Discovery of selective platelet-derived growth factor receptor-beta (PDGFR-?) bifunctional small-molecule degrader br

Proteolysis-targeting chimeras (PROTACs) is a promising strategy for treatment of various diseases by degrading of disease-related proteins in recent years. Up to now, most PROTAC molecules are mainly aimed at the degradation of intracellular proteins, but many disease-related proteins are membrane or extracellular proteins. The targeted degradation of membrane proteins would be an attractive and general strategy for discovery of novel PROTACs. Herein, we report the development of multi-targeted kinase inhibitor sorafenib-based PROTACs, they can selectively degrade platelet-derived growth factor receptor beta (PDGFR-beta). We provide a method that can be used to degrade cell membrane proteins. To our knowledge, this study also is the first report of PROTAC induced PDGFR-beta degradation in cancer cells.

Automated summary

PROTACs is a promising strategy for treatment of various diseases by degrading disease-related proteins. Most PROTAC molecules are aimed at the degradation of intracellular proteins, but many disease-related proteins are membrane or extracellular proteins. This study reports the development of multi-targeted kinase inhibitor sorafenib-based PROTACs, which can selectively degrade PDGFR-beta, providing a method to degrade cell membrane proteins. It is also the first report of PROTAC induced PDGFR-beta degradation in cancer cells.