Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif

Florence F. Wagner, David Olson, Jennifer P. Gale, Taner Kaya, Michel Weïwer, Nadia Aidoud, Méryl Thomas, Emeline L. Davoine, Bérénice C. Lemercier, Yan Ling Zhang, Edward B. Holson

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (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-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.

Original languageEnglish (US)
Pages (from-to)1772-1776
Number of pages5
JournalJournal of Medicinal Chemistry
Volume56
Issue number4
DOIs
StatePublished - Mar 11 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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  • Cite this

    Wagner, F. F., Olson, D., Gale, J. P., Kaya, T., Weïwer, M., Aidoud, N., Thomas, M., Davoine, E. L., Lemercier, B. C., Zhang, Y. L., & Holson, E. B. (2013). Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif. Journal of Medicinal Chemistry, 56(4), 1772-1776. https://doi.org/10.1021/jm301355j