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Drug discovery

Combichem all over again

Nature Chemistry volume 6, pages 851–852 (2014)Cite this article

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The generation of chemical libraries for screening is a key part of the drug discovery process. Now, two studies describe attempts to combine features of natural product biosynthesis into the creation of libraries with the aim of mimicking nature's success at the production of bioactive molecules.

Combinatorial chemistry, the preparation of large diverse libraries of new compounds from defined building blocks, is such a potentially powerful technique that it has had multiple lives. The first flush of enthusiasm for it in the early 1990s did not live up to its promises — the hit rate from screening those early libraries was unexpectedly low, for one thing, and many of the libraries were not as cleanly prepared or as cleanly delineated as had been planned. This realization was followed by a retrenchment1, with many expensive pieces of lab equipment marked for distant storage rooms, but 'combichem' has never really gone away.

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Figure 1: Contemporary approaches to combinatorial chemistry.

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Authors and Affiliations

  1. Derek Lowe is at Vertex Pharmaceuticals 50 Northern Avenue, Boston, Massachussets 02210, USA,

    Derek B. Lowe

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  1. Derek B. Lowe
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Correspondence to Derek B. Lowe.

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Lowe, D. Combichem all over again. Nature Chem 6, 851–852 (2014). https://doi.org/10.1038/nchem.2074

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