SHOC2–RAS PPI-IN-1

SHOC2-RAS PPI-IN-1 (compound 6) is a non-covalent competitive inhibitor that disrupts the SHOC2-RAS protein-protein interaction. It exhibits an IC50 of 0.048 μM and a KD of 0.065 μM against NRASQ61R. The compound inhibits the SMP phosphatase complex, resulting in elevated CRAFS259 phosphorylation and subsequent blockade of the MAPK signaling pathway (evidenced by reduced pMEK and pERK levels) . This inhibition induces tumor cell cycle arrest and apoptosis. SHOC2-RAS PPI-IN-1 serves as a research tool for investigating NRASQ61R-mutant malignancies including melanoma and colorectal cancer.