bbo-10203

BBO-10203 is a first-in-class, orally bioavailable small molecule that acts as a selective "breaker" of the interaction between RAS proteins (HRAS, NRAS, KRAS) and phosphoinositide 3-kinase alpha (PI3Kα). By covalently binding to the RAS-binding domain of PI3Kα, it prevents oncogenic RAS from activating PI3Kα and downstream AKT signaling in tumors. This mechanism allows for potent inhibition of tumor growth in cancers driven by mutations in KRAS or PIK3CA or by HER2 amplification/overexpression. Notably, BBO-10203 achieves this without inducing hyperglycemia because insulin signaling does not depend on RAS-mediated PI3Kα activation. Preclinical studies have shown significant antitumor activity across multiple tumor types and enhanced efficacy when combined with other targeted therapies such as CDK4/6 inhibitors, estrogen receptor antagonists, HER2 inhibitors (e.g., trastuzumab), and KRAS-G12C inhibitors[4][5][6]. The drug is currently being evaluated in Phase 1 clinical trials for advanced solid tumors including HER2-positive breast cancer, HR-positive/HER2-negative breast cancer, KRAS mutant colorectal cancer (CRC), and KRAS mutant non-small cell lung cancer (NSCLC)[1][8].

Other names

Compound 758Compound758Compound-758