Encoding BRAF inhibitor functions in protein degraders
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Updated: Sep 5, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Daniel S J Miller1, Sabine A Voell2, Izidor Sosič3
1Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research London SW7 3RP UK.
Abstract:
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.
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