Library Design Strategies To Accelerate Fragment-Based Drug Discovery |
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Authors: | Dr Nikolaj S Troelsen Prof Dr Mads H Clausen |
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Institution: | Center for Nanomedicine and Theranostics, Department of Chemistry, Technical University of Denmark, Kemitorvet 207, 2800 Kongens Lyngby, Denmark |
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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 that of 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 discusses such strategies, which cover the use of labeled 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. |
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Keywords: | drug discovery fragment libraries ligand design NMR spectroscopy X-ray crystallography |
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