BBO-8520 represents a groundbreaking first-in-class covalent inhibitor that uniquely targets both the active (ON) and inactive (OFF) states of KRAS-G12C. Through comprehensive global cysteine proteome analysis, BBO-8520 demonstrates exceptional binding specificity to KRAS-G12C, showcasing a remarkable selectivity of over 100-fold compared to wild-type KRAS and other mutant isoforms. Notably, BBO-8520 exhibits no detectable activity against N-RAS or H-RAS, underscoring its precision in selectively inhibiting KRAS-G12C. This distinctive profile positions BBO-8520 as a promising therapeutic candidate for addressing KRAS-G12C-driven cancers, offering a novel approach to targeting this historically challenging oncogenic mutation.
