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Using Fragment-Based Approaches to Discover New Antibiotics

Fragment-based lead discovery has emerged over the past two decades as a successful approach to generate novel lead candidates in drug discovery programs. The two main advantages over conventional high-throughput screening (HTS) are more efficient sampling of chemical space and tighter control over...

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Detalles Bibliográficos
Autores principales: Lamoree, Bas, Hubbard, Roderick E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024353/
https://www.ncbi.nlm.nih.gov/pubmed/29923463
http://dx.doi.org/10.1177/2472555218773034
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author Lamoree, Bas
Hubbard, Roderick E.
author_facet Lamoree, Bas
Hubbard, Roderick E.
author_sort Lamoree, Bas
collection PubMed
description Fragment-based lead discovery has emerged over the past two decades as a successful approach to generate novel lead candidates in drug discovery programs. The two main advantages over conventional high-throughput screening (HTS) are more efficient sampling of chemical space and tighter control over the physicochemical properties of the lead candidates. Antibiotics are a class of drugs with particularly strict property requirements for efficacy and safety. The development of novel antibiotics has slowed down so much that resistance has now evolved against every available antibiotic drug. Here we give an overview of fragment-based approaches in screening and lead discovery projects for new antibiotics. We discuss several successful hit-to-lead development examples. Finally, we highlight the current challenges and opportunities for fragment-based lead discovery toward new antibiotics.
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spelling pubmed-60243532018-07-11 Using Fragment-Based Approaches to Discover New Antibiotics Lamoree, Bas Hubbard, Roderick E. SLAS Discov Review Fragment-based lead discovery has emerged over the past two decades as a successful approach to generate novel lead candidates in drug discovery programs. The two main advantages over conventional high-throughput screening (HTS) are more efficient sampling of chemical space and tighter control over the physicochemical properties of the lead candidates. Antibiotics are a class of drugs with particularly strict property requirements for efficacy and safety. The development of novel antibiotics has slowed down so much that resistance has now evolved against every available antibiotic drug. Here we give an overview of fragment-based approaches in screening and lead discovery projects for new antibiotics. We discuss several successful hit-to-lead development examples. Finally, we highlight the current challenges and opportunities for fragment-based lead discovery toward new antibiotics. SAGE Publications 2018-06-20 2018-07 /pmc/articles/PMC6024353/ /pubmed/29923463 http://dx.doi.org/10.1177/2472555218773034 Text en © 2018 Society for Laboratory Automation and Screening http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Lamoree, Bas
Hubbard, Roderick E.
Using Fragment-Based Approaches to Discover New Antibiotics
title Using Fragment-Based Approaches to Discover New Antibiotics
title_full Using Fragment-Based Approaches to Discover New Antibiotics
title_fullStr Using Fragment-Based Approaches to Discover New Antibiotics
title_full_unstemmed Using Fragment-Based Approaches to Discover New Antibiotics
title_short Using Fragment-Based Approaches to Discover New Antibiotics
title_sort using fragment-based approaches to discover new antibiotics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024353/
https://www.ncbi.nlm.nih.gov/pubmed/29923463
http://dx.doi.org/10.1177/2472555218773034
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