WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 403550
CAS#: 1252003-15-8 (free base)
Description: Tubastatin A is a potent and selective HDAC6 inhibitor. Tubastatin A demonstrates 1093-fold selectivity over HDAC1 (IC50 values of 15 nM for HDAC6 vs 16.4 µM for HDAC1). Tubastatin A was substantially more selective than the known HDAC6 inhibitor Tubacin at all isozymes except HDAC8. Tubastatin A is a potent HDAC6 inhibitor with an IC50 value of 15 nM. Comparatively, it demonstrates over 1,000-fold selectivity against all other HDAC isoforms (IC50 >16 μM), excluding HDAC8 (IC50= 0.9 μM). Tubastatin A induces α-tubulin hyperacetylation at 2.5 μM in primary cortical neuron cultures. In a model of oxidative stress induced by glutathione depletion, tubastatin A displays dose-dependent neuronal protection of primary cortical neuron cultures at 5-10 μM.
MedKoo Cat#: 403550
Name: Tubastatin A
CAS#: 1252003-15-8 (free base)
Chemical Formula: C20H21N3O2
Exact Mass: 335.16338
Molecular Weight: 335.4
Elemental Analysis: C, 71.62; H, 6.31; N, 12.53; O, 9.54
Synonym: Tubastatin A
IUPAC/Chemical Name: N-hydroxy-4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzamide
InChi Key: GOVYBPLHWIEHEJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H21N3O2/c1-22-11-10-19-17(13-22)16-4-2-3-5-18(16)23(19)12-14-6-8-15(9-7-14)20(24)21-25/h2-9,25H,10-13H2,1H3,(H,21,24)
SMILES Code: O=C(NO)C1=CC=C(CN2C3=C(CN(C)CC3)C4=C2C=CC=C4)C=C1
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Tubastatin A is a potent and selective HDAC6 inhibitor with an IC50 of 15 nM in a cell-free assay, and is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more).|
|In vitro activity:||Since HDAC6 overexpression seems to contribute importantly to CCA ciliary lost, HDAC6 expression was inhibited with the HDAC6 inhibitor, tubastatin-A. This approaches induced an increase in acetylated-α-tubulin levels, and the restoration of primary cilia expression in the CCA cell lines (3.3 and 18 –fold, respectivelly) (Figure 5A, D, and E); and the restoration of primary cilia correlated with downregulated Hh and MAPK signaling pathways (Figure 5C), as well as decreased cell proliferation rates (decresed in average by 50%) (Figure 5B and F) and invasion (decreased by 40%) (Figure 5G). To analyze if the restoration of cilia is a major reason for these phenotypic changes, the experiments were repeated in KMCH cells stably transfected with IFT88-shRNA to prevent ciliogenesis. In the experiments in which CCA cells were prevented from developing cilia, the proliferation rates and anchorage-independent growth rates were not significantly different from the vehicle-treated cells (Figure 6A and B), showing that the ability of cells to undergo ciliogenesis is essential for the effects of tubastatin-A. Reference: Cancer Res. 2013 Apr 1;73(7):2259-70. doi: 10.1158/0008-5472. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23370327/|
|In vivo activity:||The effect of tubastatin-A was tested using a recently developed syngeneic rat orthotopic model of CCA. Tumors were removed after treatment with tubastatin-A or vehicle for 7 days. The mean tumor weights in animals treated with tubastatin-A was 6-fold lower than vehicle-treated controls (0.33 ± 0.09 vs. 1.81 ± 0.51 g, P<0.05), and the ratios of tumor weight to liver weight and body weight were also significantly reduced (5-and 5.6-fold, respectively) by tubastatin-A treatment (Figure 7A, B, C, D). Furthermore, confocal immunofluorescence microscopy showed a greater frequency of ciliated cholangiocytes in the treated animals compared with controls (29% vs 1.4% ciliated cells per high power field) (Figure 7E, G). Finally, the amount of PCNA positive cells were significantly reduced in the treated tumors compared with vehicle controls (34% vs 65% PCNA positive cells per high power field), indicating decreased proliferation (Figure 7F, H). These data indicate that a drug that inhibits HDAC6 can significantly reduce the growth of CCA in vivo. Reference: Cancer Res. 2013 Apr 1;73(7):2259-70. doi: 10.1158/0008-5472. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23370327/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 335.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, LaRusso NF. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 2013 Apr 1;73(7):2259-70. doi: 10.1158/0008-5472.CAN-12-2938. Epub 2013 Jan 31. PMID: 23370327; PMCID: PMC3768151.|
|In vivo protocol:||1. Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, LaRusso NF. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 2013 Apr 1;73(7):2259-70. doi: 10.1158/0008-5472.CAN-12-2938. Epub 2013 Jan 31. PMID: 23370327; PMCID: PMC3768151. 2. Fu Z, Kong Q, Wu Y, Hu X, Shi J. Effect of Tubastatin A on the Functional Recovery of Cauda Equina Injury in Rats. World Neurosurg. 2018 Jun;114:e35-e41. doi: 10.1016/j.wneu.2018.01.190. Epub 2018 Feb 3. PMID: 29408594.|
1: Kozlov MV, Kleymenova AA, Konduktorov KA, Malikova AZ, Kochetkov SN. Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes. Biochemistry (Mosc). 2014 Jul;79(7):637-42. doi: 10.1134/S0006297914070050. PubMed PMID: 25108326.
2: Zhang Y, Liu CM, Cao XC, Zang Y, Zhou YB, Li J. Involvement of transcription factor XBP1s in the resistance of HDAC6 inhibitor Tubastatin A to superoxidation via acetylation-mediated proteasomal degradation. Biochem Biophys Res Commun. 2014 Jul 18;450(1):433-9. doi: 10.1016/j.bbrc.2014.05.134. Epub 2014 Jun 6. PubMed PMID: 24909686.
3: Zhang L, Liu C, Wu J, Tao JJ, Sui XL, Yao ZG, Xu YF, Huang L, Zhu H, Sheng SL, Qin C. Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice. J Alzheimers Dis. 2014;41(4):1193-205. doi: 10.3233/JAD-140066. PubMed PMID: 24844691.
4: Kozlov MV, Kleĭmenova AA, Konduktorov KA, Kochetkov SN. [New synthesis of highly selective inhibitor of histone deacetylase 6--N-hydroxy-4-(2-methyl-1,2,3,4-tetrahydro-pyrido[4,3b]indol-5-ylmethyl)benzamid e--Tubastatin A]. Bioorg Khim. 2013 Jan-Feb;39(1):117-20. Russian. PubMed PMID: 23844513.
5: Vishwakarma S, Iyer LR, Muley M, Singh PK, Shastry A, Saxena A, Kulathingal J, Vijaykanth G, Raghul J, Rajesh N, Rathinasamy S, Kachhadia V, Kilambi N, Rajgopal S, Balasubramanian G, Narayanan S. Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects. Int Immunopharmacol. 2013 May;16(1):72-8. doi: 10.1016/j.intimp.2013.03.016. Epub 2013 Mar 27. PubMed PMID: 23541634.
6: De Vreese R, Verhaeghe T, Desmet T, D'hooghe M. Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A. Chem Commun (Camb). 2013 May 8;49(36):3775-7. doi: 10.1039/c3cc41422a. Epub 2013 Mar 28. PubMed PMID: 23538448.
7: Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc. 2010 Aug 11;132(31):10842-6. doi: 10.1021/ja102758v. PubMed PMID: 20614936; PubMed Central PMCID: PMC2916045.