A single, flexible platform to identify and validate cellular DUB targets and demonstrate test compound-cellular DUB target engagement and selectivity
DUB target ID and validation
The DUBprofiler-Cell™ platform can be employed as part of your target identification / validation approaches to reveal which DUBs are expressed – and active – in any given cell or tissue type and under any given circumstances. So whether you are interested in establishing the differential activity of your candidate DUB in disease versus healthy tissue, or within an isogenic cell line pair, or under different stimuli, or whether you wish us to identify candidate DUBs in those settings, we can tailor our approach to your needs. The flexibility of this platform allows us to focus in on specific DUBs to provide a strong foundation for your target and programme, or we can use a non-biased approach to allow us to report back on the entire active DUBome in your samples to reveal novel disease-relevant DUB targets.
Determination of DUB inhibitor in-cell target engagement
With the small molecule chemical tractability of DUBs demonstrated by a number of groups through the development of high affinity and selective inhibitors (supported by the DUBprofiler™ service) it is now becoming increasingly important to determine the in-cell DUB target engagement profile of these molecules as these drug discovery programmes progress towards the clinic. We have now developed such a service with support from key collaborators.
- Determination of the DUB target engagement profile of your compound(s) in a cell lysate or a live cell environment
- Addressing; physiological protein folding, the cellular milieu for compound target engagement (pH, redox conditions etc), sub-cellular penetration (compound) and localisation (target), post-translational modifications and the presence of subunits, co-factors and substrates
- Single point and EC50 determinations
- Determination of compound-DUB cellular target engagement in the presence and absence of stimuli
- Determination of compound cell penetration
- The capability to interrogate a cell lysate environment if your molecule is not cell penetrant
- Establish cellular selectivity of your molecule by investigating the active DUBome