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  3. Identification of a novel NAMPT inhibitor by CRISPR/Cas9 chemogenomic profiling in mammalian cells

Identification of a novel NAMPT inhibitor by CRISPR/Cas9 chemogenomic profiling in mammalian cells

  • Sci Rep. 2017 Feb 16;7:42728. doi: 10.1038/srep42728.
David Estoppey 1,  Jeffrey W Hewett 2,  Chantale T Guy 2,  Edmund Harrington 2,  Jason R Thomas 2,  Markus Schirle 2,  Rachel Cuttat 1,  Annick Waldt 1,  Bertran Gerrits 1,  Zinger Yang 2,  Sven Schuierer 1,  Xuewen Pan 2,  Kevin Xie 2,  Walter Carbone 1,  Judith Knehr 1,  Alicia Lindeman 2,  Carsten Russ 2,  Elizabeth Frias 2,  Gregory R Hoffman 2,  Malini Varadarajan 2,  Nadire Ramadan 2,  John S Reece-Hoyes 2,  Qiong Wang 2,  Xin Chen 2,  Gregory McAllister 2,  Guglielmo Roma 1,  Tewis Bouwmeester 1,  Dominic Hoepfner 1
Affiliations

Affiliations

  • 1 Novartis Institutes for BioMedical Research, Novartis Pharma AG, Forum 1 Novartis Campus, CH-4056 Basel, Switzerland.
  • 2 Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
PMID: 28205648 DOI: 10.1038/srep42728
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.

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