The identification of lead compounds represents the starting point for the development of new drug candidates In the field of drug discovery. Therefore it is necessary to develop robust, simple and usable hit validation techniques. NMR is now integrated as a highly usable physics-based method at all stages of the drug discovery process throughout the pharmaceutical industry. In the early stages of the discovery pipeline, NMR is a powerful tool for hit identification and NMR-based fragment screening is a widely accepted complement to high-throughput screening (HTS).
During hit triage, NMR is the only biophysical technique that can simultaneously and unambiguously measure the components in a reaction/binding mixture. Given the versatility of the technique in detecting and exploiting a wide range of physical parameters, it has become an extremely valuable component of the biophysical platform, providing a perfect complement to other biophysical techniques such as TSA, ITC and SPR. In recent years, with the development of various technologies and NMR spectrometers, NMR has played an increasingly important role in hit identification and optimization processes.
Fig.1 Popular 1D NMR assays for detecting intermolecular interactions between small molecules and their macromolecular target. (Harner, 2017)