Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

Journal Article · Wed Nov 20 00:00:00 EST 2013 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmc.2011.06.030· OSTI ID:1025628

Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis ^[1]

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1. Novartis

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: INDUSTRY
• OSTI ID: 1025628
• Journal Information: Bioorg. Med. Chem. Lett., Vol. 19, Issue (15) ; 08, 2011; ISSN 0968-0896
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ACETATES
CRYSTALLOGRAPHY
HISTONES
HYPOTHESIS
SIMULATION