The zebrafish embryo as a model for assessing off-target drug effects

Dis Model Mech. 2010 Nov-Dec;3(11-12):689-92. doi: 10.1242/dmm.006312. Epub 2010 Sep 27.

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

  • Animals
  • Benzothiazoles / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism
  • Drug-Related Side Effects and Adverse Reactions*
  • Embryo, Nonmammalian / drug effects*
  • Humans
  • Models, Animal*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / metabolism
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / metabolism
  • Zebrafish / embryology*

Substances

  • Benzothiazoles
  • Cholinesterase Inhibitors
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Pyrazoles
  • Pyrimidines
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • dorsomorphin
  • Toluene
  • pifithrin