2. Academic Validation
  3. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

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

  • Bioorg Med Chem. 2011 Aug 1;19(15):4626-34. doi: 10.1016/j.bmc.2011.06.030.
Lewis Whitehead 1,  Markus R Dobler,  Branko Radetich,  Yanyi Zhu,  Peter W Atadja,  Tavina Claiborne,  Jonathan E Grob,  Andrew McRiner,  Margaret R Pancost,  Anup Patnaik,  Wenlin Shao,  Michael Shultz,  Ritesh Tichkule,  Ruben A Tommasi,  Brian Vash,  Ping Wang,  Travis Stams
Affiliations

Affiliation

  • 1 Novartis Institutes for Biomedical Research, 100 Technology Square & 250 Massachusetts Avenue, Cambridge, MA 02139, USA. lewis.whitehead@novartis.com
PMID: 21723733 DOI: 10.1016/j.bmc.2011.06.030
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.

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