CH091138

Description

CH091138 is a potent and selective KRASG12D PROTAC degrader with DC50s of 148.3 nM in HeLa cells and 469.8 nM in AsPC-1 cells. CH091138 selectively degrades exogenous and endogenous KRASG12D but not KRASWT or other KRAS mutants G12C/G12S/G12V , depending on the VHL-mediated ubiquitin-proteasome system. CH091138 exhibits potent anti-tumor activity and induces cancer cell apoptosis. CH091138 can be used for the studies of pancreatic cancer and colon cancer. Pink: KRASG12D ligand HY-175144 ; Blue: VHL E3 ligase ligand HY-138678 ; Black: Linker; VHL E3 ligase ligand + Linker HY-136006B .