Pharmacological inhibition a of histone deacetylases for the treatment of cancer, neurodegenerative disorders and inflammatory diseases

被引:8
|
作者
Bonfils, Claire [1 ]
Walkinshaw, Donald R. [2 ,3 ]
Besterman, Jeffrey M. [1 ]
Yang, Xiang-Jiao [2 ,3 ]
Li, Zuomei [1 ]
机构
[1] MethylGene Inc, Montreal, PQ H4S 2A1, Canada
[2] McGill Univ, Dept Med, Ctr Hlth, Mol Oncol Grp, Montreal, PQ, Canada
[3] McGill Univ, McGill Canc Ctr, Montreal, PQ, Canada
基金
美国国家卫生研究院;
关键词
belinostat; clinical development; HDAC; HDAC inhibitors; inflammatory diseases; MGCD0103; neurodegenerative diseases; oncology; panobinostat; romidepsin; SNDX-275; vorinostat;
D O I
10.1517/17460441.3.9.1041
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Histone deacetylases (HDACs) constitute a family of enzymes that deacetylate histones and other cellular proteins. They are major regulators of transcription and are also important in other cellular processes. Objective: The review provides an updated summary of HDAC pharmacological inhibition in clinical oncology, as well as in preclinical studies on inflammation and neurodegenerative diseases. Resultskonclusion: HDAC inhibition is a validated approach in cancer therapy, as evidenced by the approval of vorinostat and by encouraging clinical data from various HDAC inhibitors. Moreover, preclinical proof-of-concept studies are emerging from animal models for non-oncologic diseases, including inflammatory and neurodegenerative diseases. The identification of the appropriate target spectrum and the development of class- or isotype-selective inhibitors will be central events in the future.
引用
收藏
页码:1041 / 1065
页数:25
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