Targeted Protein Degradation (TPD) with heterobifunctional small molecule compounds (e.g., PROTAC®) is a novel approach to knockdown target proteins within cells. Degraders consist of binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, and selectively remove proteins via the ubiquitin-proteasome system (UPS). Degraders have recently emerged as an attractive mechanism to explore previously “undruggable” targets. Advances in our understanding of how heterobifunctional Degraders achieve potency and selectivity will help to design more efficient degraders.
To characterize the efficacy of Degrader molecules, researchers generally run dose response curves by way of traditional SDS-PAGE Western blotting methods. But the lengthy, manual workflow and resulting low reproducibility make it an unreliable approach for the determination of DC50 values. Instead, the ideal solution would be highly reproducible, allow for easy quantitation and have a short time to results. Simple Westerns are just that—they let you separate and analyze proteins by size (or charge) from 2 kDa to 440 kDa in just 3 hours. You’ll get quantitative results, reproducibility that’s spot on, and use less sample in the process.