Tubastatin-A Chemical Properties

Density 

1.28±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

insoluble in EtOH; insoluble in H2O; ≥10.75 mg/mL in DMSO

form 

solid

pka

8.95±0.10(Predicted)

color 

Off-white to light yellow

InChI

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)

InChIKey

GOVYBPLHWIEHEJ-UHFFFAOYSA-N

SMILES

C(NO)(=O)C1=CC=C(CN2C3=C(C=CC=C3)C3CN(C)CCC2=3)C=C1

Tubastatin-A Usage And Synthesis

Uses

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). Tubastatin A also inhibits HDAC10 and metallo-β-lactamase domain-containing protein 2 (MBLAC2).

Definition

ChEBI: A pyridoindole that is 1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indole which is substituted on the tetrahydropyridine nitrogen by a methyl group and on the indole nitrogen by a p-[N-(hydroxy)aminoca bonyl]benzyl group. It is a histone deacetylase 6 (HDAC6) inhibitor that is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold).

in vivo

target

HDAC6

IC 50

HDAC6: 15 nM (IC₅₀); HDAC8: 854 nM (IC₅₀); HDAC1: 16400 nM (IC₅₀)

References

[1] Kyle V. Butler et al. Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A J. Am. Chem. Soc., 2010, 132 (31), pp 10842-10846 DOI:10.1021/ja102758v
[2] Kozyreva VK, et al. NEDD9 regulates actin dynamics through cortactin deacetylation in an AURKA/HDAC6-dependent manner. Mol Cancer Res. 2014 May;12(5):681-93. DOI:10.1158/1541-7786.MCR-13-0654
[3] de Zoeten EF, et al. Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells. Mol Cell Biol. 2011 May;31(10):2066-78. DOI:10.1128/MCB.05155-11
[4] Brijmohan, Angela, et al. Role of HDAC6 in Transcription Factor EB Mediated Clearance of Misfolded Proteins in Chronic Kidney Disease. University of Toronto.Nov-2017.
[5] Di Fulvio S, et al. Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation. PLoS One. 2011;6(12):e28563 DOI:10.1371/journal.pone.0028563
[6] Ketene AN, et al. Actin filaments play a primary role for structural integrity and viscoelastic response in cells. Integr Biol (Camb). 2012 May;4(5):540-9. DOI:10.1039/c2ib00168c
[7] Lechner S, Malgapo MIP, Gr?tz C, et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target [published online ahead of print, 2022 Apr 28]. Nat Chem Biol. 2022;10.1038/s41589-022-01015-5. DOI:10.1038/s41589-022-01015-5
[8] Géraldy M, Morgen M, Sehr P, et al. Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated. J Med Chem. 2019;62(9):4426-4443. DOI:10.1021/acs.jmedchem.8b01936
[9] Severin Lechner, et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nat Chem Biol. 2022 Apr 28. DOI:10.1038/s41589-022-01015-5

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