Discovery of the first histone deacetylase 6/8 dual inhibitors.

J Med Chem

Authors	David Olson Florence Wagner Taner Kaya Jennifer Gale Nadia Aidoud Emeline Davoine Fanny Lazzaro Michel Weïwer Yan-Ling Zhang Edward Holson
Keywords	Humans Antineoplastic Agents Histone Deacetylases Repressor Proteins HeLa Cells Protein Binding Structure-Activity Relationship Histone Deacetylase Inhibitors Hydroxamic Acids Molecular Docking Simulation Phthalic Acids Histone Deacetylase 6
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.
Year of Publication	2013
Journal	J Med Chem
Volume	56
Issue	11
Pages	4816-20
Date Published	2013 Jun 13
ISSN	1520-4804
URL
DOI	10.1021/jm400390r
PubMed ID	23672185
Links