Encoding BRAF inhibitor functions in protein degraders.
![Thumbnail](/bitstream/handle/internal/5136/RSC%20Med%20Chem%202022%20d2md00064d.pdf.jpg?sequence=6&isAllowed=y)
View/ Open
Date
2022-06-22Author
Miller, DSJ
Voell, SA
Sosič, I
Proj, M
Rossanese, OW
Schnakenburg, G
Gütschow, M
Collins, I
Steinebach, C
Type
Journal Article
Metadata
Show full item recordAbstract
Various BRAF kinase inhibitors were developed to treat cancers carrying the BRAFV600E mutation. First-generation BRAF inhibitors could lead to paradoxical activation of the MAPK pathway, limiting their clinical usefulness. Here, we show the development of two series of BRAFV600E-targeting PROTACs and demonstrate that the exchange of the inhibitor scaffold from vemurafenib to paradox-breaker ligands resulted in BRAFV600E degraders that did not cause paradoxical ERK activation.
Collections
Research team
Medicinal Chemistry 2
Language
eng
Date accepted
2022-05-05
Citation
RSC Medicinal Chemistry
Publisher
ROYAL SOC CHEMISTRY