Flexible assays to determine target engagement and selectivity of DUB inhibitors in cell lysates, cell cultures, or tissue samples
DUBprofiler-Cell™ and DUBprofiler-Tissue™ use activity-based probes (ABP) to engage and capture active DUBs (the ‘DUBome’) in cell lysates, cell cultures or tissue samples.
By revealing which DUBs are engaged and captured by the ABP in a given cell or tissue, target engagement of test compounds with any one or all of these DUBs can then be determined, to establish compound selectivity. Biomarkers associated with the mechanism of action can also be measured in the same samples.
Evaluating DUB target engagement in the context of a live cell or tissue environment can support programmes as they move towards clinical development, for example, the ability to demonstrate DUB target engagement in tissues derived from compound-dosed animals, which can be correlated with pharmacokinetic data.
DUBprofiler-Cell and DUBprofiler-Tissue can also be used to identify and validate DUB targets by revealing which DUBs may be more prevalent and active in a given disease setting.