Erlanson D.A., Jahnke W. (Eds.) Fragment-based Drug Discovery: Lessons and Outlook

Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2016. — 527 p. — (Methods and Principles in Medicinal Chemistry. Volume 67) — ISBN: 352733775XFrom 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.The Concept of Fragment-based Drug Discovery
The Role of Fragment-based Discovery in Lead Finding
Selecting the Right Targets for Fragment-Based Drug Discovery
Enumeration of Chemical Fragment Space
Ligand Efficiency Metrics and their Use in Fragment Optimizations
Methods and Approaches for Fragment-based Drug Discovery
Strategies for Fragment Library Design
The Synthesis of Biophysical Methods In Support of Robust Fragment-Based Lead Discovery
Differential Scanning Fluorimetry as Part of a Biophysical Screening Cascade
Emerging Technologies for Fragment Screening
Computational Methods to Support Fragment-based Drug Discovery
Making FBDD Work in Academia
Site-Directed Fragment Discovery for Allostery
Fragment Screening in Complex Systems
Protein-Templated Fragment Ligation Methods: Emerging Technologies in Fragment-Based Drug Discovery
Successes from Fragment-based Drug Discovery
BACE Inhibitors
Epigenetics and Fragment-Based Drug Discovery
Discovery of Inhibitors of Protein–Protein Interactions Using Fragment-Based Methods
Fragment-Based Discovery of Inhibitors of Lactate Dehydrogenase A
FBDD Applications to Kinase Drug Hunting
An Integrated Approach for Fragment-Based Lead Discovery: Virtual, NMR, and High-Throughput Screening Combined with Structure-Guided Design. Application to the Aspartyl Protease Renin