Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2
Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2
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DOI：
10.1021/ml400494b
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发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Harmange, Jean-Christophe P.
中科院分区：
文献类型：
--
作者：
Nasveschuk, Christopher G.;Gagnon, Alexandre;Harmange, Jean-Christophe P.
描述了一系列新型小分子 Zeste 同源增强剂 2 (EZH2) 抑制剂的鉴定和开发。简洁和模块化的合成使结构活性关系得以快速发展，从而使 44 被鉴定为 EZH2 的有效 SAM 竞争性抑制剂，其剂量依赖性地降低 KARPAS-422 淋巴瘤细胞中的整体 H3K27me3。
The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.