Discovery of the First Histone Deacetylase 6/8 Dual Inhibitors

• DOI: 10.1021/jm400390r
• Publication Date: 2013-05-14T21:47:41Z
• Authors: David E. Olson; Florence F. Wagner; Taner Kaya; Jennifer P. Gale; Nadia Aidoud; Emeline L. Davoine; Fanny Lazzaro; Michel Weïwer; Yan-Ling Zhang; Edward B. Holson
• Keywords: HDAC8; HDAC6; Hydroxamic acid; Histone deacetylase 2; HDAC10; HDAC1; Histone deacetylase inhibitor; Histone deacetylase 5; HDAC11

We disclose the first small molecule histone deacetylase (HDAC) inhibitor (3, BRD73954) capable of potently and selectively inhibiting both HDAC6 HDAC8 despite fact that these isoforms belong to distinct phylogenetic classes within HDAC family enzymes. Our data demonstrate meta substituents phenyl hydroxamic acids are readily accommodated upon binding and, furthermore, necessary for potent inhibition HDAC8.