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Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Design of compound libraries for fragment screening
Niklas Blomberg1, David A Cosgrove, Peter W Kenny
1AstraZeneca R&D Mölndal, Pepparedsleden 1, 431 83, Mölndal, Sweden.
Journal of Computer-Aided Molecular Design
|March 14, 2009
Summary
This study details fragment library design strategies for screening, using AstraZeneca
Area of Science:
- Drug Discovery and Medicinal Chemistry
- Computational Chemistry and Cheminformatics
Background:
- Fragment-based drug discovery (FBDD) relies on efficient screening libraries.
- Designing diverse and relevant compound libraries is crucial for successful screening campaigns.
Purpose of the Study:
- To illustrate approaches for designing generic fragment screening libraries.
- To describe AstraZeneca's proprietary tools and methods for library design.
- To demonstrate the application of the Core and Layer method for library generation.
Main Methods:
- Utilized a 20,000-compound generic fragment library and a 1,200-compound generic NMR screening library.
- Employed Foyfi fingerprints for compound characterization.
- Applied the Flush program for neighborhood analysis and BigPicker for selecting maximally diverse compound sets within the Core and Layer design framework.
Main Results:
- Demonstrated the practical application of the Core and Layer method using developed computational tools.
- Showcased the utility of Flush and BigPicker in constructing diverse fragment libraries.
- Presented strategies for partitioning libraries into manageable screening cocktails.
Conclusions:
- The described methods and tools facilitate the rational design of effective fragment screening libraries.
- The Core and Layer approach, combined with advanced computational methods, enables the creation of diverse and targeted compound collections for drug discovery.
