NMR SHAPES Screening

The SHAPES strategy is a process that employs nuclear magnetic resonance (NMR) spectroscopy to screen small, drug-like molecules in a directed search for novel (or improved) medicinal chemistry leads. This strategy typically integrates NMR screening experiments with other enabling methods in drug discovery such as enzymatic assays, high-throughput screening (HTS), X-ray crystallography, molecular modeling, and combinatorial chemistry. There are three components of any NMR-based lead discovery strategy: (1) a carefully selected library of screening compounds, (2) a NMR screening method that is well-suited to the target of interest, and (3) effective use of the information obtained through screening to generate or optimize drug leads for that target. Each of these aspects will be discussed in this chapter to provide an overview of how NMR SHAPES screening may be used in drug discovery. For additional reading, we have recently published more detailed treatments of each of these components, i.e. NMR screening library design [1,2], experimental approaches [3-5], and examples of SHAPES applications [6,7].