Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib

Celia R. Berkers, Martijn Verdoes, Eben Lichtman, Edda Fiebiger, Benedikt M. Kessler, Kenneth C. Anderson, Hidde L. Ploegh, Huib Ovaa, Paul J. Galardy

Research output: Contribution to journalArticlepeer-review

197 Scopus citations


Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma, many of the basic pharmacologic parameters of bortezomib and its mode of action on myeloma cells remain to be determined. We describe the synthesis and use of a cell-permeant active site-directed probe, which allows profiling of proteasomal activities in living cells. When we compared proteasome activity patterns in cultured cells and crude cell extracts with this probe, we observed substantial differences, stressing the importance for bioassays compatible with live cells to ensure accuracy of such measurements. Using this probe, we investigated the in vivo subunit specificities of bortezomib and another inhibitor, MG132.

Original languageEnglish (US)
Pages (from-to)357-362
Number of pages6
JournalNature Methods
Issue number5
StatePublished - May 2005

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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