Design, synthesis, and structural optimization of novel pan-KRAS degrader for the treatment of KRAS-mutant pancreatic cancer.
KRAS, a frequently mutated oncogene, has been demonstrated to harbor multiple mutant variants. Although KRAS G12C inhibitors have been successfully approved for clinical use, their efficacy remains limited by acquired resistance and narrow patient eligibility. Here, we leveraged the proteolysis-targeting chimera (PROTA...