期刊
CURRENT PHARMACEUTICAL DESIGN
卷 14, 期 6, 页码 545-561出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161208783885317
关键词
-
Histone deacetylases ( HDACs) are one of two counteracting enzyme families whose activity controls the acetylation state of lysine protein residues, notably those contained in the N-terminal extensions of the core histones. Deregulation of the acetylation state of specific lysine residues has been implicated in a multitude of biologic processes, notably cancer, where HDACs are known to be involved in the control of cell cycle progression, cell survival and differentiation. HDAC inhibitors are being developed as anti-neoplastic agents. Nature has led the way in the development of these compounds, with trichostatin A being the first hydroxamic acid HDAC inhibitor identified. Likewise, the disulfide depsipeptide Romidepsin is currently in clinical trials, while an array of cyclic tetrapeptides HDAC inhibitors have been reported. Rational drug design has allowed these cyclic tetrapeptide to be transformed into equally potent small molecule inhibitors selective for either class I or class II HDACs. While acyclic alkyl ketones have been demonstrated to be selective HDAC 1, 2 and 3 inhibitors with efficacy in xenograft models, trifluoromethyl ketones have been shown to be selective inhibitors for class II HDACs and recently have been revealed to bind in the active site of the enzyme in their hydrated form.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据