Histone deacetylase inhibitors: New hope for rheumatoid arthritis?

被引：55

作者：

Choo, Q. Y. ^{[1
]}

Ho, P. C. ^{[1
]}

Lin, H. S. ^{[1
]}

机构：

[1] Natl Univ Singapore, Dept Pharm, Singapore 119260, Singapore

来源：

CURRENT PHARMACEUTICAL DESIGN | 2008年 / 14卷 / 08期

关键词：

epigenetic regulation; histone deacetylase inhibitor; rheumatoid arthritis; growth arrest; pro-inflammatory cytokine; angiogenesis; osteoclastogenesis; nuclear factor kappa-B;

D O I：

10.2174/138161208784007699

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intraarticular formulations.

引用

页码：803 / 820

页数：18

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