Skip to main content
Journal cover image

Discovery of a fluorescent probe with HDAC6 selective inhibition.

Publication ,  Journal Article
Zhang, Y; Yan, J; Yao, T-P
Published in: Eur J Med Chem
December 1, 2017

There is increasing interest in discovering HDAC6 selective inhibitors as chemical probes to elucidate the biological functions of HDAC6 and ultimately as new therapeutic agents. Small-molecular fluorescent probes are widely used to detect target protein location and function, identify protein complex composition in biological processes of interest. In the present study, structural modification of the previously reported compound 4MS leads to two novel fluorescent HDAC inhibitors, 6a and 6b. Determination of IC50 values against the panel of Zn2+ dependent HDACs (HDAC1-11) reveals that 6b is a HDAC6 selective inhibitor, which can induce hyperacetylation of tubulin but not histone H4. Importantly, fluorescent and immunofluorescent analyses of cells treated with the proteasome inhibitor MG132 demonstrates that 6b can selectively target and image HDAC6 within the inclusion body, the aggresome. These results identify 6b not only as a HDAC6 selective inhibitor but also as a fluorescent probe for imaging HDAC6 and investigating the roles of HDAC6 in various physiological and pathological contexts.

Duke Scholars

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

December 1, 2017

Volume

141

Start / End Page

596 / 602

Location

France

Related Subject Headings

  • Tumor Cells, Cultured
  • Structure-Activity Relationship
  • Molecular Structure
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Histone Deacetylase Inhibitors
  • Histone Deacetylase 6
  • Fluorescent Dyes
  • Drug Discovery
  • Dose-Response Relationship, Drug
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, Y., Yan, J., & Yao, T.-P. (2017). Discovery of a fluorescent probe with HDAC6 selective inhibition. Eur J Med Chem, 141, 596–602. https://doi.org/10.1016/j.ejmech.2017.10.022
Zhang, Yingjie, Jin Yan, and Tso-Pang Yao. “Discovery of a fluorescent probe with HDAC6 selective inhibition.Eur J Med Chem 141 (December 1, 2017): 596–602. https://doi.org/10.1016/j.ejmech.2017.10.022.
Zhang Y, Yan J, Yao T-P. Discovery of a fluorescent probe with HDAC6 selective inhibition. Eur J Med Chem. 2017 Dec 1;141:596–602.
Zhang, Yingjie, et al. “Discovery of a fluorescent probe with HDAC6 selective inhibition.Eur J Med Chem, vol. 141, Dec. 2017, pp. 596–602. Pubmed, doi:10.1016/j.ejmech.2017.10.022.
Zhang Y, Yan J, Yao T-P. Discovery of a fluorescent probe with HDAC6 selective inhibition. Eur J Med Chem. 2017 Dec 1;141:596–602.
Journal cover image

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

December 1, 2017

Volume

141

Start / End Page

596 / 602

Location

France

Related Subject Headings

  • Tumor Cells, Cultured
  • Structure-Activity Relationship
  • Molecular Structure
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Histone Deacetylase Inhibitors
  • Histone Deacetylase 6
  • Fluorescent Dyes
  • Drug Discovery
  • Dose-Response Relationship, Drug