期刊
JOURNAL OF CHEMICAL INFORMATION AND MODELING
卷 50, 期 12, 页码 2112-2118出版社
AMER CHEMICAL SOC
DOI: 10.1021/ci1003637
关键词
-
Increasing evidence that many pharmaceutically relevant compounds elicit their effects through binding to multiple targets, so-called polypharmacology, is beginning to change conventional drug discovery and design strategies. In light of this paradigm shift, we have mined publicly available compound and bioactivity data for promiscuous chemotypes. For this purpose, a hierarchy of active compounds, atomic property based scaffolds, and unique molecular topologies were generated, and activity annotations were analyzed using this framework. Starting from similar to 35 000 compounds active against human targets with at least 1 mu M potency, 33 chemotypes with distinct topology were identified that represented molecules active against at least 3 different target families. Network representations were utilized to study scaffold target family relationships and activity profiles of scaffolds corresponding to promiscuous chemotypes. A subset of promiscuous chemotypes displayed a significant enrichment in drugs over bioactive compounds. A total of 190 drugs were identified that had on average only 2 known target annotations but belonged to the 7 most promiscuous chemotypes that were active against 8-15 target families. These drugs should be attractive candidates for polypharmacological profiling.
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