Potent and Selective Inhibition of Histone Deacetylase 6 (HDAC6) Does Not Require a Surface-Binding Motif

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• 作者：Florence F. Wagner ; David E. Olson ; Jennifer P. Gale ; Taner Kaya ; Michel We茂wer ; Nadia Aidoud ; M茅ryl Thomas ; Emeline L. Davoine ; B茅r茅nice C. Lemercier ; Yan-Ling Zhang ; Edward B. Holson
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：February 28, 2013
• 年：2013
• 卷：56
• 期：4
• 页码：1772-1776
• 全文大小：281K
• 年卷期：v.56,no.4(February 28, 2013)
• ISSN：1520-4804

文摘

Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound <b>14b> (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure鈥揳ctivity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.