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@ARTICLE{Capener:307547,
author = {J. L. Capener and M. P. Schwalm and J. D. Vasta and A.
Michaud and K. A. Teske and W. M. Marsiglia and K. V. M.
Huber and A. C. Dar and S. Knapp$^*$ and A. D. Axtman and M.
B. Robers},
title = {{A}dvances in {BRET} probes for intracellular target
engagement studies.},
journal = {Nature chemical biology},
volume = {nn},
issn = {1552-4450},
address = {Basingstoke},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2026-00044},
pages = {nn},
year = {2026},
note = {#DKTKZFB9# / epub},
abstract = {Assessing drug-target engagement in living cells is
essential for verifying the activity of pharmacological
agents. Traditional binding assays often overlook key
factors such as permeability, intracellular distribution and
complex formation that influence target occupancy in cells.
Bioluminescence resonance energy transfer (BRET)-based
probes enable direct, quantitative assessment of
small-molecule binding to proteins in live, intact cells.
BRET provides sensitive detection of target engagement
across a wide range of target classes, including
less-tractable proteins in membrane compartments. Compared
to other existing methods, BRET offers quantification of
drug occupancy at steady state and open system regimens.
Recent innovations in this platform have expanded its
utility beyond occupancy confirmation to include
applications in polypharmacology and mechanism-of-action
studies. Here, we provide an updated perspective on BRET
target engagement assays as versatile tools for chemical
biology and early-stage drug discovery.},
subtyp = {Review Article},
cin = {FM01},
ddc = {570},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41495225},
doi = {10.1038/s41589-025-02103-y},
url = {https://inrepo02.dkfz.de/record/307547},
}