期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 9, 期 1, 页码 127-135出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c0ob00592d
关键词
-
资金
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Cancer Research UK
- Cancer Research UK [6947] Funding Source: researchfish
Based on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2 histone Ne-methyl lysyl demethylase family, 3-substituted pyridine 2,4-dicarboxylic acids were identified as potential inhibitors with possible selectivity over other human 2OG oxygenases. Microwave-assisted palladium-catalysed cross coupling methodology was developed to install a diverse set of substituents on the sterically demanding C-3 position of a pyridine 2,4-dicarboxylate scaffold. The subsequently prepared di-acids were tested for in vitro inhibition of the histone demethylase JMJD2E and another human 2OG oxygenase, prolyl-hydroxylase domain isoform 2 (PHD2, EGLN1). A subset of substitution patterns yielded inhibitors with selectivity for JMJD2E over PHD2, demonstrating that structure-based inhibitor design can enable selective inhibition of histone demethylases over related human 2OG oxygenases.
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