CH091138

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 ; Blue: VHL E3 ligase ligand (HY-138678) ; Black: Linker; VHL E3 ligase ligand + Linker (HY-136006B) ).

C59H69FN10O6S

1065.31

OC1=CC(C=CC=C2C#C)=C2C(C3=C(F)C(N=C(OC[C@@H]4CCCN4CCCCCCC(N[C@H](C(N5[C@H](C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@@H](O)C5)=O)C(C)(C)C)=O)N=C8N9C[C@H]%10N[C@H](CC%10)C9)=C8C=N3)=C1

Apoptosis; PROTACs; Ras

K-Ras; von Hippel-Lindau (VHL)

Room temperature