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Fragment-based approaches have become a key tool for drug discovery and can yield results where other methods have failed. The pioneers in the field present a comprehensive overview of current methods and future developments, augmented by successful case studies.

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From its origins as a niche technique more than 15 years ago, fragment-based approaches have become a major tool for drug and ligand discovery, often yielding results where other methods have failed. Written by the pioneers in the field, this book provides a comprehensive overview of current methods and applications of fragment-based discovery, as well as an outlook on where the field is headed.

The first part discusses basic considerations of when to use fragment-based methods, how to select targets, and how to build libraries in the chemical fragment space. The second part describes established, novel and emerging methods for fragment screening, including empirical as well as computational approaches. Special cases of fragment-based screening, e. g. for complex target systems and for covalent inhibitors are also discussed. The third part presents several case studies from recent and on-going drug discovery projects for a variety of target classes, from kinases and phosphatases to targeting protein-protein interaction and epigenetic targets.

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PART 1: THE CONCEPT OF FRAGMENT-BASED DRUG DISCOVERY
The role of fragment-based approaches in lead finding
Selecting the right targets for fragment-based drug discovery
Theory and energetics
Enumeration of chemical fragment space
Metrics for fragment-based drug discovery
PART 2: METHODS AND APPROACHES FOR FRAGMENT-BASED DRUG DISCOVERY
Library design and implementation
Established screening technologies: SPR, NMR, Crystallography
Differential scanning fluorimetry (DSF)
Emerging screening technologies: Microscale Thermophoresis, Mass spectrometry, Chromatographic methods
Computational aspects of fragment-based drug discovery
Making fragment-based drug discovery work in academia
Fragment screening in complex systems
Reversible covalent kinase inhibitors
Emerging chemical approaches to fragment-based drug discovery
PART 3: SUCCESSES FROM FRAGMENT-BASED DRUG DISCOVERY
BACE inhibitors
Epigenetics
Fragment-based drug discovery on PPIs
Lactate dehydrogenase A
Kinase inhibitors
Integrating fragment information in mature projects

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