As a result, DI-591/DI-404 cause the accumulation of NRF2, a CUL-3 substrate, in a dose-dependent manner in multiple cancer cell lines.456 However, DI-591/DI-404 fail to show any cytotoxicity in both human cancer cells at concentrations up to 20 μM, suggesting the dispensable functions of CRL3 activity in determining cell survival. The gene discussed is NFE2L2; the disease is cancer.