Review
HDAC8: a multifaceted target for therapeutic interventions

https://doi.org/10.1016/j.tips.2015.04.013Get rights and content
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Highlights

  • HDAC8, a unique class I HDAC, recognizes both histone and nonhistone substrates.

  • HDAC8 is implicated in cancer, schistosomiasis, and Cornelia de Lange syndrome.

  • Structural specificities of HDAC8 allow the design of selective inhibitors.

  • Drug development is underway to combat diseases linked with HDAC8.

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

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

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