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Updated: Jan 5, 2026
Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae
Published on: March 7, 2025
Use of Zebrafish in Drug Discovery Toxicology
Steven Cassar1, Isaac Adatto2, Jennifer L Freeman3
1Preclinical Safety , AbbVie , North Chicago , Illinois 60064 , United States.
Abstract:
Unpredicted human safety events in clinical trials for new drugs are costly in terms of human health and money. The drug discovery industry attempts to minimize those events with diligent preclinical safety testing. Current standard practices are good at preventing toxic compounds from being tested in the clinic; however, false negative preclinical toxicity results are still a reality. Continual improvement must be pursued in the preclinical realm. Higher-quality therapies can be brought forward with more information about potential toxicities and associated mechanisms. The zebrafish model is a bridge between in vitro assays and mammalian in vivo studies. This model is powerful in its breadth of application and tractability for research. In the past two decades, our understanding of disease biology and drug toxicity has grown significantly owing to thousands of studies on this tiny vertebrate. This Review summarizes challenges and strengths of the model, discusses the 3Rs value that it can deliver, highlights translatable and untranslatable biology, and brings together reports from recent studies with zebrafish focusing on new drug discovery toxicology.
Insights
Zebrafish models offer a powerful preclinical tool to improve drug discovery toxicology, reducing costly human safety events in clinical trials. This review highlights their strengths and challenges for better drug development.
Area of Science:
- Pharmacology
- Toxicology
- Developmental Biology
Background:
- Unpredicted human safety events in clinical trials are costly.
- Current preclinical drug safety testing has limitations, including false negatives.
- Improving preclinical toxicology is crucial for advancing drug discovery.
Purpose of the Study:
- To review the strengths and challenges of using zebrafish in drug discovery toxicology.
- To discuss the application of the 3Rs (Replacement, Reduction, Refinement) in zebrafish research.
- To summarize recent studies utilizing zebrafish for new drug discovery toxicology.
Main Methods:
- Review of existing literature on zebrafish in drug discovery and toxicology.
- Analysis of zebrafish model's tractability and breadth of application.
- Synthesis of findings from recent studies focusing on zebrafish toxicology.
Main Results:
- Zebrafish serve as a valuable bridge between in vitro assays and mammalian in vivo studies.
- Thousands of studies have advanced our understanding of disease biology and drug toxicity using zebrafish.
- The model offers significant potential for improving preclinical safety assessment.
Conclusions:
- Zebrafish models provide a robust platform for enhancing drug discovery toxicology.
- Further research and application of zebrafish can lead to higher-quality, safer therapies.
- Addressing translatable and untranslatable biology is key for maximizing the model's utility.
