dCE-2
dCE-2 is a CBP/EP300 PROTAC degrader with a DC50 of 40 nM against CBP. dCE-2 forms a ternary complex with the bromodomains of CBP/EP300 and the CRBN E3 ligase, driving proteasomal degradation of CBP/EP300 via positive cooperativity. dCE-2 is applicable to research related to multiple myeloma, prostate cancer, and neuroblastoma.
(Pink: EP300/CBP ligand (HY-161960); Blue: Cereblon ligand (HY-103596); Black: linker (HY-130715)).
For research use only. We do not sell to patients.
- Formula: C44H47N9O6
- Molecular Weight:797.90
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
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CBP 40 nM (DC50) |
Cereblon |
dCE-2 exhibits moderate binary binding affinity (KD = 1300 nM) for purified CBP-BRD in a cell-free BROMOscan competition assay, while no detectable binding activity is observed for purified EP300-BRD[1].
dCE-2 exhibits moderate binary binding to purified CBP-BRD (IC50 = 150 nM); in a cell-free TR-FRET competition assay, its binding is enhanced (IC50 = 45 nM) with positive cooperativity (α = 3.4)[1] in the presence of purified CRBN.
dCE-2 (0.01-5 μM; 2-24 h) potently degrades CBP (DC50 = 40 nM) and EP300 in LP1 multiple myeloma cells via the PROTAC mechanism, with the maximum degradation effect observed after 16-24 h of treatment[1].
dCE-2 (1 μM; 16 h) degrades CBP in MM1S, LNCaP and SH-SY5Y cancer cell lines, with a sustained bias toward EP300[1].
dCE-2 (0.001-10 μM) inhibits the proliferation of multiple myeloma cell lines LP1 (GI50 = 1.5 μM) and MM1S (GI50 = 35 nM)[1].
dCE-2 (1 μM; 16 h) downregulates CBP, EP300 and MYC (but not BRD4) in LP1 and MM1S cells, as determined by global proteomic analysis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LP1 multiple myeloma cells
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Concentration:1-5 μM (16 h); 0.01-1 μM (16 h); 1 μM (2-24 h); 10 μM compound 2, 10 μM GNE-781, 50 μM pomalidomide (pretreatment for 1 h followed by 1 μM dCE-2); 1 μM MLN4924 (pretreatment for 2 h followed by 1 μM dCE-2); 10 μM MG132 (pretreatment for 30 min followed by 1 μM dCE-2)
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Incubation Time:2-24 h; 1 h (pretreatment with compound 2/GNE-781/pomalidomide); 2 h (pretreatment with MLN4924); 30 min (pretreatment with MG132)
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Result:Left 16% of CBP and 43% of EP300 remaining at 5 μM for 16 h.
Robustly degraded CBP/EP300 at 1 μM for 16 h.
Abrogated CBP/EP300 degradation when cells were pretreated with CBP/EP300-BRD binders, pomalidomide, MLN4924, or MG132.
Showed a DC50 of 40 nM for CBP degradation after 16 h of dose-response testing.
Initiated CBP/EP300 degradation within 2 h, with maximal degradation achieved by 16-24 h in time-course testing.
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Cell Line:MM1S multiple myeloma cells, LNCaP prostate cancer cells, SH-SY5Y neuroblastoma cells
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Concentration:1 μM
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Incubation Time:16 h
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Result:Robustly degraded CBP in all three cell lines.
Showed consistent bias for CBP degradation over EP300 across all lines.
Chemical Information
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Molecular Weight 797.90
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Formula C44H47N9O6
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SMILES
O=C(N1C2CCC(NC2=O)=O)C3=CC=CC(NCCCCCCCCCCC(NC4=CC(C5=NN(C)C=C5)=CC(C(NC6=CC=CC7=C6C=C(C)N=N7)=O)=C4)=O)=C3C1=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)