protac k-ras degrader-4

PROTAC K-Ras Degrader-4 (Compound 4) is a proteolysis-targeting chimera (PROTAC) molecule designed to selectively degrade oncogenic mutants of K-Ras, effectively degrading KRASG12D in the GP5d cell line and KRASG12V in SW620 cells with DC50 of 1 nM and 13 nM, respectively; it concomitantly inhibits the downstream MAPK signaling pathway and represents a novel therapeutic strategy for cancer research targeting previously undruggable Ras mutations.

K-Ras ligand-Linker Conjugate 4 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker, responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. It has the potential to be used in synthesizing PROTAC K-Ras Degrader-1, which shows a degradation efficacy of ≥70% in SW1573 cells[1].