NMR in pharmaceutical discovery and development
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NMR in pharmaceutical discovery and development Raymond S. Norton1,2 · Wolfgang Jahnke3 Received: 17 August 2020 / Accepted: 23 August 2020 © Springer Nature B.V. 2020
Drug discovery and development is a complex, time-consuming and costly endeavour. Not only does it take many years and several billion dollars to discover and develop a drug, it also requires the coordinated and seamless interplay of a plethora of skills and technologies. Owing to this complexity and cost, drug discovery and development is an area of constant innovation, and new technologies emerge and have to prove themselves in a highly competitive field. Many of them decline in importance with the passage of time, and only some persist. NMR spectroscopy is one of those technologies that has persisted for many decades, and continues to play an important and sometimes essential role, especially when dealing with difficult targets. The role of NMR in target-based drug discovery is manifold. It is an important technique for fragment-based lead discovery (FBLD), in particular for screening fragment libraries against disease-relevant targets (Doak et al. 2016; Erlanson et al. 2019). Indeed, FBLD has developed into a mature lead-discovery technology, with several drugs originating from FBLD already on the market, and many more in clinical development (Erlanson 2020; Erlanson et al. 2020). NMR also plays an important role in progressing fragment hits into lead compounds, by providing binding assays as well as valuable information on the structure and dynamics of protein–ligand complexes. Not all drugs are small molecules—in fact, biotherapeutics (“biologics”) such as antibodies and other therapeutic * Raymond S. Norton [email protected] * Wolfgang Jahnke [email protected] 1
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
2
ARC Centre for Fragment‑Based Design, Monash University, Parkville, VIC 3052, Australia
3
Chemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Virchow‑16.3.249, 4002 Basel, Switzerland
proteins have overtaken small molecules in both numbers and sales (Urquhart 2020a, b). For this important class of therapeutics, the impact of NMR is more in development rather than discovery. Biologics have to be quality controlled for batch-to-batch consistency, and formulated for optimal properties and stability. From a technical point of view, the challenge in these tasks is that NMR needs to be performed on the actual drug substance, so that isotope labelling is rarely an option. The articles in this Special Issue of the Journal of Biomolecular NMR on Pharmaceutical Discovery and Development exemplify those areas where NMR is having significant impact in the drug discovery and development process, and we are grateful to all of the authors for writing excellent reviews, perspectives or case studies that reflect the role of NMR in this continually evolving field. A fundamental understanding of
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