Scientific Publications

Using high-throughput screening data to discriminate compounds with single-target effects from those with side effects.

Publication TypeJournal Article
AuthorsKlekota, J., Brauner E., Roth FP, and Schreiber SL
AbstractThe most desirable compound leads from high-throughput assays are those with novel biological activities resulting from their action on a single biological target. Valuable resources can be wasted on compound leads with significant 'side effects' on additional biological targets; therefore, technical refinements to identify compounds that primarily have effects resulting from a single target are needed. This study explores the use of multiple assays of a chemical library and a statistic based on entropy to identify lead compound classes that have patterns of assay activity resulting primarily from small molecule action on a single target. This statistic, called the coincidence score, discriminates with 88% accuracy compound classes known to act primarily on a single target from compound classes with significant side effects on nonhomologous targets. Furthermore, a significant number of the compound classes predicted to have primarily single-target effects contain known bioactive compounds. We also show that a compound's known biological target or mechanism of action can often be suggested by its pattern of activities in multiple assays.
Year of Publication2006
JournalJournal of chemical information and modeling
Volume46
Issue4
Pages1549-62
Date Published (YYYY/MM/DD)2006/05/18
ISSN Number1549-9596
DOI10.1021/ci050495h
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/16859287?dopt=Abstract