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Targeting the ubiquitin system by fragment-based drug discovery
The ubiquitin system contains a wealth of potential drug targets for many diseases and conditions, including neurodegenerative, immune, metabolic and developmental diseases, as well as multiple cancers. Despite years of research, relatively few clinical inhibitors or specific chemical probes for pro...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580268/ https://www.ncbi.nlm.nih.gov/pubmed/36275626 http://dx.doi.org/10.3389/fmolb.2022.1019636 |
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author | Kennedy, Cassandra McPhie, Katherine Rittinger, Katrin |
author_facet | Kennedy, Cassandra McPhie, Katherine Rittinger, Katrin |
author_sort | Kennedy, Cassandra |
collection | PubMed |
description | The ubiquitin system contains a wealth of potential drug targets for many diseases and conditions, including neurodegenerative, immune, metabolic and developmental diseases, as well as multiple cancers. Despite years of research, relatively few clinical inhibitors or specific chemical probes for proteins within the ubiquitin system exist, with many interesting target proteins yet to be explored. Fragment-based drug discovery (FBDD) offers efficient and broad coverage of chemical space with small libraries, using covalent and non-covalent approaches. Coupled with advances in structural biology and proteomics, FBDD now provides a thorough screening platform for inhibitor discovery within the ubiquitin system. In this mini review, we summarise the current scope of FBDD and how it has been applied to ubiquitin-activating (E1), ubiquitin-conjugating (E2), ubiquitin ligase (E3) and deubiquitinating (DUB) enzymes. We also discuss the newest frontiers of FBDD and how they could be applied to enable inhibitor and novel chemical probe discovery and provide functional insight into the ubiquitin system. |
format | Online Article Text |
id | pubmed-9580268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95802682022-10-20 Targeting the ubiquitin system by fragment-based drug discovery Kennedy, Cassandra McPhie, Katherine Rittinger, Katrin Front Mol Biosci Molecular Biosciences The ubiquitin system contains a wealth of potential drug targets for many diseases and conditions, including neurodegenerative, immune, metabolic and developmental diseases, as well as multiple cancers. Despite years of research, relatively few clinical inhibitors or specific chemical probes for proteins within the ubiquitin system exist, with many interesting target proteins yet to be explored. Fragment-based drug discovery (FBDD) offers efficient and broad coverage of chemical space with small libraries, using covalent and non-covalent approaches. Coupled with advances in structural biology and proteomics, FBDD now provides a thorough screening platform for inhibitor discovery within the ubiquitin system. In this mini review, we summarise the current scope of FBDD and how it has been applied to ubiquitin-activating (E1), ubiquitin-conjugating (E2), ubiquitin ligase (E3) and deubiquitinating (DUB) enzymes. We also discuss the newest frontiers of FBDD and how they could be applied to enable inhibitor and novel chemical probe discovery and provide functional insight into the ubiquitin system. Frontiers Media S.A. 2022-09-27 /pmc/articles/PMC9580268/ /pubmed/36275626 http://dx.doi.org/10.3389/fmolb.2022.1019636 Text en Copyright © 2022 Kennedy, McPhie and Rittinger. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Kennedy, Cassandra McPhie, Katherine Rittinger, Katrin Targeting the ubiquitin system by fragment-based drug discovery |
title | Targeting the ubiquitin system by fragment-based drug discovery |
title_full | Targeting the ubiquitin system by fragment-based drug discovery |
title_fullStr | Targeting the ubiquitin system by fragment-based drug discovery |
title_full_unstemmed | Targeting the ubiquitin system by fragment-based drug discovery |
title_short | Targeting the ubiquitin system by fragment-based drug discovery |
title_sort | targeting the ubiquitin system by fragment-based drug discovery |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580268/ https://www.ncbi.nlm.nih.gov/pubmed/36275626 http://dx.doi.org/10.3389/fmolb.2022.1019636 |
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