Targeting histone deacetylase 8 as a therapeutic approach to cancer and neurodegenerative diseases
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 expres...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 August 2016
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| In: |
Future medicinal chemistry
Year: 2016, Volume: 8, Issue: 13, Pages: 1609-1634 |
| ISSN: | 1756-8927 |
| DOI: | 10.4155/fmc-2016-0117 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.4155/fmc-2016-0117 Verlag, Volltext: https://www.future-science.com/doi/10.4155/fmc-2016-0117 
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| Author Notes: | Alokta Chakrabarti, Jelena Melesina, Fiona R Kolbinger, Ina Oehme, Johanna Senger, Olaf Witt, Wolfgang Sippl and Manfred Jung |
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| 520 | |a 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. | ||
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