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

J Med Chem

Authors	Florence Wagner David Olson Jennifer Gale Taner Kaya Michel Weïwer Nadia Aidoud Méryl Thomas Emeline Davoine Berenice Lemercier Yan-Ling Zhang Edward Holson
Keywords	Humans Histone Deacetylases HeLa Cells Structure-Activity Relationship Isoenzymes Histone Deacetylase Inhibitors Hydroxamic Acids Protein Interaction Domains and Motifs Molecular Mimicry Histone Deacetylase 6
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.
Year of Publication	2013
Journal	J Med Chem
Volume	56
Issue	4
Pages	1772-6
Date Published	2013 Feb 28
ISSN	1520-4804
URL
DOI	10.1021/jm301355j
PubMed ID	23368884
Links