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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- CAS. Nr.: 2247060-97-3
- Formel: C32H47N5O4S
- Molecular Weight:597.81
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Help & FAQs
Biologische Aktivität
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.
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Cell Line:U2OS cells
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Concentration:1, 10, 100 and 1000 nM
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Incubation Time:24 h
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Result:Reduced N-Cul3 levels at 1 nM and was approximately 1000 times more potent than DI-591.
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Cell Line:U2OS, MDA-MB-231, HCT116 and KYSE70 cells
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Concentration:0.3, 1, 3, 10, 30, 100, and 1000 nM
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Incubation Time:24 h
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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.
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Cell Line:U2OS, MDA-MB-231, HCT116 and KYSE70 cells
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Concentration:0-1000 nM
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Incubation Time:72 h
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Result:Showed no cytotoxicity in four cancer cell lines at concentrations up to 1000 nM.
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Cell Line:U2OS cells
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Concentration:30 nM
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Incubation Time:5 and 30 min,6, 24, and 48 h
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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.
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Cell Line:U2OS cells
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Concentration:0.3, 1, 3, 10, 30, 100, and 1000 nM
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Incubation Time:1 h
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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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6 WT mice (~8 weeks) [1]
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Dosage:25 mg/kg
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Administration:i.p., once
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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.
Chemical Information
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CAS. Nr. 2247060-97-3
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Molecular Weight 597.81
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Formel C32H47N5O4S
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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
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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