ArticlebioRxiv : the preprint server for biology2025
Cellular Selectivity Analyses Reveal Distinguishing Profiles for Type II Kinase Inhibitors.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
A pivotal part of kinase chemical probe and drug development is assessment of the selectivity of a putative lead compound. While there is no consensus around the size of an appropriate panel or the type of assay(s) that are most appropriate, there is concurrence that gauging the number of on- and off-targets of a kinase inhibitor is essential. Historically, kinase selectivity panels have been comprised of cell-free assays. As pharmacology takes place in cells, we have compared profiling results generated using the cell-free assays to those obtained when a panel of cellular target engagement NanoBRET assays is used to assess selectivity in intact cells. Comparison of the data sets demonstrates divergent results that can influence chemical probe prioritization. Furthermore, we identify unanticipated kinase interactions in cells for type II kinase inhibitors that are not observed in biochemical, cell-free systems.
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