Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5811-3. doi: 10.1016/j.bmcl.2012.07.091. Epub 2012 Aug 2.
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.
人类组蛋白去甲基酶家族的 KDM4（JMJD2）已与前列腺癌和乳腺癌以及 X 连锁智力迟钝等疾病相关。因此，这些酶被认为是致癌基因，它们的选择性抑制可能是治疗癌症的一种可行的治疗方法。在这里，我们描述了一个针对组蛋白去甲基酶 KDM4C（JMJD2C）筛选的杂环环系统文库，以寻找新的抑制支架。鉴定出 4-羟基吡唑作为 KDM4C 的抑制剂；该支架可用于新型治疗药物的进一步开发，以及阐明 KDM4C 在表观遗传调控中的生物学作用。
