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Navigating chemical space for biology and medicine

Abstract

Despite over a century of applying organic synthesis to the search for drugs, we are still far from even a cursory examination of the vast number of possible small molecules that could be created. Indeed, a thorough examination of all ‘chemical space’ is practically impossible. Given this, what are the best strategies for identifying small molecules that modulate biological targets? And how might such strategies differ, depending on whether the primary goal is to understand biological systems or to develop potential drugs?

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Figure 1: A comparison of approaches to discovering small-molecule tools or drugs.
Figure 2: Fragment-based lead screening.

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Acknowledgements

We thank R. W. Spencer, J. Everett and J. Mason for discussions and advice during the preparation of this manuscript.

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A. Hopkins is employed by the Pfizer Global Research and Development.

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Lipinski, C., Hopkins, A. Navigating chemical space for biology and medicine. Nature 432, 855–861 (2004). https://doi.org/10.1038/nature03193

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