Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants - PubMed
5 days ago
- #KRAS inhibitor
- #Clinical trials
- #Cancer therapy
- Discovery of BBO-11818, a potent and selective noncovalent pan-KRAS inhibitor.
- BBO-11818 targets multiple KRAS mutants in both inactive (OFF) and active (ON) states.
- It binds in the Switch-II/Helix 3 pocket, disrupting effector binding.
- Demonstrates high-affinity binding to mutant KRAS with selectivity over NRAS and HRAS.
- Potently inhibits MAPK signaling and cellular viability in KRAS-driven lines.
- Shows tumor regressions in KRAS-mutant xenograft models.
- Enhanced efficacy in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.
- Currently in phase I clinical trials for KRAS-mutant colorectal, pancreatic, and lung cancers (NCT06917079).
- Addresses the need for inhibitors targeting KRASG12D and KRASG12V mutants.