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Know your target, know your molecule

The pharmaceutical industry continues to experience significant attrition of drug candidates during phase 2 proof-of-concept clinical studies. We describe some questions about the characteristics of protein targets and small-molecule drugs that may be important to consider in drug-discovery projects and could improve prospects for future clinical success.

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Figure 1: Graphical representation of mRNA expression levels of PDE4B isoforms in human tissues.
Figure 2: Emergence of ABPP technology.

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Acknowledgements

We thank many colleagues at Pfizer for their input on this topic, including T. Rolph and members of the 'chemical biology network group'. We also thank S. Hualin Xi for the graph shown in Figure 1, R. Stanton for his help in establishing the Wikipedia entry, and P. Workman (Institute of Cancer Research, UK) and A. Edwards (University of Toronto) for their helpful feedback.

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Correspondence to Mark E Bunnage.

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Bunnage, M., Gilbert, A., Jones, L. et al. Know your target, know your molecule. Nat Chem Biol 11, 368–372 (2015). https://doi.org/10.1038/nchembio.1813

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