File(s) under permanent embargo

Reason: This item is currently closed access.

Targeting Class I Histone Deacetylases in a "Complex" Environment.

journal contribution
posted on 26.07.2018, 11:31 by Christopher J. Millard, Peter J. Watson, Louise Fairall, John W. R. Schwabe
Histone deacetylase (HDAC) inhibitors are proven anticancer therapeutics and have potential in the treatment of many other diseases including HIV infection, Alzheimer's disease, and Friedreich's ataxia. A problem with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Designing isoform-selective inhibitors has proven challenging due to similarities in the structure and chemistry of HDAC active sites. However, the fact that HDACs 1, 2, and 3 are recruited to several large multi-subunit complexes, each with particular biological functions, raises the possibility of specifically inhibiting individual complexes. This may be assisted by recent structural and functional information about the assembly of these complexes. Here, we review the available structural information and discuss potential targeting strategies.

Funding

J.W.R.S. is supported by a Senior Investigator Award (WT100237) from the Wellcome Trust and a Biotechnology and Biological Sciences Research Council Project Grant (BB/J009598/1). J.W.R.S. is a Royal Society Wolfson Research Merit Award Holder.

History

Citation

Trends in Pharmacological Sciences, 2017, 38 (4), pp. 363-377

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Trends in Pharmacological Sciences

Publisher

Elsevier (Cell Press) for Trends

issn

0165-6147

eissn

1873-3735

Acceptance date

21/12/2016

Copyright date

2016

Publisher version

https://www.sciencedirect.com/science/article/pii/S0165614716301936?via=ihub

Notes

The file associated with this record is under a permanent embargo in accordance with the publisher's policy. The full text may be available through the publisher links provided above.

Language

en