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Phenotypic screening

Fishing for neuroactive compounds

Nature Chemical Biology volume 6, pages 172–173 (2010)Cite this article

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A high-throughput phenotypic screen in zebrafish embryos provides distinctive signatures by which neuroactive chemicals can be classified. These “behavioral barcodes” provide a systems approach to elucidating the mechanistic neuropharmacology of drugs and novel compounds.

Serendipity aside, finding new types of compound that modulate the complex biology of the human nervous system to elicit a desired phenotype is difficult. It is even more challenging to construct relevant in vitro assays as proxies for in vivo behavioral changes to systematize lead discovery. Even for well-constructed phenotypic screens, elucidating a compound's mode of action remains a challenge. In this issue, Kokel et al.1 quantify photomotor response in larval zebrafish by measuring motion at discrete time points in the presence of a compound. From sedatives to antidepressants to anesthetics, the chemically altered response of zebrafish to light stimulation provides a readout that reproducibly classifies the main therapeutic targets and indications of human central nervous system (CNS) drugs.

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Figure 1: The complex polypharmacology of neuroactive compounds captured in biochemical and whole-animal assays.

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Authors and Affiliations

  1. Jeremy L. Jenkins and Laszlo Urban are in the Center for Proteomic Chemistry, Lead Finding Platform, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.,

    Jeremy L Jenkins & Laszlo Urban

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  1. Jeremy L Jenkins
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  2. Laszlo Urban
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Correspondence to Jeremy L Jenkins.

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The authors declare no competing financial interests.

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Jenkins, J., Urban, L. Fishing for neuroactive compounds. Nat Chem Biol 6, 172–173 (2010). https://doi.org/10.1038/nchembio.320

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