P31-10 Protein Turnover Atlas: A Comprehensive Resource for Drug Development

Efficacy, pharmacodynamics and safety of drug modalities such as targeted protein degraders and covalent inhibitors are critically influenced by the cellular half-life of their target (and off-target) protein(s). Accurate and comprehensive data on endogenous protein turnover can inform risk assessment, guide modality selection and play a critical role for PK/PD modeling. Here, we employed an optimized pulsed SILAC (Stable Isotope Labelling with Amino acids in Cell culture) approach to systematically determine the half-lives of ~15.000 proteins across more than 40 cell models representing diverse tissue and disease contexts. The resulting data exhibit high consistency among protein complex subunits and correlate strongly with previously published datasets from well-characterized systems like HeLa cells. Remarkably, even rapid protein degradation events are captured robustly, highlighting the reliability and precision of the dataset. The Protein Turnover Atlas serves as a valuable resource for the safety evaluation and development of protein turnover – dependent drug modalities, providing unique insights across a wide range of cell types and biological contexts.