Abstract
Although first used experimentally for the genetic analysis of vertebrate development and neurobiology, the zebrafish has been adapted as a model for many human diseases. In recent years, the zebrafish embryo has increasingly attracted the attention of chemists and pharmacologists for its utility in identifying chemicals with pharmacological activity in a whole-animal context. Its experimental virtues make it an ideal system with which to identify new bioactive molecules, and to assess their toxicity and teratogenicity at medium-to-high throughput. More recently, the zebrafish embryo has been applied to identify off-target effects of drug candidates. Here, we discuss the value of the zebrafish embryo for detecting off-target effects, and propose that this model could be useful for improving the efficiency of the drug-development pipeline.
MeSH terms
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Animals
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Benzothiazoles / pharmacology
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Cholinesterase Inhibitors / pharmacology
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Drug-Related Side Effects and Adverse Reactions*
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Embryo, Nonmammalian / drug effects*
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Humans
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Models, Animal*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Pyrazoles / pharmacology
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Pyrimidines / pharmacology
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Toluene / analogs & derivatives
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Toluene / pharmacology
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Tumor Protein p73
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / metabolism
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Zebrafish / embryology*
Substances
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Benzothiazoles
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Cholinesterase Inhibitors
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DNA-Binding Proteins
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Nuclear Proteins
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Pyrazoles
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Pyrimidines
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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dorsomorphin
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Toluene
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pifithrin