Fragment-based Drug Discovery: Lessons and Outlook

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. INDICE: # 01 The Role of Fragment–Based Approaches in Lead Finding. # 02 Selecting the Right Targets for FBDD. # 03 Enumeration of Chemical Fragment Space . # 04 Ligand Efficiency Metrics and their Use in Fragment Optimizations. # 05 Strategies for Fragment Library Design. # 06 The Synthesis of Biophysical Methods In Support of Robust Fragment–Based Lead Discovery. # 07 Differential Scanning Fluorimetry as Part of a Biophysical Screening Cascade . # 08 Emerging Technologies for Fragment Screening. # 09 Computational Methods to Support Fragment Based Drug Discovery. # 10 Making FBDD Work in Academia. # 11 Site–Directed Fragment Discovery for Allostery. # 12 Fragment Screening in Complex Systems. # 13 Protein–Templated Fragment Ligation Methods: Emerging Technologies in Fragment–Based Drug Discovery . # 14 BACE Inhibitors. # 15 Epigenetics and Fragment Based Drug Discovery. # 16 Discovery of Inhibitors of Protein ? Protein Interactions Using Fragment–Based Methods. # 17 Fragment–Based Discovery of Inhibitors of Lactate Dehydrogenase A. # 18 FBDD Applications to Kinase Drug Hunting. # 19 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..

• ISBN: 978-3-527-33775-0
• Editorial: Wiley VCH
• Encuadernacion: Cartoné
• Páginas: 472
• Fecha Publicación: 23/12/2015
• Nº Volúmenes: 1
• Idioma: Inglés