Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

被引：21

作者：

Leurs, Ulrike ^{[1
]}

Clausen, Rasmus P. ^{[1
]}

Kristensen, Jesper L. ^{[1
]}

Lohse, Brian ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 18期

关键词：

KDM4C/JMJD2C; FDH assay; Small molecule inhibitors; Heterocyclic ring systems; Histone lysine demethylases; MECHANISM;

D O I：

10.1016/j.bmcl.2012.07.091

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5811 / 5813

页数：3

共 17 条

[1]

PREPARATION OF ESTERS OF 4-HYDROXYPYRAZOLE-3,5-DICARBOXYLIC ACID [J].