DI-1548

DI-1548 is a potent, selective, and irreversible covalent inhibitor of DCN1 (IC50 = 4.6 nM) . DI-1548 potently and selectively inhibits cullin 3 neddylation at nanomolar concentrations, and exhibits no obvious effect on the neddylation of other cullin members (including cullin 1, 2, 4A, 4B, and 5) . DI-1548 exhibits no cytotoxicity. DI-1548 covalently binds to DCN1, disrupting the DCN1-UBC12 interaction, causing the collapse of the neddylation complex, inactivating CRL3, leading to NRF2 accumulation and upregulation of its target genes, and ultimately protecting mice from liver damage. DI-1548 can be used in liver injury research[1].

Product Specifications

CAS Number

[2247060-97-3]

UNSPSC

12352005

Target

E1/E2/E3 Enzyme; Keap1-Nrf2

Related Pathways

Metabolic Enzyme/Protease; NF-κB

Applications

Metabolism-protein/nucleotide metabolism

Field of Research

Metabolic Disease

Smiles

C=C(CN1CCOCC1)C(NC[C@H](C2CCCCC2)NC([C@@H](NC(CC)=O)CC(SC3=C4)=NC3=CC=C4C(C)C)=O)=O

Molecular Formula

C32H47N5O4S

Molecular Weight

597.81

References & Citations

[1]Zhou H, et al. Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity. Nat Commun. 2021 May 11;12 (1) :2621.