Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a
Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a
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DOI：
10.1021/ml400496h
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发表时间：
2014-02-01
影响因子：
4.2
通讯作者：
Pappano, William N.
中科院分区：
文献类型：
--
作者：
Sweis, Ramzi F.;Pliushchev, Marina;Pappano, William N.
G9 a是一种组蛋白赖氨酸甲基转移酶，负责组蛋白H3赖氨酸9的甲基化。A-366的发现源于独特的多样性筛选命中，其通过并入丙基吡咯烷亚基以占据酶赖氨酸通道而优化。A-366是G9 a的强效抑制剂（IC 50：3.3 nM），选择性超过21种其他甲基转移酶的1000倍。
G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.