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

被引：90

作者：

Chakrabarti, Alokta ^{[1
]}

Melesina, Jelena ^{[2
]}

Kolbinger, Fiona R. ^{[3
]}

Oehme, Ina ^{[3
]}

Senger, Johanna ^{[1
]}

Witt, Olaf ^{[3
,4
]}

Sippl, Wolfgang ^{[2
]}

Jung, Manfred ^{[1
,5
]}

机构：

[1] Univ Freiburg, Inst Pharmaceut Sci, Freiburg, Germany

[2] Univ Halle Wittenberg, Inst Pharm, Halle, Germany

[3] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany

[4] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[5] German Canc Consortium DKTK, Freiburg, Germany

来源：

FUTURE MEDICINAL CHEMISTRY | 2016年 / 8卷 / 13期

关键词：

cancer; druggable; HDAC8; hydroxamic acid; inhibitor; SMC3; stem cell; T-cell; therapy; DE-LANGE-SYNDROME; SMOOTH-MUSCLE DIFFERENTIATION; ISOFORM-SELECTIVE INHIBITORS; SYNDROME SPECTRUM DISORDERS; COHESIN ACETYLATION CYCLE; BIOLOGICAL EVALUATION; HDAC8; INHIBITORS; HYDROXAMIC ACIDS; HEPATOCELLULAR-CARCINOMA; SCHISTOSOMA-MANSONI;

D O I：

10.4155/fmc-2016-0117

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1609 / 1634

页数：26

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