Screen millions of compounds simultaneously to accelerate lead compound identification

DNA-encoded libraries enable researchers to screen millions of barcoded compounds against biological targets in a single experiment, dramatically reducing cost, time, and storage requirements during early-stage drug discovery. DNA-Encoded Libraries: Principles and Applications provides scientists with the knowledge to leverage this technology across all phases of drug development. Written by experts from academia and the pharmaceutical industry, this volume addresses current methodologies and emerging applications.

This book delivers both a foundational overview of DNA-encoded library technology and detailed coverage of its diverse applications in pharmaceutical research. The text emphasizes recent advancements in the field and offers insight into future directions. Each chapter addresses practical considerations for integrating these methodologies into drug discovery workflows and screening programs, including:

• Detailed explanations of how DNA barcodes enable identification and tracking of promising small molecule compounds throughout the screening process
• Practical guidance on library design, synthesis strategies, and selection protocols for researchers implementing DNA-encoded library technology in their laboratories
• Coverage of affinity-based selection methods and data analysis approaches for identifying lead compounds from library screens against biological targets
• Discussion of emerging applications including fragment-based approaches, machine learning integration, and novel encoding strategies advancing the technology
• Insights from both academic researchers and industry scientists working at the forefront of DNA-encoded library development and application
  Postgraduates and researchers in drug discovery and pharmaceutical research will find this volume indispensable for understanding and applying DNA-encoded library technology. Whether experienced practitioners seeking to expand their methodology or newcomers integrating this approach into their research, readers will gain a thorough knowledge of both principles and practical applications.

Autorentext

Raphael M. Franzini, PhD, is a faculty member in the Department of Medicinal Chemistry at the University of Utah. After completing his PhD in Organic Chemistry at Stanford University and postdoctoral research at ETH Zurich, he established his research program focused on DNA-encoded libraries for drug discovery and bioorthogonal chemistry.

Moreno Wichert, PhD, is Principal Scientist of the DNA-Encoded Library Technology platform at Roche Innovation Center Basel, where he oversees all aspects of the technology and supports portfolio projects across disease and therapeutic areas. He completed his PhD at ETH Zurich in DNA-encoded self-assembling chemical library technology for de novo ligand discovery and tumor targeting applications.

Inhalt

List of Contributors

Preface

List of Abbreviations

Part I Principles of DELs

Chapter 1 The Dawn of DNA-Encoded Libraries

Chapter 2 The Architecture of DNA-Encoded Chemical Libraries: From Encoding Schemes to Display Geometry

Chapter 3 Aspects of Chemical Diversity in DNA-encoded Library Designs

Chapter 4 Toolbox for Synthesizing DNA-Encoded Chemical Libraries

Chapter 5 Selection Protocols for DNA-Encoded Libraries

Chapter 6 Informatics and DNA-Encoded Libraries: A Critical Symbiosis for Data Analysis and Workflow Acceleration

Chapter 7 Methods and Art of Hit Prioritization and Validation in DNA-Encoded Libraries

Chapter 8 DNA-Encoded Libraries and Machine Learning

Part II Applications of DELs

Chapter 9 Best Practices in DEL Hit Optimization

Chapter 10 Success Stories of DEL-Derived Hits

Chapter 11 DNA-Encoded Libraries for the Discovery of RNA-Targeting Drugs

Chapter 12 DNA-Encoded Library Selections on the Cell Surface and Inside Live Cells

Chapter 13 Enabling Molecular Glue Degraders and Proximity-Based Drugs with DNA-Encoded Chemical Libraries