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在临床前研究中使用高内涵筛选技术研究药物性肝毒性。

Using high-content screening technology for studying drug-induced hepatotoxicity in preclinical studies.

作者信息

Donato Maria Teresa, Gómez-Lechón Maria José, Tolosa Laia

机构信息

a Unidad de Hepatología Experimental , Instituto de Investigación Sanitaria La Fe (IIS La Fe) , Valencia , Spain.

b Fondo de Investigaciones Sanitarias , CIBEREHD , Madrid , Spain.

出版信息

Expert Opin Drug Discov. 2017 Feb;12(2):201-211. doi: 10.1080/17460441.2017.1271784. Epub 2016 Dec 21.

Abstract

The need for alternatives to animal experimentation and traditional testing methods has been widely discussed in recent years. This has led scientists and regulatory authorities to investigate alternative methods for toxicity testing. High-content screening (HCS) has emerged as a powerful tool in predictive toxicology since it permits molecular, cellular and tissue-based toxicity assessments. HCS allows automated image acquisition and analysis, and provides information on multiple properties of individual cells loaded simultaneously with fluorescent dyes, which is used for drug safety evaluations. Areas covered: Herein, the authors review the principles of HCS technology and some of the most widely used HCS assays for studying drug-induced hepatotoxicity in preclinical studies in general and in the pharmaceutical industry in particular. Expert opinion: The widespread acceptation of HCS by pharmaceutical companies and academic researchers highlights the potential usefulness of this technology as a prioritization tool in drug development. The improvement of different key points such as fluorescent probes or bioinformatics tools will consolidate HCS in drug discovery.

摘要

近年来,关于动物实验和传统测试方法替代方案的需求已得到广泛讨论。这促使科学家和监管机构去研究毒性测试的替代方法。高内涵筛选(HCS)已成为预测毒理学中的一项强大工具,因为它允许基于分子、细胞和组织进行毒性评估。HCS能够实现自动化图像采集与分析,并提供有关同时加载荧光染料的单个细胞多种特性的信息,这些信息被用于药物安全性评估。涵盖领域:在此,作者回顾了HCS技术的原理以及一些在临床前研究尤其是制药行业中用于研究药物诱导肝毒性的最广泛使用的HCS检测方法。专家观点:制药公司和学术研究人员对HCS的广泛认可凸显了该技术作为药物开发中优先排序工具的潜在实用性。荧光探针或生物信息学工具等不同关键点的改进将巩固HCS在药物发现中的地位。

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