Fragment-Based Drug Discovery

Fragment-based drug discovery (FBDD) is a new paradigm in drug discovery that utilizes very small molecules - fragments of larger molecules. It is a faster, cheaper, smarter way to do drug discovery, as shown by the number of pharmaceutical companies that have embraced this approach and the biotechnology companies who use fragments as their sole source of drug discovery. Fragment-Based Drug Discovery: A Practical Approach is a guide to the techniques and practice of using fragments in drug screening. The emphasis is on practical guidance, with procedures, case studies, practical tips, and contributions from industry. Topics covered include: an introduction to fragment based drug discovery, why using fragments is a more efficient process than predominant models, and what it means to have a successful FBDD effort. setting up an FBDD project library building and production NMR in fragment screening and follow up application of protein-ligand NOE matching to the rapid evaluation of fragment binding poses target immobilized NMR screening: validation and extension to membrane proteins in situ fragment-based medicinal chemistry: screening by mass spectrometry computational approaches to fragment and substructure discovery and evaluation virtual fragment scanning: current trends, applications and web based tools fragment-based lead discovery using covalent capture methods case study from industry: the identification of high affinity beta-secretase inhibitors using fragment-based lead generation With contributions from industry experts who have successfully set up an industrial fragment-based research program, Fragment-Based Drug Discovery: A Practical Approach offers essential advice to anyone embarking on drug discovery using fragments and those looking for a new approach to screening for drugs.

Fragment-based drug discovery (FBDD) is a new paradigm in drugdiscovery that utilizes very small molecules - fragments of largermolecules. It is a faster, cheaper, smarter way to do drugdiscovery, as shown by the number of pharmaceutical companies thathave embraced this approach and the biotechnology companies who usefragments as their sole source of drug discovery.Fragment-Based Drug Discovery: A Practical Approach is aguide to the techniques and practice of using fragments in drugscreening. The emphasis is on practical guidance, with procedurescase studies, practical tips, and contributions from industry.Topics covered include:* an introduction to fragment based drug discovery, whyusing fragments is a more efficient process than predominantmodels, and what it means to have a successful FBDD effort.* setting up an FBDD project* library building and production* NMR in fragment screening and follow up* application of protein-ligand NOE matching to the rapidevaluation of fragment binding poses* target immobilized NMR screening: validation and extension tomembrane proteins* in situ fragment-based medicinal chemistry: screening bymass spectrometry* computational approaches to fragment and substructure discoveryand evaluation* virtual fragment scanning: current trends, applicationsand web based tools* fragment-based lead discovery using covalent capturemethods* case study from industry: the identification of high affinitybeta-secretase inhibitors using fragment-based lead generationWith contributions from industry experts who have successfullyset up an industrial fragment-based research programFragment-Based Drug Discovery: A Practical Approach offersessential advice to anyone embarking on drug discovery usingfragments and those looking for a new approach to screening fordrugs.

1. Introduction to Fragment based Drug Discovery (Tim Mitchell andMike Cherry).2. Building the Perfect Beast: Designing a Fragment Process toFit Your Needs (Edward Zartler and Michael Shapiro).3. Assembling a Fragment Library (Mark Brewer, Osamu IchiharaChristian Kirchhoff, Markus Schade, and Mark Whittaker).4. The Practical Aspects of Using NMR in Fragment BasedScreening (Johan Schultz).5. Application of Protein-Ligand NOE Matching to the RapidEvaluation of Fragment Binding Poses (William J. Metzler, Brian L.Claus, Patricia McDonnell, Stephen R. Johnson, Valentina GoldfarbMalcolm E. Davis, Luciano Mueller, and Keith L. Constantine).6. Target Immobilized NMR Screening: Validation and Extension toMembrane Proteins (Virginie Früh, Robert J. Heetebrij andGregg Siegal).7. In situ fragment-based medicinal chemistry: screening by massspectrometry (Sally-Ann Poulsen and Gary H. Kruppa).8. Computational approaches to fragment and substructurediscovery and evaluation (Eelke van der Horst and Adriaan P.IJzerman).9. In Silico Design Chapter (Bradley Feuston, M. KatharineHolloway, Georgia McGaughey and J. Chris Culberson).10. Fragment-based lead discovery using covalent capture methods(Stig K. Hansen and Daniel A. Erlanson).11. Identification of high affinity beta-secretase inhibitorsusing fragment-based lead generation.Jeffrey S. Albert and Philip D. Edwards.