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Small molecule drug discovery is expanding beyond traditional strategies focused on identifying compounds that inhibit or block the activity of proteins that cause disease. A newer approach is to selectively target proteins for removal from the cell using degrader compounds.

Proteolysis Targeting Chimeras (PROTACs) and immunomodulatory (IMiD) molecular glues are examples of small molecule degraders that facilitate Targeted Protein Degradation (TPD), by bringing the target protein into close proximity to the cell’s own E3 ligase machinery, resulting in its ubiquitination and subsequent degradation using the cell’s ubiquitin proteasome system. These small molecule degrader compounds are enabling proteins previously considered 'undruggable' to be targeted for therapeutic intervention.

Assays that can accurately quantitate target proteins and monitor their degradation are required in order to identify and characterise these compounds. They also need to be scalable for high-throughput workflows and yield reproducible data in small molecule screening. Promega now has a portfolio of cell-based assay solutions to support the development of effective degrader compounds. Download this white paper to learn more about:

  • Options and best practices for developing cell-based assays to measure endogenous target protein abundance.
  • How to detect ternary complex formation, ubiquitination, compound permeability, E3 ligase target engagement and target protein degradation.
  • How quantitative, luminescent protein tags can be used to determine efficacy, rank order and profiles of degrader compounds.

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Download the Whitepaper