Chemical and Biological Properties of Frequent Screening Hits

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.