In:
Future Medicinal Chemistry, Future Science Ltd, Vol. 8, No. 13 ( 2016-09), p. 1609-1634
Abstract:
Histone deacetylase 8 (HDAC8), a unique class I zinc-dependent HDAC, is an emerging target in cancer and other diseases. Its substrate repertoire extends beyond histones to many nonhistone proteins. Besides being a deacetylase, HDAC8 also mediates signaling via scaffolding functions. Aberrant expression or deregulated interactions with transcription factors are critical in HDAC8-dependent cancers. Many potent HDAC8-selective inhibitors with cellular activity and anticancer effects have been reported. We present HDAC8 as a druggable target and discuss inhibitors of different chemical scaffolds with cellular effects. Furthermore, we review HDAC8 activators that revert activity of mutant enzymes. Isotype-selective HDAC8 targeting in patients with HDAC8-relevant cancers is challenging, however, is promising to avoid adverse side effects as observed with pan-HDAC inhibitors.
Type of Medium:
Online Resource
ISSN:
1756-8919
,
1756-8927
DOI:
10.4155/fmc-2016-0117
Language:
English
Publisher:
Future Science Ltd
Publication Date:
2016
SSG:
15,3
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