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

被引：28

作者：

Estoppey, David ^{[1
]}

Hewett, Jeffrey W. ^{[2
]}

Guy, Chantale T. ^{[2
]}

Harrington, Edmund ^{[2
]}

Thomas, Jason R. ^{[2
]}

Schirle, Markus ^{[2
]}

Cuttat, Rachel ^{[1
]}

Waldt, Annick ^{[1
]}

Gerrits, Bertran ^{[1
,3
]}

Yang, Zinger ^{[2
]}

Schuierer, Sven ^{[1
]}

Pan, Xuewen ^{[2
]}

Xie, Kevin ^{[2
]}

Carbone, Walter ^{[1
]}

Knehr, Judith ^{[1
]}

Lindeman, Alicia ^{[2
]}

Russ, Carsten ^{[2
]}

Frias, Elizabeth ^{[2
]}

Hoffman, Gregory R. ^{[2
]}

Varadarajan, Malini ^{[2
]}

Ramadan, Nadire ^{[2
]}

Reece-Hoyes, John S. ^{[2
]}

Wang, Qiong ^{[2
]}

Chen, Xin ^{[2
]}

McAllister, Gregory ^{[2
]}

Roma, Guglielmo ^{[1
]}

Bouwmeester, Tewis ^{[1
]}

Hoepfner, Dominic ^{[1
]}

机构：

[1] Novartis Pharma AG, Novartis Inst BioMed Res, Forum 1 Novartis Campus, CH-4056 Basel, Switzerland

[2] Novartis Inst BioMed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA

[3] ETH, Dept Chem & Appl Biosci, Vladimir Prelogweg 3, CH-8093 Zurich, Switzerland

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

SCREENS; MYC; TARGET;

D O I：

10.1038/srep42728

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 phosphoribosyltrans ferase (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.

引用

页数：6

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