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Current perspectives in fragment-based lead discovery (FBLD)

It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protei...

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Detalles Bibliográficos
Autores principales: Lamoree, Bas, Hubbard, Roderick E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869234/
https://www.ncbi.nlm.nih.gov/pubmed/29118093
http://dx.doi.org/10.1042/EBC20170028
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author Lamoree, Bas
Hubbard, Roderick E.
author_facet Lamoree, Bas
Hubbard, Roderick E.
author_sort Lamoree, Bas
collection PubMed
description It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems.
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spelling pubmed-58692342018-04-05 Current perspectives in fragment-based lead discovery (FBLD) Lamoree, Bas Hubbard, Roderick E. Essays Biochem Review Articles It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems. Portland Press Ltd. 2017-11-08 /pmc/articles/PMC5869234/ /pubmed/29118093 http://dx.doi.org/10.1042/EBC20170028 Text en © 2017 The Author(s). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Review Articles
Lamoree, Bas
Hubbard, Roderick E.
Current perspectives in fragment-based lead discovery (FBLD)
title Current perspectives in fragment-based lead discovery (FBLD)
title_full Current perspectives in fragment-based lead discovery (FBLD)
title_fullStr Current perspectives in fragment-based lead discovery (FBLD)
title_full_unstemmed Current perspectives in fragment-based lead discovery (FBLD)
title_short Current perspectives in fragment-based lead discovery (FBLD)
title_sort current perspectives in fragment-based lead discovery (fbld)
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869234/
https://www.ncbi.nlm.nih.gov/pubmed/29118093
http://dx.doi.org/10.1042/EBC20170028
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