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Zebrafish small molecule screens: Taking the phenotypic plunge.

Target based chemical screens are a mainstay of modern drug discovery, but the effectiveness of this reductionist approach is being questioned in light of declines in pharmaceutical R & D efficiency. In recent years, phenotypic screens have gained increasing acceptance as a complementary/alternative approach to early drug discovery. We discuss the various model organisms used in phenotypic screens, with particular focus on zebrafish, which has emerged as a leading model of in vivo phenotypic screens. Additionally, we anticipate therapeutic opportunities, particularly in orphan disease space, in the context of rapid advances in human Mendelian genetics, electronic health record (EHR)-enabled genome-phenome associations, and genome editing.

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