Inhibition of Histone Demethylases by 4-Carboxy-2,2′-Bipyridyl Compounds

被引：64

作者：

Chang, Kai-Hsuan ^{[1
]}

King, Oliver N. F. ^{[1
]}

Tumber, Anthony ^{[2
]}

Woon, Esther C. Y. ^{[1
]}

Heightman, Tom D. ^{[2
]}

McDonough, Michael A. ^{[1
]}

Schofield, Christopher J. ^{[1
]}

Rose, Nathan R. ^{[1
]}

机构：

[1] Univ Oxford, Chem Res Lab, Oxford OX1 3TA, England

[2] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England

来源：

CHEMMEDCHEM | 2011年 / 6卷 / 05期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

bipyridyl derivatives; epigenetics; histone demethylases; inhibitors; 2-oxoglutarate; HYPOXIA-INDUCIBLE FACTOR; PROLYL; 4-HYDROXYLASE; SPECIFICITY; SERIES; JMJD2A;

D O I：

10.1002/cmdc.201100026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Exploiting epigenetics: 2-Oxoglutarate (2OG)-dependent histone lysine demethylases, such as JMJD2E, are potential therapeutic targets in a range of diseases. Through structure-activity relationship studies and analyses, we identified a potent 4-carboxy-2,2'-bipyridyl compound, which inhibits JMJD2E with an IC50 value of 110nM, representing a 66-fold improvement over the lead compound. These bipyridyl derivatives bind in the 2-oxoglutarate binding site. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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收藏

页码：759 / 764

页数：6

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