected i.p. daily.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 74 mg/mL (198.99 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5%DMSO+40%PEG300+5%Tween80+50%ddH2O
For best results, use promptly after mixing.
5.5 mg/mL

* 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 Information

Molecular Weight 371.86
Formula

C20H21N3O2.HCl

CAS No. 1310693-92-5
Storage powder
in solvent
Synonyms TSA HCl
Smiles CN1CCC2=C(C1)C3=CC=CC=C3N2CC4=CC=C(C=C4)C(=O)NO.Cl

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID