| Autor: |
Zhengnian Li, Han‐Yuan Liu, Zhixiang He, Antara Chakravarty, Ryan P. Golden, Zixuan Jiang, Inchul You, Hong Yue, Katherine A. Donovan, Guangyan Du, Jianwei Che, Jason Tse, Isaac Che, Wenchao Lu, Eric S. Fischer, Tinghu Zhang, Nathanael S. Gray, Priscilla L. Yang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 11, Iss 40, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202405829 |
| Popis: |
Abstract Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E‐degraders are developed by linking two previously reported E‐binding small molecules, GNF‐2, and CVM‐2‐12‐2, to a glutarimide‐based recruiter of the CRL4CRBN ligase to effect proteosome‐mediated degradation of the E protein. ZXH‐2‐107 (based on GNF‐2) is an E‐degrader with ABL inhibitory activity while ZXH‐8‐004 (based on CVM‐2‐12‐2) is a selective and potent E‐degrader. These two compounds provide proof of concept that difficult‐to‐drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class of direct‐acting antiviral drugs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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