2. Metabolic Enzyme/Protease NF-κB
  3. E1/E2/E3 Enzyme Keap1-Nrf2
  4. 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.

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DI-1548

DI-1548 Chemical Structure

CAS No. : 2247060-97-3

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DI-1548 Related Antibodies

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Description

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].

In Vitro

DI-1548 (1-1000 nM, 24 h) inhibits cullin 3 neddylation at concentrations as low as 1 nM and are approximately 1000 times more potent than DI-591 (HY-124602) in U2OS cells[1].
DI-1548 (0.3-1000 nM, 24 h) inhibits the neddylation of cullin 3 with over 1000-fold selectivity over other cullin members in various cell lines, including U2OS, MDA-MB-231, KYSE70, and HCT116[1].
DI-1548 (0-1000 nM, 72 h) shows no cytotoxicity in U2OS, MDA-MB-231, HCT116 and KYSE70 cells at concentrations up to 1000 nM[1].
DI-1548 (30 nM, 0-48 h) has fast kinetics in selective inhibition of the neddylation of cullin 3 over cullin 1[1].
DI-1548 (0.3-1000 nM, 1 h) selectively and potently stabilizes cellular DCN1 in a dose-dependent manner at nanomolar concentrations, with no observable effect on DCN3[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

DI-1548 Related Antibodies

Western Blot Analysis[1]

Cell Line: U2OS cells
Concentration: 1, 10, 100 and 1000 nM
Incubation Time: 24 h
Result: Reduced N-Cul3 levels at 1 nM and was approximately 1000 times more potent than DI-591.

Western Blot Analysis[1]

Cell Line: U2OS, MDA-MB-231, HCT116 and KYSE70 cells
Concentration: 0.3, 1, 3, 10, 30, 100, and 1000 nM
Incubation Time: 24 h
Result: Significantly reduced the level of N-CUL3 at concentrations as low as 0.3 nM, and achieved profound inhibition of the neddylation of cullin 3 at 1-3 nM.
Demonstrate over 300-fold greater potency than DI-591 across various cell lines.
Had no obvious effect on the neddylation of other cullin members that were examined, including cullin 1, 2, 4A, 4B, and 5 at concentrations up to 1000 nM.
Induced significant accumulation of NRF2 protein at concentrations as low as 0.3-1 nM, and was 100-1000 times more potent than DI-591.
Had no obvious effect on protein levels of KEAP1 and p62 in U2OS cells.
Had no effect on the levels of p21 and BIM proteins, substrates of CRL1, and CDT1, a substrate of CRL4A, at concentrations up to 1000 nM, consistent with its inability to inhibit neddylation of these cullin members.

Cell Viability Assay[1]

Cell Line: U2OS, MDA-MB-231, HCT116 and KYSE70 cells
Concentration: 0-1000 nM
Incubation Time: 72 h
Result: Showed no cytotoxicity in four cancer cell lines at concentrations up to 1000 nM.

Western Blot Analysis[1]

Cell Line: U2OS cells
Concentration: 30 nM
Incubation Time: 5 and 30 min,6, 24, and 48 h
Result: Inhibited the neddylation of cullin 3 within 5min but had no effect on the neddylation of cullin 1 with treatment time up to 48 h.

Western Blot Analysis[1]

Cell Line: U2OS cells
Concentration: 0.3, 1, 3, 10, 30, 100, and 1000 nM
Incubation Time: 1 h
Result: Enhanced the thermal stability of DCN1 protein in a dose-dependent manner at concentrations as low as 0.3 nM.
Exhibited over 1000-fold greater potency than DI-591 in enhancing the thermal stability of cellular DCN1 protein.
Showed no discernible effect on the thermal stability of cellular DCN3 protein at concentrations up to 1000 nM.
In Vivo

DI-1548 (25 mg/kg, i.p., once) elevates hepatic NRF2 protein levels in C57BL/6 WT mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male C57BL/6 WT mice (~8 weeks) [1]
Dosage: 25 mg/kg
Administration: i.p., once
Result: Induced robust upregulation of NRF2 protein in the mouse liver.
Produced a sustained PD effect in the liver despite being cleared from systemic circulation within 3 hours.
Molecular Weight

597.81

Formula

C32H47N5O4S
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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DI-1548 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

DI-15482247060-97-3DI1548DI 1548E1/E2/E3 EnzymeKeap1-Nrf2E1 activating enzymeE2 conjugating enzymeE3 ligating enzymeUbiquitin activating enzymeUbiquitin conjugating enzymeUbiquitin ligaseDCN1cullin 3 neddylationNRF2liver injuryU2OSMDA-MB-231HCT116KYSE70Inhibitorinhibitorinhibit

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