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Determining target engagement in living systems

Chemical probes are critical tools for elucidating the biological functions of proteins and can lead to new medicines for treating disease. The pharmacological validation of protein function requires verification that chemical probes engage their intended targets in vivo. Here we discuss technologies, both established and emergent, for measuring target engagement in living systems and propose that determining this parameter should become standard practice for chemical probe and drug discovery programs.

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Figure 1: Approaches for measuring target engagement in cellular systems.
Figure 2: Approaches for measuring target engagement in model organisms.
Figure 3: Approaches for measuring target engagement in humans.

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Acknowledgements

We are grateful for the support of the US National Institutes of Health (CA087660, CA132630, DA033760 and DA032541) and the Skaggs Institute for Chemical Biology.

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Correspondence to Benjamin F Cravatt.

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Simon, G., Niphakis, M. & Cravatt, B. Determining target engagement in living systems. Nat Chem Biol 9, 200–205 (2013). https://doi.org/10.1038/nchembio.1211

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