Fragment-Based Drug Discovery: Volume 47 (Drug Discovery Series) - Hardcover

Hardcover

ISBN 10: 1849739080 ISBN 13: 9781849739085

Publisher: Royal Society of Chemistry, 2015

Synopsis

This book will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in drug discovery techniques.

About this title

About the Author

Daniel A. Erlanson is the co-founder of Carmot Therapeutics, a small-molecule drug discovery company applying fragment-based approaches to a variety of therapeutic targets. Prior to Carmot, Dr. Erlanson spent a decade developing fragment-based drug discovery technologies at Sunesis Pharmaceuticals, where he worked since the company's inception. Before joining Sunesis, he was an NIH postdoctoral fellow with Dr. James A. Wells at Genentech. Dr. Erlanson earned his Ph.D. in chemistry from Harvard University in the laboratory of Gregory L. Verdine and his B.A. in chemistry from Carleton College. Wolfgang Jahnke is a Senior Research at the Novartis Institutes for Biomedical Research in Basel, Switzerland, where he leads the Fragment-Based Screening technology platform. He has received several honors, among them the appointment as Scientific Expert, and the Leading Scientist Award. Dr. Jahnke received his PhD from the TU Munchen, working with Horst Kessler on the development and application of novel NMR methods. Prior to joining Novartis, he worked with Peter Wright at the Scripps Research Institute in La Jolla.

From the Back Cover

Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique.

This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.

From the Inside Flap

Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique.

This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.

Excerpt. © Reprinted by permission. All rights reserved.

Fragment-Based Drug Discovery

By Steven Howard, Chris Abell

The Royal Society of Chemistry

Copyright © 2015 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-84973-908-5

Contents

Personal Essay: Fragments in the Blogosphere Daniel A. Erlanson, 
Personal Essay: Adventures and Experiences in Fragment-Based Drug Discovery Martin J. Drysdale, 
Chapter 1 Different Flavours of Fragments Chris Abell and Claudio Dagostin, 
Chapter 2 Getting the Most Value from Your Screens: Advances in Hardware, Software, and Methodologies to Enhance Surface Plasmon Resonance Based Fragment Screening and Hit-to-Lead Support Anthony M. Giannetti, Houston N. Gilbert, Donald P. Huddler, Mac Reiter, Chris Strande, Keith E. Pitts, and Brandon J. Bravo, 
Chapter 3 Applications of NMR in Fragment-Based Drug Design Isabelle Krimm, 
Chapter 4 Current Status and Future Direction of Fragment-Based Drug Discovery: A Computational Chemistry Perspective Ian D. Wall, Michael M. Hann, Andrew R. Leach, and Stephen D. Pickett, 
Chapter 5 Fragment Screening of G Protein-Coupled Receptors Miles Congreve and Robert Cooke, 
Chapter 6 Fragment-Based Lead Discovery Applied to Protein–Protein Interactions Roderick E. Hubbard, 
Chapter 7 Fragment-Based Discovery of Allosteric Ligands Steven Howard, 
Chapter 8 Fragment-Based Discovery of Antibacterials Christina Spry and Anthony G. Coyne, 
Chapter 9 Exploring Fragment Screening and Optimization Strategies Using Acetylcholine-Binding Protein Ewald Edink, Gerdien E. de Kloe, and Iwan J. P. de Esch, 
Chapter 10 Fragment-Based Approaches to Epigenetic Targets Chun-wa Chung and Paul Bamborough, 
Subject Index, 

CHAPTER 1

Different Flavours of Fragments

CHRIS ABELL AND CLAUDIO DAGOSTIN

1.1Fragment-Based Drug Discovery

Fragment-based drug discovery is becoming a powerful technology in the arsenal of the pharmaceutical companies to aid discovery of new small-molecule therapeutics, establish the druggability of biological targets, and discover alternative inhibition sites on already established ones. With the market approval of Zelboraf® (Vemurafenib – the first drug discovered via fragment-based drug discovery) the approach has a measure of validation and interest in the field continues to grow.

Fragments are small molecules that may become parts of a larger molecule, but in some cases were fragments of known drugs, that have been used as starting points to find new inhibitors for different biological targets. A fragment is a small, typically aromatic, organic molecule of molecular weight <250 Da, which is very soluble and chemically stable. The use of such small molecules at the beginning of a medicinal chemistry program allows an effective exploration of chemical space and a more rational design of the final molecule through iterations guided by structural knowledge of the site of binding. In the best cases, the approach can offer a less expensive and faster route to potent and better quality lead compounds compared with more traditional approaches such as high-throughput screening (HTS) of higher molecular weight compounds.

1.2 Different Types of Fragments

Views on the composition of fragment libraries have evolved over time. Some libraries were assembled by taking known drugs and dissecting them into fragments or by computationally finding diverse fragments. It was apparent from the start that solubility would be very important because of the concentrations used for screening (often tens of mM). Another key criterion was lack of reactive groups altho

Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 2015
• Language: English
• ISBN 10: 1849739080
• ISBN 13: 9781849739085
• Binding: Hardcover
• Number of pages: 314
• Editor: Steven Howard