Proteomics Meets Dose-Response: A New Paradigm for Deciphering Drug Effects.

Abstract

In a groundbreaking study, Eckert and colleagues introduce DecryptE, an innovative approach to dose-resolved proteomics that significantly advances our understanding of drug effects at the proteomic level. This method integrates cutting-edge sample preparation and mass spectrometry technologies, establishing a robust platform for high-throughput proteome analysis. DecryptE enables the quantification of over 7,000 proteins per hour and was employed to study 144 clinical drugs and research compounds, generating over 1 million dose-response curves using Jurkat acute T cell leukemia cells as a model system. The platform demonstrates outstanding reproducibility, ensuring reliable and consistent results across multiple experiments. By providing detailed information on drug potency and efficacy, DecryptE allows the identification of subtle changes in protein expression and facilitates the clustering of drugs based on their proteomic profiles. This study not only reveals novel drug mechanisms but also creates a comprehensive resource that can be utilized by the broader research community. Furthermore, it highlights the potential of integrating proteomics-and potentially other omics modalities in the future-with dose-response analysis to advance pharmacological research and improve therapeutic strategies.