Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs
Abstract PROteolysis-Targeting Chimeras (PROTACs) are an emerging class of molecules capable of inducing a forced approximation between a protein of interest (POI) and an E3 ligase enzyme (e.g., Cereblon), leading to the degradation of the POI by the cell’s own machinery. Although in early stages of...
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Nature Portfolio
2025-07-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01598-9 |
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| author | André T. S. Vicente Sara P. S. P. Moura Jorge A. R. Salvador |
| author_facet | André T. S. Vicente Sara P. S. P. Moura Jorge A. R. Salvador |
| author_sort | André T. S. Vicente |
| collection | DOAJ |
| description | Abstract PROteolysis-Targeting Chimeras (PROTACs) are an emerging class of molecules capable of inducing a forced approximation between a protein of interest (POI) and an E3 ligase enzyme (e.g., Cereblon), leading to the degradation of the POI by the cell’s own machinery. Although in early stages of development, PROTACs’ unique mechanisms of action offer a novel therapeutic strategy, which has attracted growing interest worldwide. Cereblon-based PROTACs are the most studied class of PROTACs and have been actively researched in recent years for the treatment of different diseases, from cancer to neurological disorders, with some of them already in clinical trials. In this review, we provide a comprehensive and critical analysis covering the recent advances, potential challenges and future prospects regarding the design and synthesis, as well as pre- and clinical evaluation of cereblon-based PROTACs. By integrating insights from drug discovery and development, a broad yet in-depth discussion is given to guide future research on cereblon-based PROTACs. |
| format | Article |
| id | doaj-art-cd0fca60c9bd440b90f6a1aff8c8b7fe |
| institution | DOAJ |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-cd0fca60c9bd440b90f6a1aff8c8b7fe2025-08-20T03:04:26ZengNature PortfolioCommunications Chemistry2399-36692025-07-018114310.1038/s42004-025-01598-9Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACsAndré T. S. Vicente0Sara P. S. P. Moura1Jorge A. R. Salvador2Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of CoimbraLaboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of CoimbraLaboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of CoimbraAbstract PROteolysis-Targeting Chimeras (PROTACs) are an emerging class of molecules capable of inducing a forced approximation between a protein of interest (POI) and an E3 ligase enzyme (e.g., Cereblon), leading to the degradation of the POI by the cell’s own machinery. Although in early stages of development, PROTACs’ unique mechanisms of action offer a novel therapeutic strategy, which has attracted growing interest worldwide. Cereblon-based PROTACs are the most studied class of PROTACs and have been actively researched in recent years for the treatment of different diseases, from cancer to neurological disorders, with some of them already in clinical trials. In this review, we provide a comprehensive and critical analysis covering the recent advances, potential challenges and future prospects regarding the design and synthesis, as well as pre- and clinical evaluation of cereblon-based PROTACs. By integrating insights from drug discovery and development, a broad yet in-depth discussion is given to guide future research on cereblon-based PROTACs.https://doi.org/10.1038/s42004-025-01598-9 |
| spellingShingle | André T. S. Vicente Sara P. S. P. Moura Jorge A. R. Salvador Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs Communications Chemistry |
| title | Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs |
| title_full | Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs |
| title_fullStr | Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs |
| title_full_unstemmed | Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs |
| title_short | Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs |
| title_sort | synthesis biological evaluation and clinical trials of cereblon based protacs |
| url | https://doi.org/10.1038/s42004-025-01598-9 |
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