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Advances in Predictive Toxicology for Discovery Safety through High Content Screening
被引:16
作者:
Persson, Mikael
[1
]
Hornberg, Jorrit J.
[1
]
机构:
[1] AstraZeneca R&D Gothenburg, Innovat Med & Early Dev, Drug Safety & Metab, Pepparedsleden 1, S-43183 Molndal, Sweden
关键词:
CELL-DERIVED CARDIOMYOCYTES;
VITRO MICRONUCLEUS ASSAY;
HIGH-THROUGHPUT MEASUREMENT;
KINETIC IMAGE CYTOMETRY;
INDUCED LIVER-INJURY;
IN-VITRO;
DRUG DISCOVERY;
NEURITE OUTGROWTH;
ZEBRAFISH EMBRYOS;
RISK-ASSESSMENT;
D O I:
10.1021/acs.chemrestox.6b00248
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.
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页码:1998 / 2007
页数:10
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