期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 27, 期 8, 页码 1497-1508出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.02.029
关键词
Indazole; Janus kinase JAK2; Inhibitor; ATP site; Activity; Selectivity; Water network
资金
- National Research, Development and Innovation Office of Hungary (OTKA) [K 116904]
Structure based optimization of B39, an indazole-based low micromolar JAK2 virtual screening hit is reported. Analysing the effect of certain modifications on the activity and selectivity of the analogues suggested that these parameters are influenced by water molecules available in the binding site. Simulation of water networks in combination with docking enabled us to identify the key waters and to optimize our primary hit into a low nanomolar JAK2 lead with promising selectivity over JAK1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据