Advances in nuclear magnetic resonance for drug discovery

Abstract

Background: Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exacerbated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project timelines. Recent advances in NMR are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/method: A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process is presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein–ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by functional annotation screening technology using NMR. Conclusion: NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques and the expansion of NMR amenable targets.