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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] | | [https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and has sparked the development of a growing number of thalidomide derivatives. Here, we probe the chemical space of cereblon binding beyond such derivatives and work out a simple set of chemical requirements, delineating the metaclass of cereblon effectors. We report co-crystal structures for a diverse set of compounds, including commonly used pharmaceuticals, but also find that already minimalistic cereblon-binding moieties might exert teratogenic effects in zebrafish. Our results may guide the design of a post-thalidomide generation of therapeutic cereblon effectors and provide a framework for the circumvention of unintended cereblon binding by negative design for future pharmaceuticals.
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| Chemical Ligand Space of Cereblon.,Boichenko I, Bar K, Deiss S, Heim C, Albrecht R, Lupas AN, Hernandez Alvarez B, Hartmann MD ACS Omega. 2018 Sep 14;3(9):11163-11171. doi: 10.1021/acsomega.8b00959. , eCollection 2018 Sep 30. PMID:31459225<ref>PMID:31459225</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5oh9" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
