BH-501242

BH-501242 is a novel, orally bioavailable, non-covalent pan-KRAS inhibitor developed by BlossomHill Therapeutics. It is designed to target the KRAS switch II pocket, enabling potent inhibition of a wide spectrum of KRAS mutations, including G12D, G12V, and G12C. As a "pan-KRAS on/off inhibitor," it binds to both the active (GTP-bound) and inactive (GDP-bound) states of the KRAS protein. Preclinical data presented at the AACR Annual Meeting 2026 demonstrated sub-nanomolar cellular activity and robust tumor regression in various xenograft models. The compound is characterized by a prolonged off-rate and pseudo-irreversible target engagement, positioning it as a mutation-agnostic therapeutic candidate for KRAS-driven malignancies such as non-small cell lung cancer and colorectal cancer.