Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif

  • J Med Chem. 2013 Feb 28;56(4):1772-6. doi: 10.1021/jm301355j.
Florence F Wagner  1 ,  David E Olson ,  Jennifer P Gale ,  Taner Kaya ,  Michel Weïwer ,  Nadia Aidoud ,  Méryl Thomas ,  Emeline L Davoine ,  Bérénice C Lemercier ,  Yan-Ling Zhang ,  Edward B Holson
Affiliations
  • 1. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
PMID: 23368884 DOI: 10.1021/jm301355j
Abstract

Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117554
    BRD9757
    99.75%, HDAC6 inhibitor
    target: HDAC
    Research Areas: Cancer