期刊
CHEMISTRY & BIOLOGY
卷 22, 期 2, 页码 273-284出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2014.12.015
关键词
-
资金
- Bankhead-Coley Cancer Research Program, Florida Department of Health [09BB-11, 09BW-05, 4BF02]
- NIH Roadmap Initiative [U54MH084512]
- China Scholarship Council
Inhibitors of histone deacetylases (HDACi) hold considerable therapeutic promise as clinical anticancer therapies. However, currently known HDACi exhibit limited isoform specificity, off-target activity, and undesirable pharmaceutical properties. Thus, HDACi with new chemotypes are needed to overcome these limitations. Here, we identify a class of HDACi with a previously undescribed benzoylhydrazide scaffold that is selective for the class I HDACs. These compounds are competitive inhibitors with a fast-on/slow-off HDAC-binding mechanism. We show that the lead compound, UF010, inhibits cancer cell proliferation via class I HDAC inhibition. This causes global changes in protein acetylation and gene expression, resulting in activation of tumor suppressor pathways and concurrent inhibition of several oncogenic pathways. The isotype selectivity coupled with interesting biological activities in suppressing tumor cell proliferation support further preclinical development of the UF010 class of compounds for potential therapeutic applications.
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