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Target profiling of small molecules by chemical proteomics

Nature Chemical Biology volume 5, pages 616–624 (2009)Cite this article

Abstract

The medical and pharmaceutical communities are facing a dire need for new druggable targets, while, paradoxically, the targets of some drugs that are in clinical use or development remain elusive. Many compounds have been found to be more promiscuous than originally anticipated, which can potentially lead to side effects, but which may also open up additional medical uses. As we move toward systems biology and personalized medicine, comprehensively determining small molecule–target interaction profiles and mapping these on signaling and metabolic pathways will become increasingly necessary. Chemical proteomics is a powerful mass spectrometry–based affinity chromatography approach for identifying proteome-wide small molecule–protein interactions. Here we will provide a critical overview of the basic concepts and recent advances in chemical proteomics and review recent applications, with a particular emphasis on kinase inhibitors and natural products.

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Figure 1
Figure 2
Figure 3: Stable isotope labeling–based quantitative mass spectrometry approaches in chemical proteomics.
Figure 4: Complementarity of various omics technologies providing a systems-level understanding of small-molecule perturbation of biological pathways and drug effects.

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Acknowledgements

We thank M. Brehme for graphical assistance and our colleagues for providing information about the most current publications in press. We acknowledge financial support from the Austrian Federal Ministry for Science and Research under the GEN-AU program (GZ 200.142/1-VI/1/2006).

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    Uwe Rix & Giulio Superti-Furga

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G.S.-F. holds stocks of Cellzome AG.

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Rix, U., Superti-Furga, G. Target profiling of small molecules by chemical proteomics. Nat Chem Biol 5, 616–624 (2009). https://doi.org/10.1038/nchembio.216

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