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J Med Chem DOI:10.1021/jm301355j

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

Publication TypeJournal Article
Year of Publication2013
AuthorsWagner, FF, Olson, DE, Gale, JP, Kaya, T, Weïwer, M, Aidoud, N, Thomas, M, Davoine, EL, Lemercier, BC, Zhang, Y-L, Holson, EB
JournalJ Med Chem
Date Published2013 Feb 28
KeywordsHeLa Cells, Histone Deacetylase 6, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Isoenzymes, Molecular Mimicry, Protein Interaction Domains and Motifs, Structure-Activity Relationship

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.


Alternate JournalJ. Med. Chem.
PubMed ID23368884