基于铑(III)的 JMJD3-H3K27me3 相互作用抑制剂和炎症反应调节剂。
Rhodium(III)-Based Inhibitor of the JMJD3-H3K27me3 Interaction and Modulator of the Inflammatory Response.
机构信息
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences , University of Macau , Macao 519020 , China.
Department of Chemistry , Hong Kong Baptist University , Kowloon Tong , Hong Kong 518000 , China.
出版信息
Inorg Chem. 2018 Nov 19;57(22):14023-14026. doi: 10.1021/acs.inorgchem.8b02256. Epub 2018 Oct 30.
We describe in this study a rhodium(III) complex 1 as a new JMJD3 inhibitor and proinflammatory mediator. Complex 1 selectively inhibited the demethylation of H3K27me3 over other similar substrates, indicating its selectivity for JMJD3 over other histone demethylases, including JMJD2D and KDM5A. In terms of mechanism, complex 1 inhibited the JMJD3-H3K27me3 interaction in mouse macrophage cells and down-regulated the expression of TNF-α. To our knowledge, complex 1 is the first metal-based inhibitor of JMJD3 activity and only the second class of JMJD3 inhibitor reported overall.
在本研究中，我们描述了一种铑（III）配合物 1，它是一种新的 JMJD3 抑制剂和促炎介质。复合物 1 选择性地抑制 H3K27me3 的去甲基化，而其他类似的底物则没有，这表明它对 JMJD3 的选择性高于其他组蛋白去甲基酶，包括 JMJD2D 和 KDM5A。就机制而言，复合物 1 抑制了 JMJD3-H3K27me3 相互作用，并下调了 TNF-α 的表达。据我们所知，复合物 1 是 JMJD3 活性的第一个基于金属的抑制剂，也是总体上报告的第二类 JMJD3 抑制剂。
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