Biochemistry at scale: Seeing both the forest and the trees

Today, therapeutic drug discovery lies at the crossroads of mechanistic biochemistry and the rapidly growing fields of multi-omics and AI. How will traditionally reductionist biochemistry adapt to the increasing complexity of biological processes? We address this question by first examining historical cases in which biochemistry uncovered new biology in pathways targeted by small-molecule drugs, leading to the development of targeted disease treatments. We discuss how biochemistry is evolving with approaches such as chemical proteomics, which maps protein-drug interactions and is increasingly important for therapy development. Ultimately, the future of drug discovery will be defined by the ability to integrate high-content measurements into the process of defining actionable biochemical mechanisms: seeing both the forest and the trees through biochemistry executed 'at scale'.