BBO-10203 (E5872-GRP)

BBO-10203 inhibits PI3Kα and KRASG12C by covalently binding to Cys242 in the PI3Kα RAS-Binding Domain. It inhibits both GTP-bound and GDP-bound KRASG12C states, with IC50 and EC50 values of 0.031 nM and 0.02 nM respectively. This compound interferes with RAS-PI3Kα interaction, suppressing RAS-dependent PI3Kα activation. It decreases pERK levels, inhibits cell proliferation, and causes G1 phase arrest and apoptosis. BBO-10203 has potential applications in breast cancer, colorectal cancer, and non-small cell lung cancer research.