In-cell NMR: From target structure and dynamics to drug screening

The cellular environment can affect the structure and function of pharmacological targets and the interaction with potential drugs. Such complexity is often overlooked in the first steps of drug design, where compounds are screened and optimized in vitro, leading to high failure rates in the pre-clinical and clinical tests. In-cell NMR spectroscopy has the potential to fill this gap, as it allows structural studies of proteins and nucleic acids directly in living cells, from bacteria to human-derived, providing a unique way to investigate the structure and dy-namics of ligand???target interactions in the native cellular context. When applied to drug screening, in-cell NMR provides insights on binding kinetics and affinity toward a cellular target, offering a powerful tool for improving drug potency at an early stage of drug development.

Automated summary

The cellular environment plays a crucial role in the structure and function of drug targets and their interaction with potential drugs. In-cell NMR spectroscopy allows for direct studies of protein and nucleic acid structures in living cells, providing a unique approach to investigating ligand-target interactions in their native cellular context. When applied to drug screening, in-cell NMR can provide insights into binding kinetics and affinity towards cellular targets, offering a powerful tool for improving drug potency at an early stage of development.