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.

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

“…In contrast, the interaction between growth hormone and growth hormone receptor (1axi) is spread across a greater area, with a lower density of interactions (K d~1 0 À9 ). Except where otherwise indicated, surface and cartoon representations were prepared using PyMOL (DeLano 2002b) There is also a knowledge gap in selecting the best approaches for finding inhibitors, though a range of methods -both computational and experimentalhave been successfully used (Betzi et al 2009;Trosset et al 2006;Ciulli and Abell 2007;Fattori et al 2008;Pellecchia et al 2008;Casey et al 2009). Regardless of the primary screening method used, it is crucial to validate primary hits using orthogonal methods.…”

Extraction of multiple pure component 1H and 13C NMR spectra from two mixtures: Novel solution obtained by sparse component analysis-based blind decomposition

“…NMR spectroscopy is a powerful tool in drug discovery, especially in fragment-based drug design as an alternative to high-throughput screening [1], and in instrumental diagnostics, one of the most developing areas of current medicine [2]. It is clear that NMR spectroscopy represents a forefront of progress in post-genomic era.…”

Fluorine nuclear magnetic resonance-based assay in living mammalian cells

“…Nuclear magnetic resonance (NMR)-based approaches, which are widely used for target-based screening on purified proteins [7], show promise in this regard, but their application to compound screening in intact cells is still very limited [8,9]. Recently, 1 H NMR spectroscopy was used to screen small molecules in intact bacterial cells [10], showing that it is possible to use this technology in living cells for the identification of inhibitors against a specific target and for the evaluation of their potency.…”