Journal
CHEMISTRY & BIOLOGY
Volume 10, Issue 9, Pages 881-892Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2003.08.009
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Funding
- NCI NIH HHS [R01 CA097061-01, R01 CA097061-02, 1R01 CA97061-01] Funding Source: Medline
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We present a method for testing many biological mechanisms in cellular assays using an annotated library of 2036 small organic molecules. This annotated compound library represents a large-scale collection of compounds with diverse, experimentally confirmed biological mechanisms and effects. We found that this chemical library is (1) more structurally diverse than conventional, commercially available libraries, (2) enriched in active compounds in a tumor cell viability assay, and (3) capable of generating hypotheses regarding biological mechanisms underlying cellular processes. We elucidated biological mechanisms relevant to the antiproliferative activity of 85 compounds from this library that were selected using a high-throughput cell viability screen. We developed a novel automated scoring system for identifying statistically enriched mechanisms among such a subset of compounds. This scoring system can identify both previously known and potentially novel antiproliferative mechanisms.
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