活性氧
药物发现
小分子
顺铂
氧化还原
过氧化物还原蛋白
药品
生物
化学
细胞生物学
癌症
癌细胞
药理学
生物化学
酶
过氧化物酶
遗传学
有机化学
化疗
作者
Yining Hao,Troy F. Langford,Sun Jin Moon,Kristen A. Eller,Hadley D. Sikes
标识
DOI:10.1016/j.chembiol.2021.09.003
摘要
Compounds that modulate H2O2 reaction networks have applications as targeted cancer therapeutics, as a subset of cancers exhibit sensitivity to this redox signal. Previous studies to identify therapeutics that induce oxidants have relied upon probes that respond to many different oxidants in cells, and thus do not report on only H2O2, a redox signal that selectively oxidizes proteins. Here we use a genetically encoded fluorescent probe for human peroxiredoxin-2 (Prx2) oxidation in screens for small-molecule compounds that modulate H2O2 pathways. We further characterize cellular responses to several compounds selected from the screen. Our results reveal that some, but not all, of the compounds enact H2O2-mediated toxicity in cells. Among them, SMER3, an antifungal, has not been reported as an oxidant-inducing drug. Several drugs, including cisplatin, that previously have been shown to induce reactive oxygen species (ROS) do not appear to oxidize Prx2, suggesting H2O2 is not among the ROS induced by those drugs.
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