Perspectives on NMR in drug discovery: a technique comes of age

Abstract

In the past decade, the potential of harnessing the ability of nuclear magnetic resonance (NMR) spectroscopy to monitor intermolecular interactions as a tool for drug discovery has been increasingly appreciated in academia and industry. In this Perspective, we highlight some of the major applications of NMR in drug discovery, focusing on hit and lead generation, and provide a critical analysis of its current and potential utility.

Figure 1. Overview of applications of NMR in drug discovery

NMR spectroscopy can provide critical information at early stages of hit validation and identification. NMR measurements for binding studies can represent a key step to eliminate false positives from high-throughput (HTS) campaigns, to validate putative hits from in silico screens or to identify novel scaffolds in fragment-based programmes. NMR and X-ray crystallography can also provide unique information to subsequently guide hit-to-lead optimization. ADME-tox, absorption, distribution, metabolism, excretion and toxicity.