Fragment Screen

Synonyms

NMR; NMR ligand affinity screen

Definition

The development of the SAR by NMR technique in 1996 by Stephen Fesik at Abbot Laboratories resulted in a tremendous expansion in NMR ligand affinity screens throughout the pharmaceutical industry (Shuker et al. 1996). One important enhancement has been the design of the chemical library used in these NMR screens. Instead of a library of random compounds, screening libraries were constructed to contain fragments of known drugs. This was first demonstrated with the SHAPES library designed by Jonathan Moore at Vertex Pharmaceuticals (Fejzo et al. 1999). Fragment-based screens utilize a structurally diverse chemical library of low molecular-weight compounds (≤200–300 Da) that correspond to fragments of known drugs or have drug-like characteristics by adhering to Lipinski’s rule of five and exhibiting high aqueous solubility (Lipinski et al. 2001, Lipinski 2004). A fragment library is typically small (<10⁵compounds) making it amenable to...