Authors: Alexander E. Yarawsky, Judith A. Ronau, Tiffany A. Thibaudeau, Aaron C. Ehlinger, Gekleng Chhor, Suki M. Hyman, Michelle A. Estrada, Vladimir Stojkovic, Michael T. DeLion, Anil Vasudevan, Justin M. Reitsma, Scott E. Warder & Lake N. Paul. A paradigm shift: analytical ultracentrifugation as a multi-attribute platform method in targeted protein degradation. European Biophysics Journal, (2025). DOI: Click Here

About This Research

Targeted protein degradation represents a revolutionary approach in drug discovery, yet characterizing the critical ternary complexes formed between degrader molecules, target proteins, and E3 ligases remains challenging. This study demonstrates how analytical ultracentrifugation serves as a comprehensive platform for evaluating multiple attributes of degrader-induced complexes simultaneously. Using the BTK-degrader-CRBN system as a model, the research showcases AUC’s unique ability to quantify complex formation, determine stoichiometry, measure binding kinetics, and assess sample purity in solution – addressing critical knowledge gaps that other methods cannot resolve.

Why This Matters

As the authors note, “several knowledge gaps remain, such as stoichiometry and how much ternary complex is formed in solution,” questions that are fundamental to optimizing degrader therapeutics. This work establishes AUC as an essential tool for TPD drug development, providing the quantitative data necessary for advancing degrader candidates through the discovery pipeline – expertise that BioAnalysis brings to our biopharmaceutical partners developing these next-generation therapeutics.