D. McEachern

Discovery of Highly Efficacious CRBN-Based KRAS Degraders Targeting Cancers with KRAS G12D and G12V Mutations

KRAS G12D and G12V mutants account for >50% of human cancers carrying a mutated KRAS protein, and targeting KRAS proteins by induced protein degradation represents an attractive cancer therapeutic strategy. Herein, we present the design, synthesis, and evaluation of PROTAC KRAS degraders using a novel cereblon ligand,...