CSN5-IN-3
CSN5-IN-3 (Compound 30) is a CSN5 inhibitor with an IC50 of 0.58 μM. CSN5-IN-3 inhibits the enzymatic activity of CSN5, leading to increased accumulation of NEDD8-Cul1 and promoting the degradation of PD-L1. CSN5-IN-3 downregulates Bcl-2, and upregulates P53 and Cleaved caspase-3. CSN5-IN-3 exhibits anticancer activity against triple-negative breast cancer.
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- Formel: C27H31N5O
- Molecular Weight:441.57
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
Caspase 3 |
Bcl-2 |
CSN5 0.58 μM (IC50) |
In Vitro
CSN5-IN-3 (20 min) acts as a potent CSN5 inhibitor in cell-free fluorescence polarization assays, with an IC50 of 0.58 μM[1].
CSN5-IN-3 (72 h) potently inhibits the viability of MDA-MB-231 cells, with an IC50 value of 2.1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:2.5-20 μM (direct treatment); 10 μM (following 2 h preincubation with MG132 or MLN4924)
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Incubation Time:12 h
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Result:Dose-dependently increased NEDD8-Cul1 protein levels while not altering CSN5 expression.
Dose-dependently reduced PD-L1 protein levels.
Dose-dependently upregulated P53, and cleaved caspase-3 protein levels.
Dose-dependently downregulated Bcl-2 protein levels.
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Cell Line:MDA-MB-231 human triple-negative breast cancer cells
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Concentration:1-10 μM
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Incubation Time:24 h
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Result:Caused no significant change in G0/G1 phase cell percentage at 1 μM.
Increased G0/G1 phase cell percentage by 9.6% compared to control at 5 μM (p < 0.01).
Increased G0/G1 phase cell percentage by 18.3% compared to control at 10 μM (p < 0.001).
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 4 weeks old, triple-negative breast cancer subcutaneous xenograft model)[1]
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Dosage:8 mg/kg; 16 mg/kg
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Administration:i.p.; every 3 days; 21 days
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Result:Achieved 68.3% tumor growth inhibition (TGI) at 8 mg/kg.
Achieved 89.3% tumor growth inhibition (TGI) at 16 mg/kg.
Showed no mortality in either treatment group.
Exhibited no significant body weight changes in the low-dose group; caused a slight temporary body weight decrease but no significant end-of-study weight loss in the high-dose group.
Reduced PD-L1 and Ki67 expression, and increased P21 expression in excised tumors via immunohistochemical analysis.
Chemical Information
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Molecular Weight 441.57
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Formel C27H31N5O
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SMILES
CC1=CC=C(C(C2=CC(OC)=CC=C2)=C1)C3=CC4=C(N3)N=CC=C4NCCN5CCNCC5
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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.
Protokoll
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)