Enabling Protein Degradation Drug Discovery

PROTEOMEprofiler

A new service that reports on changes in the cellular proteome in response to any stimuli or compound treatment and provides relative quantification across the range of conditions tested.  Applications include but are not limited to:

Support of PROTAC/molecular glue drug discovery

Understanding the down – and potentially up – regulation of the entire cellular proteome is an essential element of any targeted protein degradation drug discovery programme workflow.  In this context, PROTEOMEprofiler™ can:

  • Report the relative efficacy (EC50s), selectivity, concentration and time dependencies of PROTACs, molecular glues and similar agents to support programme SAR and lead series decisions or as independent due diligence on in-licensing opportunities
  • Provide target identification and validation to support targeted protein degradation drug discovery; including determining the predicted consequence of PROTAC/molecular glue-induced target protein downregulation in a disease relevant cell line, e.g. using siRNA or CRISPR-type approaches
  • The workflow is highly flexible and provides for your cell line of choice to be examined.

Determination of compound mechanism of action

Treatment of disease-relevant cells with candidate compounds within our PROTEOMEprofiler service provides invaluable information about the mechanism of action of candidate compounds.  Analysis is entirely unbiased and proteome-wide.  Time-course and dose response studies can be efficiently incorporated into a study, alongside inactive analogues or tool compounds.  Use PROTEOMEprofiler to confirm the primary target in cells, reveal full pathway and proteomic alterations and identify potential biomarkers to assist and accelerate clinical development.

Target identification and validation

Disease-related functional changes in protein expression and associated pathways can be revealed by the PROTEOMEprofiler™ service.  Since the entire proteome of the cell or tissue is examined, this is an entirely unbiased method for identifying targets of interest including – but not limited to – the ubiquitin pathway.  Follow-up experiments utilising isogenic lines, in which candidate DUBs (or ligases) are genetically deleted, could offer further confirmation of the relevance of these targets (and associated pathway modulation) to disease, providing robust target validation.

To learn more about PROTEOMEprofiler™ and to discuss your specific requirements, email us at services@ubiquigent.com or contact us here.