Chemical and Biological Properties of Frequent Screening Hits

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• 作者：Jianwei Che ; Frederick J. King ; Bin Zhou ; Yingyao Zhou
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2012
• 出版时间：April 23, 2012
• 年：2012
• 卷：52
• 期：4
• 页码：913-926
• 全文大小：663K
• 年卷期：v.52,no.4(April 23, 2012)
• ISSN：1549-960X

文摘

High-throughput screening (HTS) has become an important technology for the drug discovery process. It has been noted that certain compounds frequently appear as hits in many screening campaigns. By mining an HTS database covering large chemical space and diverse biological functions, we identified many novel chemical features, as well as several biological processes that were associated with a significant portion of frequent hits. However, we also noted that several marketed drugs also contained characteristics that commonly were associated with frequent hits. This observation suggested that current generally employed strategies for triaging compounds may result in the removal of compounds with desirable properties. Therefore, we developed a novel strategy that overlaid chemical scaffolds and biological processes, along with empirical hit frequency data, in order to provide a more functional frequent hit triage strategy; the risk of removing biologically relevant frequent hits was reduced compared to the typical empirical hit frequency-based filtering strategy.