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 Tubastatin A

Tubastatin A is a potent and selective HDAC6 inhibitor. 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 (IC₅₀s >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。

1. 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.