SE486-11
SE486-11 is an orally active USP5 inhibitor. SE486-11 increases free polyubiquitin chains and promotes the ubiquitination and degradation of MYCN. The combination of SE486-11 with SAHA (HY-10221) synergistically induces Apoptosis. SE486-11 can be used in research related to MYCN-driven neuroblastoma.
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- No. CAS: 305333-99-7
- Fòrmula: C26H20N4O
- Peso molecular:404.46
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Descripciòn
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Kelly | IC50 |
34.4 μM
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Cytotoxicity against human neuroblastoma Kelly cells by Alamar Blue cell viability assay.
Cytotoxicity against human neuroblastoma Kelly cells by Alamar Blue cell viability assay.
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37060785 |
In Vitro
SE486-11 (1:5 ratio with SAHA) binds purified full-length USP5 protein with a Kd of 159 nM, over 100-fold higher affinity than SAHA alone[1].
SE486-11 does not exhibit measurable binding affinity to purified full-length USP5 protein in an MST assay, as a dose-response kinetic curve could not be fitted[2].
SE486-11 (5-10 µM; 48-72 h) causes synergistic cytotoxicity in MYCN-amplified neuroblastoma cells (SK-N-BE(2)-C, Kelly, CHP134, IMR-32, LAN-1) and MDA-MB-231 breast cancer cells, with limited effects on normal human fibroblasts (WI-38, MRC-5)[1].
SE486-11 (5 µM; 24-72 h) reduces clonogenic colony formation (number and size) in MYCN-amplified SK-N-BE(2)-C and Kelly neuroblastoma cells[1].
SE486-11 inhibits the viability of SK-N-BE(2)-C and Kelly human neuroblastoma cells with IC50 values of 41.8 μM and 34.4 μM, respectively[2].
SE486-11 enhances the effectiveness of HDAC inhibitors in neuroblastoma cells by increasing MYCN ubiquitination via modulation of USP5[2].
SE486-11 (5 µM; 72 h) synergistically induces apoptosis in MYCN-amplified SK-N-BE(2)-C and Kelly neuroblastoma cells, but not in normal WI-38 and MRC-5 human fibroblasts[1].
SE486-11 (5 µM; 48 h) increases mitochondrial depolarisation in MYCN-amplified SK-N-BE(2)-C and Kelly neuroblastoma cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 breast cancer cells, SK-N-BE(2)-C and Kelly MYCN-amplified neuroblastoma cells, WI-38 and MRC-5 normal human fibroblasts, panel of MYCN-amplified (CHP134, IMR-32, LAN-1) and non-amplified (SH-SY5Y, SK-N-AS, SK-N-FI) neuroblastoma cells
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Concentration:10 µM (with 1.9 µM SAHA, MDA-MB-231 cells); 5 µM (with 1 µM SAHA, SK-N-BE(2)-C, Kelly, WI-38, MRC-5 cells and neuroblastoma cell panel)
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Incubation Time:48 h (MDA-MB-231 cells and neuroblastoma cell panel); 72 h (SK-N-BE(2)-C, Kelly, WI-38, MRC-5 cells)
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Result:Reduced MDA-MB-231 cell viability to <40% when used with 1.9 µM SAHA for 48 h, while maintaining >70% viability when used alone.
Caused synergistic cytotoxicity (combination index <1) and reduced cell viability far below single agents in MYCN-amplified neuroblastoma cells when used with 1 µM SAHA for 72 h.
Exhibited limited cytotoxicity in normal WI-38 and MRC-5 fibroblasts when used with 1 µM SAHA for 72 h.
Caused the greatest viability reduction in MYCN-amplified neuroblastoma lines compared to non-amplified lines when used with 1 µM SAHA for 48 h.
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Cell Line:SK-N-BE(2)-C and Kelly MYCN-amplified neuroblastoma cells, WI-38 and MRC-5 normal human fibroblasts
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Concentration:5 µM (with 1 µM SAHA)
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Incubation Time:72 h
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Result:Significantly increased the percentage of cells in early and late apoptosis in SK-N-BE(2)-C and Kelly cells compared to single agents or DMSO control.
Did not induce apoptosis in normal WI-38 and MRC-5 fibroblasts.
In Vivo
Combination treatment with SE486-11 (30 mg/kg; p.o.; daily; 7 days) and SAHA reduces tumour size and lowers MYCN, USP5, and proliferation marker PCNA levels in MYCN-transgenic zebrafish with neuroblastoma[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:TH-MYCN+/+ (female, 3 weeks old, transgenic spontaneously developing neuroblastoma)[1]
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Dosage:30 mg/kg
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Administration:i.p.; 5 days on/2 days off; 21 days
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Result:Reduced tumour formation to the extent that no tumour tissue remained for histopathological analysis.
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Animal Model:dβh:EGFP-MYCN (0.5-1.5 years old, transgenic GFP-positive neuroblastoma)[1]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Caused a reduction in GFP-positive tumour size from day 1 to day 7.
Reduced MYCN, USP5, and PCNA protein levels in tumour tissue compared with vehicle control.
Chemical Information
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No. CAS 305333-99-7
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Peso molecular 404.46
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Fòrmula C26H20N4O
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SMILES
CC1=C(C#N)C2=NC3=C(C=CC=C3)N2C(NC4=CC=C(O)C=C4)=C1CC5=CC=CC=C5
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
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Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SE486-11 Related Classifications
HY-187705 Related Classifications
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