1239034-75-3Relevant academic research and scientific papers
HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
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Page/Page column 59, (2011/02/24)
Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.
Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A
Butler, Kyle V.,Kalin, Jay,Brochier, Camille,Vistoli, Guilio,Langley, Brett,Kozikowski, Alan P.
supporting information; experimental part, p. 10842 - 10846 (2010/09/16)
Structure-based drug design combined with homology modeling techniques were used to develop potent inhibitors of HDAC6 that display superior selectivity for the HDAC6 isozyme compared to other inhibitors. These inhibitors can be assembled in a few synthetic steps, and thus are readily scaled up for in vivo studies. An optimized compound from this series, designated Tubastatin A, was tested in primary cortical neuron cultures in which it was found to induce elevated levels of acetylated α-tubulin, but not histone, consistent with its HDAC6 selectivity. Tubastatin A also conferred dose-dependent protection in primary cortical neuron cultures against glutathione depletion-induced oxidative stress. Importantly, when given alone at all concentrations tested, this hydroxamate-containing HDAC6-selective compound displayed no neuronal toxicity, thus, forecasting the potential application of this agent and its analogues to neurodegenerative conditions.
