2. Apoptosis Metabolic Enzyme/Protease NF-κB Immunology/Inflammation
  3. Necroptosis TrxR Reactive Oxygen Species (ROS)
  4. Necroptosis inducer 1

Necroptosis inducer 1 is a necroptosis inducer. Necroptosis inducer 1 inhibits the activity of thioredoxin reductase (TrxR), elevates intracellular ROS levels, triggers ROS-mediated necroptosis, and induces necroptosis-dependent immunogenic cell death. Necroptosis inducer 1 inhibits tumor growth, remodels the tumor immune microenvironment, and exerts a synergistic effect with anti-PD-1 in animal models. Necroptosis inducer 1 is applicable to the research of colon cancer.

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Necroptosis inducer 1

Necroptosis inducer 1 Chemical Structure

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Description

Necroptosis inducer 1 is a necroptosis inducer. Necroptosis inducer 1 inhibits the activity of thioredoxin reductase (TrxR), elevates intracellular ROS levels, triggers ROS-mediated necroptosis, and induces necroptosis-dependent immunogenic cell death. Necroptosis inducer 1 inhibits tumor growth, remodels the tumor immune microenvironment, and exerts a synergistic effect with anti-PD-1 in animal models. Necroptosis inducer 1 is applicable to the research of colon cancer[1].

In Vitro

Necroptosis inducer 1 (Compound Au-1) (48 h) exhibits potent cytotoxicity in various cancer cell lines, with the highest activity against CT-26 cells (IC50 = 1.03 μM)[1].
Necroptosis inducer 1 (0.5-2 μM; 24-48 h) inhibits TrxR activity in CT-26 cells in vitro in a concentration- and time-dependent manner[1].
Necroptosis inducer 1 (0.5-2 μM; 24 h) induces concentration-dependent intracellular ROS accumulation in CT-26 cells[1].
Necroptosis inducer 1 (0.5-4 μM; 24-48 h) triggers ROS-mediated necroptosis, which acts as the dominant cell death pathway in CT-26 cells, characterized by upregulation of necroptosis-related proteins, increased Annexin V−/PI+ cells, PI uptake and LDH release[1].
Necroptosis inducer 1 (1-2 μM; 24 h) induces necroptosis-dependent immunogenic cell death (ICD) in CT-26 cells, which is characterized by concentration-dependent exposure of extracellular calreticulin (ecto-CRT), ATP release and HMGB1 release[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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In Vivo

Necroptosis inducer 1 (Compound Au-1) (10 mg/kg; i.v.; twice; 48 h interval between administrations) achieves a tumor growth inhibition rate (IRT) of 74.2% against orthotopic CT-26 tumors and 83.9% against distal CT-26 tumors, while maintaining mouse body weight[1].
Necroptosis inducer 1 (10 mg/kg; i.v.; once every two days for 24 days) achieves an IRT of 43.1%, while the IRT reaches 66.2% when combined with anti-PD-1. It remodels the tumor immune microenvironment by activating CD8+ and CD4+ helper T cells and reducing regulatory T cells, while maintaining the body weight of mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: BALB/c (4-week-old, sex not specified, subcutaneously inoculated with CT-26 cells to establish primary and distant tumors)[1]
Dosage: 10 mg/kg
Administration: i.v.; twice with 48-hour interval
Result: Achieved a 74.2% inhibition rate of tumor growth (IRT) in primary tumors.
Achieved an 83.9% IRT in distant tumors.
Maintained stable body weight throughout the treatment period.
Animal Model: BALB/c (4-week-old, sex not specified, subcutaneously inoculated with CT-26 cells to establish tumors reaching ~50 mm3)[1]
Dosage: 10 mg/kg
Administration: i.v.; every 48 hours
Result: Achieved a 43.1% IRT as monotherapy.
Achieved a 66.2% IRT in combination with anti-PD-1.
Maintained stable body weight throughout the treatment period.
Increased tumor-infiltrating CD3+CD8+ T cells from 0.83% to 3.57%.
Increased proportions of CD3+CD8+CD38+ T cells from 10.03% to 37.68% and CD3+CD8+Ki67+ T cells from 30.44% to 48.20%.
Increased percentages of CD8+ T cells expressing TNF-α to 17.66%, IFN-γ to 38.00%, and granzyme B to 23.64%.
Increased tumor-infiltrating CD3+CD4+ T cells from 0.79% to 5.25%.
Increased helper T (CD4+CD185+) cells from 7.63% to 18.18%.
Decreased immunosuppressive regulatory T (CD3+CD4+Foxp3+) cells from 18.83% to 8.60%.
Observed elevated CD3+CD8+ T cell infiltration in spleens, lymph nodes, and peripheral blood.
Molecular Weight

794.56

Formula

C25H28AuF6N2O2PS2
SMILES

F[P-](F)(F)(F)(F)F.CCCCN(C1=[S][Au+]2(C3=CC=CC=C3C4=[N]2C=CC5=C4C=C6C(OCO6)=C5)S1)CCCC
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Keywords:

Necroptosis inducer 1Necroptosis inducer1Necroptosis inducer-1NecroptosisTrxRReactive Oxygen Species (ROS)Thioredoxin Reductasethioredoxin reductaseanti-PD-1 therapyCD8+ T cellsCD4+ helper T cellsreactive oxygen speciescolon carcinomanecroptosisimmunogenic cell deathregulatory T cellsCT-26 cellsInhibitorinhibitorinhibit

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