Target profiling of small molecules by chemical proteomics

Nat Chem Biol. 2009 Sep;5(9):616-24. doi: 10.1038/nchembio.216.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Drug Design*
  • Ligands
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Proteomics / methods*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*


  • Biological Products
  • Ligands
  • Protein Kinase Inhibitors
  • Small Molecule Libraries