Discovery of the First Histone Deacetylase 6/8 Dual Inhibitors

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• 作者：David E. Olson ; Florence F. Wagner ; Taner Kaya ; Jennifer P. Gale ; Nadia Aidoud ; Emeline L. Davoine ; Fanny Lazzaro ; Michel We茂wer ; Yan-Ling Zhang ; Edward B. Holson
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：56
• 期：11
• 页码：4816-4820
• 全文大小：329K
• 年卷期：v.56,no.11(June 13, 2013)
• ISSN：1520-4804

文摘

We disclose the first small molecule histone deacetylase (HDAC) inhibitor (<b>3b>, BRD73954) capable of potently and selectively inhibiting both HDAC6 and HDAC8 despite the fact that these isoforms belong to distinct phylogenetic classes within the HDAC family of enzymes. Our data demonstrate that meta substituents of phenyl hydroxamic acids are readily accommodated upon binding to HDAC6 and, furthermore, are necessary for the potent inhibition of HDAC8.