• Inhibits the interaction between XPF and ERCC1 in lung cancer cells.• Single agent activity and chemosensitivity to MMC and cisplatin in lung and colorectal cancer cells and radiosensitivity in lung cancer cells.• Shows synergy in BRCA1-defficient breast cancer cells by inducing synthetic lethality.IC50 = 0.79-3 μM. The gene discussed is ERCC4; the disease is lung cancer.