期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 10, 期 3, 页码 318-323出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.8b00546
关键词
Protein kinase C iota; fragment-based drug discovery; kinase inhibitor; C-terminal tail; hepatocellular carcinoma; nonsmall cell lung cancer
资金
- Agency for Science, Technology and Research (A*STAR) Joint Council [1231B105]
The atypical protein kinase C-iota (PKC-iota) enzyme is implicated in various cancers and has been put forward as an attractive target for developing anticancer therapy. A high concentration biochemical screen identified pyridine fragment weakly inhibiting PKC-iota with IC50 = 424 mu M. Driven by structure-activity relationships and guided by docking hypothesis, the weakly bound fragment was eventually optimized into a potent inhibitor of PKC-iota (IC50 = 270 nM). Through the course of the optimization, an intermediate compound was crystallized with the protein, and careful analysis of the X-ray crystal structure revealed a unique binding mode involving the post-kinase domain (C-terminal tail) of PKC-iota.
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