HDAC8: a multifaceted target for therapeutic interventions

被引：222

作者：

Chakrabarti, Alokta ^{[1
]}

Oehme, Ina ^{[2
]}

Witt, Olaf ^{[2
,3
]}

Oliveira, Guilherme ^{[4
]}

Sippl, Wolfgang ^{[5
]}

Romier, Christophe ^{[6
]}

Pierce, Raymond J. ^{[7
]}

Jung, Manfred ^{[1
]}

机构：

[1] Univ Freiburg, Inst Pharmaceut Sci, D-79106 Freiburg, Germany

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

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

[4] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Genom & Computat Biol Grp, Belo Horizonte, MG, Brazil

[5] Univ Halle Wittenberg, Inst Pharm, D-06108 Halle, Germany

[6] Univ Strasbourg UDS, CNRS, INSERM, IGBMC,Dept Biol Struct Integrat, Illkirch Graffenstaden, France

[7] Univ Lille, Inst Pasteur Lille, INSERM U1019, CNRS UMR 8204,CIIL, Lille, France

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2015年 / 36卷 / 07期

关键词：

histone deacetylases; HDAC8; Cornelia de Lange syndrome; cancer; schistosoma; X-ray crystallography; HISTONE DEACETYLASE 8; UP-REGULATION; SUBSTRATE-SPECIFICITY; BIOLOGICAL EVALUATION; NEGATIVE REGULATION; GENE-TRANSCRIPTION; LYSINE ACETYLATION; EPIGENETIC CONTROL; CRYSTAL-STRUCTURE; PEPTIDE ARRAYS;

D O I：

10.1016/j.tips.2015.04.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：481 / 492

页数：12

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