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2016/03/18

Zebrafish-Based Drug Discovery and Systems Pharmacology

Zebrafish-Based Drug Discovery and Systems Pharmacology

Toshio Tanaka, Yuhei Nishimura, Yasuhito Shimada, Reiko Kawase, Junko Koiwa, Shota Sasagawa, Koki Kawaguchi, Michiko Ariyoshi, Hiroko Nakayama, Yuka Hayakawa,Yuka Takahashi, Chizuru Hirota, Soichiro Murakami, Yoshifumi Ashikawa, Mizuki Yuge

Department of Pharmacogenomics and Systems Pharmacology, Mie University Graduate School of Medicine, Mie University Medical Zebrafish Research Center, Tsu 514-8507, Japan

The zebrafish has become an important and prominent vertebrate model for human diseases and has already contributed to several examples of successful Phenotype-based drug discovery. Because its conservation with human in disease-associated targets1), pathology2), pathophysiology3), pharmacokinetics, pharmacodynamics, the existence of many genomic tools and the ease with which phenotype-based screening can be performed. Moreover, its small size, large numbers and optical clarity make it advantageous for high-throughput in vivo quantitative live imaging screen4) 5) 6). For the zebrafish to become useful in drug development more broadly, key hurdles must be overcome, including a more comprehensive elucidation of the similarities and differences between human and zebrafish biology. Recent studies have begun to establish the capabilities and limitations of zebrafish for disease modelling, drug screening, target identification7), pharmacology8) 9) ,and toxicology10). Here, we propose the strategy of zebrafish-based quantitative and systems pharmacology, which synergistically combine the desirable features of systems pharmacology and emerging technology of zebrafish-based screening system for functional omics and chemical biology. Zebrafish-based systems pharmacology that analyze in vivo regulatory networks involved in drug action can account for a drug’s multiple targets and the effects of genomic, epigenomic, and posttranslational changes on the drug efficacy. This next generation systems pharmacology can drive drug discovery11) and shape personalized medicine12) and is hoped that the zebrafish will have a key role in accelerating the emergence of clinical personalized medicine in oncology13).

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