The zebrafish embryo as a model for assessing off-target drug effects.
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.
Strähle
Uwe
U
Institute of Toxicology and Genetics, Campus North, Karlsruhe Institute of Technology, PO Box 3640, 76021 Karlsruhe, Germany. uwe.straehle@kit.edu
Grabher
Clemens
C
D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D006801:Humans; D023421:Models, Animal; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*
D052160:Benzothiazoles; D002800:Cholinesterase Inhibitors; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C516138:dorsomorphin; D014050:Toluene; C121565:pifithrin