2. Academic Validation
  3. Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform

Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform

  • J Med Chem. 2013 Sep 26;56(18):7201-11. doi: 10.1021/jm400385r.
Christopher Blackburn 1,  Cynthia Barrett,  Janice Chin,  Kris Garcia,  Kenneth Gigstad,  Alexandra Gould,  Juan Gutierrez,  Sean Harrison,  Kara Hoar,  Chrissie Lynch,  R Scott Rowland,  Chris Tsu,  John Ringeling,  He Xu
Affiliations

Affiliation

  • 1 Discovery, Millennium Pharmaceuticals, Inc. , 40 Landsdowne Street, Cambridge, Massachusetts 02139, United States.
PMID: 23964961 DOI: 10.1021/jm400385r
Abstract

A screen for HDAC6 inhibitors identified acyl derivatives of 4-(aminomethyl)-N-hydroxybenzamide as potent leads with unexpected selectivity over the other subtypes. We designed and synthesized constrained heterocyclic analogues such as tetrahydroisoquinolines that show further enhanced HDAC6 selectivity and inhibitory activity in cellular assays. Selectivity may be attributed to the benzylic spacer more effectively accessing the wider channel of HDAC6 compared to other HDAC subtypes as well as hydrophobic capping groups interacting with the protein surface near the rim of the active site.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-113957
    ≥99.0%, HDAC6 Inhibitor