Necroptosis inducer 2
Necroptosis inducer 2 is a necroptosis inducer and copper chelator. Necroptosis inducer 2 chelates intracellular free copper ions, disrupts redox homeostasis, elevates ROS levels, disrupts mitochondrial membrane potential, and induces cancer cell necroptosis. Necroptosis inducer 2 upregulates the necroptosis markers p-MLKL and p-RIP3 expression. Necroptosis inducer 2 exhibits anti-tumor activity in mice. Necroptosis inducer 2 can be used for the research of cancer, such as triple-negative breast cancer.
For research use only. We do not sell to patients.
- Formula: C72H56Cl2N2O2P2
- Molecular Weight:1114.08
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
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RIPK3 |
Necroptosis inducer 2 (Compound 2d) (20 μM) binds selectively and strongly to Cu2+ and Cu+ in a cell-free system, with Ka values of 1.42 × 104/M and 7.33 × 103/M, respectively[1].
Necroptosis inducer 2 (48 h) potently inhibits the proliferation of MDA-MB-231, 4T1, HeLa, HT29, A2780, and U-2 OS cancer cells with IC50 values ranging from 4.1-10.6 μM, shows moderate activity against A549 cells (IC50 = 29.4 μM), and exhibits reduced toxicity toward non-cancerous MCF-10A cells (IC50 = 10.6 μM)[1].
Necroptosis inducer 2 (10 μM; 44 h treatment) has its cytotoxicity rescued in MDA-MB-231 cells by exogenous Cu2+, confirming copper chelation is essential for its antiproliferative activity[1].
Necroptosis inducer 2 (10-20 μM; 24 h) reduces intracellular chelatable copper levels in MDA-MB-231 cells in a concentration-dependent manner, as detected by CS1 confocal microscopy[1].
Necroptosis inducer 2 (20 μM; 24 h) rescues MDA-MB-231 cells from CuCl2-induced cytotoxicity, demonstrating potent copper-chelating activity in a cellular context[1].
Necroptosis inducer 2 (5-20 μM; 24 h) elevates intracellular ROS levels and disrupts mitochondrial membrane potential in MDA-MB-231 cells in vitro in a concentration-dependent manner, and this effect is reversed by exogenous Cu2+[1].
Necroptosis inducer 2 (10 μM; 44 h) induces cell death in MDA-MB-231 cells primarily via the necroptosis pathway, as only Necrostatin-1 (HY-15760) rescues cell viability[1].
Necroptosis inducer 2 (5-20 μM; 24 h) upregulates the necroptosis markers p-MLKL and p-RIP3 in MDA-MB-231 cells in vitro in a concentration-dependent manner[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 cells
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Concentration:5 μM, 10 μM, 20 μM
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Incubation Time:24 h
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Result:Caused a concentration-dependent upregulation of phosphorylated mixed lineage kinase domain-like (p-MLKL) and phosphorylated receptor-interacting protein kinase 3 (p-RIP3), key necroptosis markers.
Showed that markers for apoptosis, autophagy, and ferroptosis remained unchanged.
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Cell Line:MDA-MB-231 cells
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Concentration:10 μM, 20 μM
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Incubation Time:24 h
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Result:Caused a marked concentration-dependent increase in p-MLKL accumulation, providing direct visual evidence of necroptosis activation.
Necroptosis inducer 2 (5-20 mg/kg; intratumoral; 2 doses (day 1 and day 8 postmodeling)) exerts dose-dependent in vivo murine breast tumor growth inhibition, reaching 89.8% at 20 mg/kg with complete regression in some animals and no detectable hematological or systemic toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Breast cancer BALB/c mice (female, 4−6 weeks old, subcutaneous injection of 1 × 106 4T1 murine breast cancer cells)[1]
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Dosage:5 mg/kg
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Administration:intratumoral; 2 doses (day 1 and day 6 postmodeling)
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Result:Achieved a tumor inhibition rate of 36.3%.
Showed no significant body weight loss compared to the control group.
Revealed no obvious histopathological damage in major organs via H&E staining.
Induced extensive necrosis and structural disruption in tumor tissue via H&E staining.
Downregulated PCNA expression in tumor tissue via immunohistochemical analysis.
Caused a significant increase in p-MLKL staining in tumor tissue via immunohistochemical analysis.
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Animal Model:Breast cancer BALB/c mice (female, 4−6 weeks old, subcutaneous injection of 1 × 106 4T1 murine breast cancer cells)[1]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:intratumoral; 2 doses (day 1 and day 8 postmodeling)
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Result:Inhibited tumor growth in a dose-dependent manner, with tumor inhibition rates of 35.3%, 58.8%, and 89.8% at 5, 10, and 20 mg/kg, respectively.
Induced complete tumor regression in 2 out of 5 mice in the 20 mg/kg group.
Showed no significant body weight changes across all treated groups.
Revealed no hematological toxicity compared to the control group via red blood cell and platelet parameter analysis.
Chemical Information
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Molecular Weight 1114.08
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Formula C72H56Cl2N2O2P2
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SMILES
OC1=C(C=C(C=C1)C[P+](C2=CC=CC=C2)(C3=CC=CC=C3)C4=CC=CC=C4)/C=N/C5=C(C6=C(C=C5)C=CC=C6)C7=C8C(C=CC=C8)=CC=C7/N=C/C9=C(C=CC(C[P+](C%10=CC=CC=C%10)(C%11=CC=CC=C%11)C%12=CC=CC=C%12)=C9)O.[Cl-].[Cl-]
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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)
- Necroptosis inducer 2
- Necroptosis inducer2
- Necroptosis inducer-2
- Necroptosis
- Reactive Oxygen Species (ROS)
- Mitochondrial Metabolism
- Mixed Lineage Kinase
- RIP kinase
- necroptosis
- mitochondrial damage
- ovarian cancer
- osteosarcoma
- copper ions
- reactive oxygen species
- lung cancer
- triple-negative breast cancer
- colon cancer
- MDA-MB-231
- Inhibitor
- inhibitor
- inhibit