| Autor: |
Silas Wurnig, Melina Vogt, Julian Hogenkamp, Niklas Dienstbier, Arndt Borkhardt, Sanil Bhatia, Finn K. Hansen |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Chemistry, Vol 11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2296-2646 |
| DOI: |
10.3389/fchem.2023.1219883 |
| Popis: |
Despite the early clinical promise, adverse events such as acquired resistance and dose-limiting toxicities have barred the widespread use of HSP90 inhibitors as anticancer drugs. A new approach involving proteolysis-targeting chimeras (PROTACs) to degrade the protein instead of inhibiting it may overcome these problems. In this work, we describe the design, synthesis, and evaluation of cereblon-recruiting geldanamycin-based HSP90 degraders based on the PROTAC technology. Our best degrader, 3a, effectively decreased HSP90α and HSP90β levels in cells utilizing the ubiquitin–proteasome pathway. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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