Tubastatin A Hydrochloride

• CAT Number: I001190
• CAS Number: 1310693-92-5
• Molecular Formula: C20H21N3O2.HCl
• Molecular Weight: 371.86
• Purity: ≥95%
• Synonyms: N-hydroxy-4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzamide;hydrochloride
• Target: HDAC
• Solubility: DMSO: ≤ 10.8 mg/mL
• Storage: 3 years -20C powder
• IC50: 15 nM

Tubastatin A Hcl is a potent and selective HDAC6 inhibitor with IC50 of 15 nM; is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more).IC50 Value: 15 nMTarget: HDAC6in 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. At 100 ng/mL Tubastatin A increases Foxp3+ T-regulatory cells (Tregs) suppression of T cell proliferation in vitro. 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. 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.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.

Reference

[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
[2]. Constantin d/’Ydewalle et al. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease Nature Medicine 17, 968-974 (2011)
[3]. 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.
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