Bumped pomalidomide-based PROTACs
Pomalidomide is an E3 ligase recruiter exploited by PROTACs to degrade target proteins, but its application is hampered by the off-target degradation of other vital endogenous zinc finger (ZF) proteins. Now, the off-target ZF binding of pomalidomide-based PROTACs is evaluated by a high-throughput im...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01125-2 |
| _version_ | 1797275580534620160 |
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| author | Huijuan Guo |
| author_facet | Huijuan Guo |
| author_sort | Huijuan Guo |
| collection | DOAJ |
| description | Pomalidomide is an E3 ligase recruiter exploited by PROTACs to degrade target proteins, but its application is hampered by the off-target degradation of other vital endogenous zinc finger (ZF) proteins. Now, the off-target ZF binding of pomalidomide-based PROTACs is evaluated by a high-throughput imaging screening platform, and minimization of off-target degradation as well as enhanced potency are achieved through selective functionalization at the C5 position of the phthalimide ring. |
| first_indexed | 2024-03-07T15:16:30Z |
| format | Article |
| id | doaj.art-df435b957eed4c8a8df3e49008e010b2 |
| institution | Directory Open Access Journal |
| issn | 2399-3669 |
| language | English |
| last_indexed | 2024-03-07T15:16:30Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj.art-df435b957eed4c8a8df3e49008e010b22024-03-05T17:55:27ZengNature PortfolioCommunications Chemistry2399-36692024-02-01711210.1038/s42004-024-01125-2Bumped pomalidomide-based PROTACsHuijuan Guo0Communications ChemistryPomalidomide is an E3 ligase recruiter exploited by PROTACs to degrade target proteins, but its application is hampered by the off-target degradation of other vital endogenous zinc finger (ZF) proteins. Now, the off-target ZF binding of pomalidomide-based PROTACs is evaluated by a high-throughput imaging screening platform, and minimization of off-target degradation as well as enhanced potency are achieved through selective functionalization at the C5 position of the phthalimide ring.https://doi.org/10.1038/s42004-024-01125-2 |
| spellingShingle | Huijuan Guo Bumped pomalidomide-based PROTACs Communications Chemistry |
| title | Bumped pomalidomide-based PROTACs |
| title_full | Bumped pomalidomide-based PROTACs |
| title_fullStr | Bumped pomalidomide-based PROTACs |
| title_full_unstemmed | Bumped pomalidomide-based PROTACs |
| title_short | Bumped pomalidomide-based PROTACs |
| title_sort | bumped pomalidomide based protacs |
| url | https://doi.org/10.1038/s42004-024-01125-2 |
| work_keys_str_mv | AT huijuanguo bumpedpomalidomidebasedprotacs |