The Zebrafish: A Powerful Platform forIn Vivo, HTS Drug Discovery

Abstract

The zebrafish (Danio rerio) is an emerging vertebrate model for drug discovery that permits whole animal drug screens with excellent throughput, combined with ease of use and low cost. This review will begin with a discussion on the background, suitability, and advantages of this vertebrate model system and then, citing specific examples, will describe the utility of zebrafish at specific stages in the drug development pipeline. We will end with a synopsis of recent drug screens based on morphological disruptions, genetic disease models, fluorescent markers, behavioral changes, and specific targets. The numerous advantages of this whole animal approach provide new promise for the discovery of safe, specific, and powerful new drugs.

From cutting edge to guideline: A first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system

“…Nevertheless, it appears that most teratogenic compounds can elicit teratogenic effects at very early life stages, as somite formation and heart development seem to be by far the most sensitive structures in the developing ZF to teratogenic compounds [35]. In the ZF, organogenesis of the main organs is completed by 72 hpf, most organs are fully developed by 96 hpf, and by 120 hpf the development of the larva is completed [18,36].…”

Toxins and Drug Discovery

“…However, it may be possible to screen for novel activities using model organisms (such as nematodes (Caenorhabditis elegans) and zebrafish (Danio rerio) that have found some use in other drug discovery projects (Giacomotto and S egalat, 2010;Delvecchio et al, 2011;Asnani and Peterson, 2014;Bruni et al, 2014). Various zebrafish lines are available to allow effects on specific developmental and physiological process to be readily studied in transparent embryos in 96-well plates, and model systems for a wide range of human tumours are being developed in zebrafish (Mimeault and Batra, 2013).…”

Modeling Human Disease and Development in Zebrafish

“…The efficacy and toxicity of new compounds can be simultaneously assessed by employing this method [43]. The applicability and advantages of using zebrafish embryos over other models in drug screening have reviewed in detail [44][45][46]. Large scale chemical screening using zebrafish have been conducted recently with the aim of identifying novel biological and therapeutic compounds [47].…”