Validating Targets For Targeted Protein Degradation Using dTAG – A Comprehensive Workflow Solution

Degraders and the field of Targeted Protein Degradation offer a mechanistically differentiated way to modulate target proteins using small molecules. While a small molecule inhibitor will block or modulate a specific protein domain or function (for example an enzymatic role), a Degrader will knockdown the entire protein, removing all possible functions. Inhibition therefore does not always phenocopy degradation and careful assessment of potential targets for new Degrader development programs is vital. Target validation is therefore an important stage of the Degrader development project workflow.

TAG degradation technology offers a generalizable strategy to degrade, in principle, any intracellular protein of interest (POI). Its key benefit is that it does not rely on the pre-existence of a ligand or PROTAC® for the POI. The broad applicability that it offers makes this a useful strategy for exploration and validation of targets, particularly in the context of new Degrader development programs.

In this paper we present data to highlight a full dTAG workflow solution, from custom KI cell lines for a protein of interest, to different dTAG Degraders available for treatment and subsequent quantitative characterization using an automated high throughput western blotting platform, Simple Western.