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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1019636/full |
| _version_ | 1828341241731874816 |
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| author | Cassandra Kennedy Katherine McPhie Katrin Rittinger |
| author_facet | Cassandra Kennedy Katherine McPhie Katrin Rittinger |
| author_sort | Cassandra Kennedy |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T23:09:52Z |
| format | Article |
| id | doaj.art-8d8ca31eb6ef4e9bab2cb712527c4ecd |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-13T23:09:52Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-8d8ca31eb6ef4e9bab2cb712527c4ecd2022-12-22T02:25:36ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-09-01910.3389/fmolb.2022.10196361019636Targeting the ubiquitin system by fragment-based drug discoveryCassandra KennedyKatherine McPhieKatrin RittingerThe 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.https://www.frontiersin.org/articles/10.3389/fmolb.2022.1019636/fullubiquitindrug discoveryfragment-based drug discoverychemical toolsubiquitination |
| spellingShingle | Cassandra Kennedy Katherine McPhie Katrin Rittinger Targeting the ubiquitin system by fragment-based drug discovery Frontiers in Molecular Biosciences ubiquitin drug discovery fragment-based drug discovery chemical tools ubiquitination |
| 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 | ubiquitin drug discovery fragment-based drug discovery chemical tools ubiquitination |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1019636/full |
| work_keys_str_mv | AT cassandrakennedy targetingtheubiquitinsystembyfragmentbaseddrugdiscovery AT katherinemcphie targetingtheubiquitinsystembyfragmentbaseddrugdiscovery AT katrinrittinger targetingtheubiquitinsystembyfragmentbaseddrugdiscovery |