Based upon DI-591, the Wang group further designed a class of covalent DCN1 inhibitors and discovered two potent, selective and covalent DCN1 inhibitors, designated as DI-1548 and DI-1859.458 Both inhibitors inhibit CUL-3 neddylation in cancer cells at low nanomolar concentrations with 2–3 orders of magnitude more potent than DI-591. This evidence concerns the gene CUL3 and cancer.