Tubastatin A, Hydrochloride Salt, >99%

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• Tubastatin A is a histone deacetylase (HDAC) 6 inhibitor. It inhibited HDAC6 with an IC50 of 15 nM, also inhibited HDAC1 (IC50 = 16.4 μM) and HDAC8 (IC50 = 0.85 μM), but not other HDACs (IC50 > 30 μM). It induced the acetylation of [alpha]-tubulin and protected primary cortical neurons against glutathione depletion-induced oxidative stress. Butler K.V., et al. "Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A." J. Am. Chem. Soc. 132: 10842-10846 (2010).
• Tubastatin A restored the expression of primary cilia in cholangiocarcinoma cell lines, decreased cell proliferation, and inhibited anchorage-independent growth. These effects of tubastatin A were blocked by stable transfection of IFT88-shRNA, which prevented cholangiocarcinoma cells from regenerating cilia. Tubastatin A also inhibited the tumor growth in a cholangiocarcinoma animal model. Gradilone S.A., et al. "HDAC6 inhibition restores ciliary expression and decreases tumor growth." Cancer Res. 73: 2259-2270 (2013).
• HDAC6 inhibition either by HDAC6 knockout or with tubastatin A promoted Foxp3(+) T-regulatory cell inhibitory activity in models of inflammation and autoimmunity. It blocked the development and progression of murine colitis and prevented allograft rejection in mice. de Zoeten E.F., et al. "Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells." Mol. Cell Biol. 31: 2066-2078 (2011).
• Related CAS numbers: 1239262-52-2 for the TFA salt; 1252003-15-8 for the free base.
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• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
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