Rescaling NMR for a Larger Deployment in Drug Discovery: Hyperpolarization and Benchtop NMR as Potential Game-Changers

Nuclear magnetic resonance (NMR) is recognized as the gold standard method in fragment-based drug design for screening, hit validation, and affinity determination. However, its deployment at a large scale is limited by the cost and expertise needed to implement NMR as a routine drug discovery method. The increase in the adoption of fragment-based drug design created a need for biophysics to provide high-quality data for weak ligand-target interactions that can be implemented at scale. NMR must adapt its position in drug design operations to enter this new era. The recent development of commercially available benchtop NMR spectrometers in combination with hyperpolarization methods represents an opportunity for highly deployable and scalable systems. Combining benchtop NMR with hyperpolarization methods such as d-DNP, SABRE, or photo-CIDNP enhances the sensitivity and enables the performance of fragment screening in an agile and high-throughput manner. image