Deng Lisheng, Zhang Li, Yao Yuan, Wang Cong, Redell Michele S, Dong Shuo, Song Yongcheng
Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, United States. ; Tel: +1 713-798-7415.
Medchemcomm. 2013 May 1;4(5):822-826. doi: 10.1039/C3MD00021D.
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 (K = 1.1 nM) as well as H3K79 methylation (IC ~ 200 nM). Importantly, this compound exhibits a high stability in plasma and liver microsomes, suggesting it is a better drug candidate.
组蛋白甲基转移酶DOT1L是MLL白血病的一个药物靶点。我们报道了一种含环戊烷化合物的高效合成方法，该化合物能有效且选择性地抑制DOT1L（K = 1.1 nM）以及H3K79甲基化（IC~200 nM）。重要的是，该化合物在血浆和肝微粒体中表现出高稳定性，表明它是一个更好的药物候选物。
