DI-591

• CAT Number: I017627
• CAS Number: 2245887-38-9
• Molecular Formula: C31H47N5O4S
• Molecular Weight: 585.80
• Purity: ≥95%
• Synonyms: (2S)-N-[(1S)-1-cyclohexyl-2-(3-morpholin-4-ylpropanoylamino)ethyl]-2-(propanoylamino)-3-(6-propan-2-yl-1,3-benzothiazol-2-yl)propanamide
• InChI: InChI=1S/C31H47N5O4S/c1-4-28(37)33-25(19-30-34-24-11-10-23(21(2)3)18-27(24)41-30)31(39)35-26(22-8-6-5-7-9-22)20-32-29(38)12-13-36-14-16-40-17-15-36/h10-11,18,21-22,25-26H,4-9,12-17,19-20H2,1-3H3,(H,32,38)(H,33,37)(H,35,39)/t25-,26+/m0/s1
• InChIKey: CNJKDQGPBAWNRY-IZZNHLLZSA-N
• SMILES: CCC(=O)NC(CC1=NC2=C(S1)C=C(C=C2)C(C)C)C(=O)NC(CNC(=O)CCN3CCOCC3)C4CCCCC4

DI-591 (CAT: I017627) is a potent, high-affinity, and cell-permeable inhibitor of the DCN1–UBC12 interaction, with Ki values of 12 nM (DCN1) and 10.4 nM (DCN2), showing >1000-fold selectivity over DCN3–5. It selectively inhibits neddylation of cullin 3 (CUL3) without significantly affecting other cullins. In KYSE70 cells, DI-591 disrupts DCN1–UBC12 association, while in THLE2 cells, it elevates NQO1 and HO1 mRNA, leading to increased HO1 protein expression. By stabilizing NRF2 protein through selective CUL3 inhibition, DI-591 serves as an excellent chemical probe for studying cullin-RING E3 ligase biology, NRF2 regulation, and therapeutic applications.

Reference

DI-591 (Compound 44) is a potent, high-affinity, and cell-permeable inhibitor of the DCN1–UBC12 interaction, with Ki_ii​ values of 12 nM (DCN1) and 10.4 nM (DCN2), showing >1000-fold selectivity over DCN3–5. It selectively inhibits neddylation of cullin 3 (CUL3) without significantly affecting other cullins. In KYSE70 cells, DI-591 disrupts DCN1–UBC12 association, while in THLE2 cells, it elevates NQO1 and HO1 mRNA, leading to increased HO1 protein expression. By stabilizing NRF2 protein through selective CUL3 inhibition, DI-591 serves as an excellent chemical probe for studying cullin-RING E3 ligase biology, NRF2 regulation, and therapeutic applications.