Targeting histone deacetylase 8 as a therapeutic approach to cancer and neurodegenerative diseases

• Verfasst von: Chakrabarti, Alokta [VerfasserIn]
• Verfasst von: Witt, Olaf [VerfasserIn]
• Titel: Targeting histone deacetylase 8 as a therapeutic approach to cancer and neurodegenerative diseases
• Verf.angabe: Alokta Chakrabarti, Jelena Melesina, Fiona R Kolbinger, Ina Oehme, Johanna Senger, Olaf Witt, Wolfgang Sippl and Manfred Jung
• Umfang: 26 S.
• Fussnoten: Gesehen am 06.02.2018
• Titel Quelle: Enthalten in: Future medicinal chemistry
• Jahr Quelle: 2016
• Band/Heft Quelle: 8(2016), 13, S. 1609-1634
• ISSN Quelle: 1756-8927
• DOI: doi:10.4155/fmc-2016-0117
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1568137087

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.