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Chemical libraries

How dark is HTS dark matter?

Selecting compounds for the chemical library is the foundation of high-throughput screening (HTS). After some years and multiple HTS campaigns, many molecules in the Novartis and NIH Molecular Libraries Program screening collections have never been found to be active. An in-depth exploration of the bioactivity of this 'dark matter' does in fact reveal some compounds of interest.

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Figure 1: A brief tale of the origin and fate of HTS libraries.

Marina Coral Spence/Nature Publishing Group


  1. Wassermann, A.M. et al. Nat. Chem. Biol. doi:10.1038/nchembio.1936 (19 October 2015).

    Article  CAS  Google Scholar 

  2. Polishchuk, P.G. et al. J. Comput. Aided Mol. Des. 27, 675–679 (2013).

    Article  CAS  Google Scholar 

  3. Huggins, D.J. et al. ACS Chem. Biol. 6, 208–217 (2011).

    Article  CAS  Google Scholar 

  4. Baell, J.B. & Holloway, G.A. J. Med. Chem. 53, 2719–2740 (2010).

    Article  CAS  Google Scholar 

  5. Leeson, P.D. & Springthorpe, B. Nat. Rev. Drug Discov. 6, 881–890 (2007).

    Article  CAS  Google Scholar 

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Correspondence to Ricardo Macarron.

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Macarron, R. How dark is HTS dark matter?. Nat Chem Biol 11, 904–905 (2015).

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