Tubastatin A 

Tubastatin A (GMP) is the Tubastatin A (HY-13271A) produced by using GMP guidelines. GMP small molecules work appropriately as an auxiliary reagent for cell therapy manufacture. 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).

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 CC12 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Daily treatment of Tubastatin A at 0.5 mg/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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

335.40

C₂₀H₂₁N₃O₂

1252003-15-8

O=C(NO)C1=CC=C(CN2C3=C(CN(C)CC3)C4=C2C=CC=C4)C=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Lechner S, Malgapo MIP, Grätz 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.  [Content Brief]

  [2]. 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.  [Content Brief]

  [3]. Severin Lechner, et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nat Chem Biol. 2022 Apr 28.  [Content Brief]

  [4]. 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.  [Content Brief]

  [5]. 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.

  [6]. 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  [Content Brief]

  [7]. 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.  [Content Brief]

  [8]. Di Fulvio S, et al. Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation. PLoS One. 2011;6(12):e28563  [Content Brief]

  [9]. 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.  [Content Brief]