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Trends Pharmacol Sci. 2015 Jul;36(7):481-92. doi: 10.1016/j.tips.2015.04.013. Epub 2015 May 23.

HDAC8: a multifaceted target for therapeutic interventions.

Author information

1
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
2
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
3
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
4
Genomics and Computational Biology Group, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
5
Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
6
Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, Illkirch, France.
7
Center for Infection and Immunity of Lille (CIIL), INSERM U1019 - CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, Lille, France.
8
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany. Electronic address: manfred.jung@pharmazie.uni-freiburg.de.

Abstract

Histone deacetylase 8 (HDAC8) is a class I histone deacetylase implicated as a therapeutic target in various diseases, including cancer, X-linked intellectual disability, and parasitic infections. It is a structurally well-characterized enzyme that also deacetylates nonhistone proteins. In cancer, HDAC8 is a major 'epigenetic player' that is linked to deregulated expression or interaction with transcription factors critical to tumorigenesis. In the parasite Schistosoma mansoni and in viral infections, HDAC8 is a novel target to subdue infection. The current challenge remains in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors. Here, we review HDAC8 as a drug target and discuss inhibitors with respect to their structural features and therapeutic interventions.

KEYWORDS:

Cornelia de Lange syndrome; HDAC8; X-ray crystallography; cancer; histone deacetylases; schistosoma

PMID:
26013035
DOI:
10.1016/j.tips.2015.04.013
[Indexed for MEDLINE]
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