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题名: Cardiotoxicity screening: a review of rapid-throughput in vitro approaches
作者: Li, Xichun; Zhang, Rui; Zhao, Bin; Lossin, Christoph; Cao, Zhengyu
刊名: ARCHIVES OF TOXICOLOGY
出版日期: 2016-08
卷号: 90, 期号:8, 页码:1803-1816
关键词: Cardiotoxicity ; Rapid throughput ; hERG ; Automated patch clamp ; Microelectrode array ; Fluorescence plate reader
DOI: 10.1007/s00204-015-1651-1
部门归属: 环境化学与生态毒理学国家重点实验室
英文摘要: Cardiac toxicity represents one of the leading causes of drug failure along different stages of drug development. Multiple very successful pharmaceuticals had to be pulled from the market or labeled with strict usage warnings due to adverse cardiac effects. In order to protect clinical trial participants and patients, the International Conference on Harmonization published guidelines to recommend that all new drugs to be tested preclinically for hERG (K(v)11.1) channel sensitivity before submitting for regulatory reviews. However, extensive studies have demonstrated that measurement of hERG activity has limitations due to the multiple molecular targets of drug compound through which it may mitigate or abolish a potential arrhythmia, and therefore, a model measuring multiple ion channel effects is likely to be more predictive. Several phenotypic rapid-throughput methods have been developed to predict the potential cardiac toxic compounds in the early stages of drug development using embryonic stem cells- or human induced pluripotent stem cell-derived cardiomyocytes. These rapid-throughput methods include microelectrode array-based field potential assay, impedance-based or Ca2+ dynamics-based cardiomyocytes contractility assays. This review aims to discuss advantages and limitations of these phenotypic assays for cardiac toxicity assessment.
收录类别: SCI
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内容类型: 期刊论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35814
Appears in Collections:环境化学与生态毒理学国家重点实验室_期刊论文

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Recommended Citation:
Li, Xichun,Zhang, Rui,Zhao, Bin,et al. Cardiotoxicity screening: a review of rapid-throughput in vitro approaches[J]. ARCHIVES OF TOXICOLOGY,2016,90(8):1803-1816.
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