NAD+激酶
胞浆
氧化应激
生物
药物发现
细胞代谢
细胞生物学
新陈代谢
生物化学
氧化磷酸化
计算生物学
体内
酶
遗传学
作者
Yuzheng Zhao,Qingmin Hu,Feixiong Cheng,Ni Su,Aoxue Wang,Yejun Zou,Hanyang Hu,Xianjun Chen,Hai‐Meng Zhou,Xinzhi Huang,Kai Yang,Qian Zhu,Xue Wang,Jing Yi,Linyong Zhu,Xuhong Qian,Lixin Chen,Yun Tang,Joseph Loscalzo,Yi Yang
标识
DOI:10.1016/j.cmet.2015.04.009
摘要
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.
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