MS9427 is a potent PROTAC EGFR degrader, demonstrating high affinity for EGFR with dissociation constants (K d s) of 7.1 nM for the wild-type (WT) EGFR and 4.3 nM for the L858R mutant EGFR, indicating selective degradation of the mutant over the WT EGFR. This degradation occurs through both ubiquitin/proteasome system (UPS) and autophagy/lysosome pathways. Furthermore, MS9427 effectively inhibits the proliferation of non-small cell lung cancer (NSCLC) cells, positioning it as a potential therapeutic agent in anticancer research [1].

EGFR L858R:4.3 nM (Kd), EGFR (WT):7.1 nM (Kd)