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

Article Details

Citation

Berkers CR, Verdoes M, Lichtman E, Fiebiger E, Kessler BM, Anderson KC, Ploegh HL, Ovaa H, Galardy PJ

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

Nat Methods. 2005 May;2(5):357-62. Epub 2005 Apr 21.

PubMed ID
15846363 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
BortezomibProteasome subunit beta type-1ProteinHumans
Yes
Inhibitor
Details
BortezomibProteasome subunit beta type-5ProteinHumans
Yes
Inhibitor
Details