Synthesis, Activity and Metabolic Stability of Non-Ribose Containing Inhibitors of Histone Methyltransferase DOT1L.
Synthesis, Activity and Metabolic Stability of Non-Ribose Containing Inhibitors of Histone Methyltransferase DOT1L.
复制标题
DOI：
10.1039/c3md00021d
复制
发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Deng L;Zhang L;Yao Y;Wang C;Redell MS;Dong S;Song Y
组蛋白甲基转移酶DOT1L是MLL白血病的药物靶标。我们报告了含环烷的化合物的有效合成，可有效，有选择地抑制DOT1L（Ki = 1.1 nm）以及H3K79甲基化（IC50〜200 nm）。重要的是，该化合物在血浆和肝微粒体中表现出很高的稳定性，这表明它是一种更好的候选药物。
Histone methyltransferase DOT1L is a drug target for MLL leukemia. We report an efficient synthesis of a cyclopentane-containing compound that potently and selectively inhibits DOT1L (Ki = 1.1 nM) as well as H3K79 methylation (IC50 ~ 200 nM). Importantly, this compound exhibits a high stability in plasma and liver microsomes, suggesting it is a better drug candidate.