Identifying the proteins to which small-molecule probes and drugs bind in cells Journal Article uri icon



  • ; Most small-molecule probes and drugs alter cell circuitry by interacting with 1 or more proteins. A complete understanding of the interacting proteins and their associated protein complexes, whether the compounds are discovered by cell-based phenotypic or target-based screens, is extremely rare. Such a capability is expected to be highly illuminating—providing strong clues to the mechanisms used by small-molecules to achieve their recognized actions; and; suggesting potential unrecognized actions. We describe a powerful method combining quantitative proteomics (SILAC) with affinity enrichment to provide unbiased, robust and comprehensive identification of the proteins that bind to small-molecule probes and drugs. The method is scalable and general, requiring little optimization across different compound classes, and has already had a transformative effect on our studies of small-molecule probes. Here, we describe in full detail the application of the method to identify targets of kinase inhibitors and immunophilin binders.;

publication date

  • March 24, 2009

has restriction

  • green

Date in CU Experts

  • February 28, 2014 8:34 AM

Full Author List

  • Ong S-E; Schenone M; Margolin AA; Li X; Do K; Doud MK; Mani DR; Kuai L; Wang X; Wood JL

author count

  • 17

Other Profiles

International Standard Serial Number (ISSN)

  • 0027-8424

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Additional Document Info

start page

  • 4617

end page

  • 4622


  • 106


  • 12