Abstract
Mass spectrometry (MS)-based proteomics is a disruptive platform in drug discovery that offers an exhaustive view of the proteome's complexity. Focusing on bottom-up MS proteomics, this technology enables high-throughput analysis of protein expression, interactions, and modifications, far surpassing the capabilities of traditional single-protein methods. The MS proteomics toolbox is essential in both early- and late-stage development of new drugs. The techniques discussed here, such as unlabeled and labeled proteomics and chemoproteomic approaches (e.g., thermal proteome profiling and photoaffinity labeling), facilitate target binding site exploration and the identification of putative off-targets. By accelerating the identification of new druggable proteins and supporting early biomarker discovery, MS proteomics significantly accelerates the preclinical-to-clinical transition. Ongoing progress in data acquisition, new computational tools, and artificial intelligence further enhances the high-throughput properties of these approaches, marking a significant step toward personalized medicine.