title: Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors.
abstract: Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.
authors: Novartis Institutes for Biomedical Research, 100 Technology Square & 250 Massachusetts Avenue, Cambridge, MA 02139, USA. lewis.whitehead@novartis.com
authors: Lewis
authors: L
authors: Whitehead
authors: Markus R
authors: MR
authors: Dobler
authors: Branko
authors: B
authors: Radetich
authors: Yanyi
authors: Y
authors: Zhu
authors: Peter W
authors: PW
authors: Atadja
authors: Tavina
authors: T
authors: Claiborne
authors: Jonathan E
authors: JE
authors: Grob
authors: Andrew
authors: A
authors: McRiner
authors: Margaret R
authors: MR
authors: Pancost
authors: Anup
authors: A
authors: Patnaik
authors: Wenlin
authors: W
authors: Shao
authors: Michael
authors: M
authors: Shultz
authors: Ritesh
authors: R
authors: Tichkule
authors: Ruben A
authors: RA
authors: Tommasi
authors: Brian
authors: B
authors: Vash
authors: Ping
authors: P
authors: Wang
authors: Travis
authors: T
authors: Stams
mesh_terms: D019342:Acetic Acid / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D056572:Histone Deacetylase Inhibitors; D020033:Protein Isoforms; D006655:Histone Deacetylases; D019342:Acetic Acid