Experiences in fragment-based drug discovery

Fragment-based drug discovery (FBDD) has become established in both industry and academia as an alternative approach to high-throughput screening for the generation of chemical leads for drug targets. In FBDD, specialised detection methods are used to identify small chemical compounds (fragments) th...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2012-05, Vol.33 (5), p.224-232
Main Authors: Murray, Christopher W, Verdonk, Marcel L, Rees, David C
Format: Article
Language:English
Subjects:
Advanced Basic Science
Amyloid Precursor Protein Secretases - chemistry
Animals
Aspartic Acid Endopeptidases - chemistry
Drug Discovery
HSP90 Heat-Shock Proteins - chemistry
Humans
Pharmaceutical Preparations - chemistry
Protein Conformation
Proto-Oncogene Proteins B-raf - chemistry
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Summary:Fragment-based drug discovery (FBDD) has become established in both industry and academia as an alternative approach to high-throughput screening for the generation of chemical leads for drug targets. In FBDD, specialised detection methods are used to identify small chemical compounds (fragments) that bind to the drug target, and structural biology is usually employed to establish their binding mode and to facilitate their optimisation. In this article, we present three recent and successful case histories in FBDD. We then re-examine the key concepts and challenges of FBDD with particular emphasis on recent literature and our own experience from a substantial number of FBDD applications. Our opinion is that careful application of FBDD is living up to its promise of delivering high quality leads with good physical properties and that in future many drug molecules will be derived from fragment-based approaches.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2012.02.006