Fragment-based drug design

The editors have chosen topics from both important therapeutic areas and from work that advances the discipline of medicinal chemistry. For example, cancer, metabolic syndrome and Alzheimer s disease are fields in which academia and industry are heavily invested to discover new drugs because of their considerable unmet medical need. The editors have therefore prioritized covering new developments in medicinal chemistry in these fields. In addition, important advances in the discipline, such as fragment-based drug design and other aspects of new lead-seeking approaches, are also planned for early volumes in this series. Each volume thus offers a unique opportunity to capture the most up-to-date perspective in an area of medicinal chemistry. 

Hajduk, P. J., Greer, J. (2007) A decade of fragment-based drug design strategic advances and lessons learned. Nat Rev Drug Discov 6, 211-219. 

Key words Fragment-based drug design, fragment screening, ligand efficiency, NMR, X-ray... 

In this overview of fragment-based drug design, we will expand on the application of NMR and X-ray crystallography as the tools for biophysical screening. Common protocols will be presented, as well as the strengths and limitations of each approach. 

Mitchell, T., and Cherry, M. (2005). Fragment-based drug design. Innov. Pharm. Technol. 16, 34-36. 

Bartoli, S., Fincham, C. I., and Fattori, D. (2007). Fragment-based drug design combining philosophy with technology. Current Opinion in Drug Discovery and Development 10, 422-429. 

R.E. Hubbard, presented at the Fragment-Based Drug Design Workshop, San Diego, CA, 13 May 2007. 

Durrant JD, Friedman AJ, McCammon JA (2011) CrystalDock a novel approach to fragment-based drug design. J Chem Inf Model 51 2573-2580. doi 10.1021/ci200357y... 

SAR-by-NMR represents a very intuitive way of rational, fragment-based drug design. Two or more independently optimized ligands of different binding sites are combined to give a high-affmity binder. The example presented here deals with the development of a selective inhibitor for the protein tyrosine phosphatase IB (PTPlB).6i... 

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