ArticleCell metabolism2015
SoNar, a Highly Responsive NAD+/NADH Sensor, Allows High-Throughput Metabolic Screening of Anti-tumor Agents.
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Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers.
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222citing papers in PubMed
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222 citing papers in PubMed, 414 citations in OpenAlex.
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162 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Yuzheng ZhaoSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Collaborative Innovation Center of Genetics and Development, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Qingxun HuSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Feixiong ChengShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Ni SuSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Aoxue WangSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Yejun ZouSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Hanyang HuSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Xianjun ChenSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Hai-Meng ZhouZhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China.
Xinzhi HuangDepartment of Biochemistry and Molecular Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai 200025, China.
Kai YangDepartment of Biochemistry and Molecular Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai 200025, China.
Qian ZhuSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Xue WangSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Jing YiDepartment of Biochemistry and Molecular Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai 200025, China.
Linyong ZhuKey Laboratory for Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Xuhong QianShanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Lixin ChenShanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai 201615, China.
Yun TangShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
Joseph LoscalzoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yi YangSynthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Optogenetics & Molecular Imaging Interdisciplinary Research Center, CAS Center for Excellence in Brain Science, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Collaborative Innovation Center of Genetics and Development, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. Electronic address: yiyang@ecust.edu.cn.
East China University of Science and Technology · CNShanghai Jiao Tong University · CNBrigham and Women's Hospital · USTsinghua University · CN
Funding
Tissue AnalysesP01HL048743 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 1992 to 2014
$26.3MGPx-3 and Peroxide Flux in the Endothelial CellR37HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2007 to 2016
$4.3MThe Phathophenotype Landscape of Complex DiseaseU01HL108630 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2011 to 2014
$2.7MPLATELET DERIVED REACTIVE OXYGEN SPECIES AND PLAQUER01HL061795 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 1998 to 2006
$1.6MNHLBI NIH HHS HL048743NHLBI NIH HHS HL061795NHLBI NIH HHS HL108630NHLBI NIH HHS P01 HL048743NHLBI NIH HHS R01 HL061795NHLBI NIH HHS R37 HL061795NHLBI NIH HHS U01 HL108630
Abstract
The altered metabolism of tumor cells confers a selective advantage for survival and proliferation, and studies have shown that targeting such metabolic shifts may be a useful therapeutic strategy. We developed an intensely fluorescent, rapidly responsive, pH-resistant, genetically encoded sensor of wide dynamic range, denoted SoNar, for tracking cytosolic NAD(+) and NADH redox states in living cells and in vivo. SoNar responds to subtle perturbations of various pathways of energy metabolism in real time, and allowed high-throughput screening for new agents targeting tumor metabolism. Among > 5,500 unique compounds, we identified KP372-1 as a potent NQO1-mediated redox cycling agent that produced extreme oxidative stress, selectively induced cancer cell apoptosis, and effectively decreased tumor growth in vivo. This study demonstrates that genetically encoded sensor-based metabolic screening could serve as a valuable approach for drug discovery.
Indexed as
AnimalsAntineoplastic AgentsApoptosisCell Line, TumorDrug Screening Assays, AntitumorHeterocyclic Compounds, 4 or More RingsHumansMice, NudeNADNAD(P)H Dehydrogenase (Quinone)NeoplasmsOxidation-ReductionOxidative StressPentose Phosphate PathwayTetrazolesAntineoplastic AgentsHeterocyclic Compounds, 4 or More RingsKP372-1NADNAD(P)H Dehydrogenase (Quinone)NQO1 protein, humanTetrazoles
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