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Nat Chem Biol. 2014 Aug;10(8):626-8. doi: 10.1038/nchembio.1551. Epub 2014 Jun 15.

DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.

Author information

1
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York, USA.
2
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA.

Abstract

To identify physiological targets of drugs and bioactive small molecules, we developed an approach, named DrugTargetSeqR, which combines high-throughput sequencing, computational mutation discovery and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-based genome editing. We applied this approach to ispinesib and YM155, drugs that have undergone clinical trials as anticancer agents, and uncovered mechanisms of action and identified genetic and epigenetic mechanisms likely to cause drug resistance in human cancer cells.

PMID:
24929528
PMCID:
PMC4123312
DOI:
10.1038/nchembio.1551
[Indexed for MEDLINE]
Free PMC Article
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