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- Title
Identification of a novel NAMPT inhibitor by CRISPR/Cas9 chemogenomic profiling in mammalian cells.
- Authors
Estoppey, David; Hewett, Jeffrey W.; Guy, Chantale T.; Harrington, Edmund; Thomas, Jason R.; Schirle, Markus; Cuttat, Rachel; Waldt, Annick; Gerrits, Bertran; Yang, Zinger; Schuierer, Sven; Pan, Xuewen; Xie, Kevin; Carbone, Walter; Knehr, Judith; Lindeman, Alicia; Russ, Carsten; Frias, Elizabeth; Hoffman, Gregory R.; Varadarajan, Malini
- Abstract
Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets and the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments of this nature have been limited to fungal systems due to lack of mammalian genome-wide deletion collections. With the example of a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that the CRISPR/Cas9 system enables the generation of transient homo- and heterozygous deletion libraries and allows for the identification of efficacy targets and pathways mediating hypersensitivity and resistance relevant to the compound mechanism of action.
- Publication
Scientific Reports, 2017, p42728
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep42728