Discovery of the first histone deacetylase 6/8 dual inhibitors

David Olson, Florence F. Wagner, Taner Kaya, Jennifer P. Gale, Nadia Aidoud, Emeline L. Davoine, Fanny Lazzaro, Michel Weïwer, Yan Ling Zhang, Edward B. Holson

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We disclose the first small molecule histone deacetylase (HDAC) inhibitor (3, 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.

Original languageEnglish (US)
Pages (from-to)4816-4820
Number of pages5
JournalJournal of Medicinal Chemistry
Volume56
Issue number11
DOIs
StatePublished - Jun 13 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Olson, D., Wagner, F. F., Kaya, T., Gale, J. P., Aidoud, N., Davoine, E. L., Lazzaro, F., Weïwer, M., Zhang, Y. L., & Holson, E. B. (2013). Discovery of the first histone deacetylase 6/8 dual inhibitors. Journal of Medicinal Chemistry, 56(11), 4816-4820. https://doi.org/10.1021/jm400390r