Library Design Strategies to Accelerate Fragment-Based Drug Discovery

Nikolaj Sten Troelsen, Mads Hartvig Clausen*

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

Abstract

Fragment-based drug discovery (FBDD) has become an established approach for the generation of early lead candidates. However, despite its success and inherent advantages, hit-to-candidate progression for FBDD is not necessarily faster than for the traditional high-throughput screening. Thus, new technology-driven library design strategies have emerged as a means to facilitate more efficient fragment screening and/or subsequent fragment-to-hit chemistry. This minireview will discuss such strategies, which cover the use of labelled fragments for NMR spectroscopy, X-ray crystallographic screening of specialized fragments, covalent linkage for mass spectrometry, dynamic combinatorial chemistry, and fragments optimized for easy elaboration.
Original languageEnglish
JournalChemistry: A European Journal
Volume26
Issue number50
Pages (from-to)11391-11403
ISSN0947-6539
DOIs
Publication statusPublished - 2020

Keywords

  • Drug discovery
  • Fragment library
  • NMR spectroscopy
  • X-ray crystallography
  • Ligand design

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