1. Apoptosis Metabolic Enzyme/Protease NF-κB Immunology/Inflammation
  2. Ferroptosis Glutathione Peroxidase Reactive Oxygen Species (ROS) Mitochondrial Metabolism
  3. Ferroptosis inducer-15

Ferroptosis inducer-15 is a ferroptosis inducer. Ferroptosis inducer-15 downregulates GPX4 expression, triggers lipid peroxidation via ROS accumulation, and disrupts mitochondrial membrane potential to drive ferroptosis. Ferroptosis inducer-15 increases splenic CD4+ T cell proportion, promotes CD8+ cytotoxic T cell tumor infiltration, and activates antitumor immune responses. Ferroptosis inducer-15 exerts antiproliferative activity against colorectal cancer cells and inhibits tumor growth in xenograft mice models without significant body weight loss. Ferroptosis inducer-15 can be used for the research of cancer, such as colorectal cancer.

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Ferroptosis inducer-15

Ferroptosis inducer-15 Chemical Structure

CAS No. : 3097756-33-4

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Description

Ferroptosis inducer-15 is a ferroptosis inducer. Ferroptosis inducer-15 downregulates GPX4 expression, triggers lipid peroxidation via ROS accumulation, and disrupts mitochondrial membrane potential to drive ferroptosis. Ferroptosis inducer-15 increases splenic CD4+ T cell proportion, promotes CD8+ cytotoxic T cell tumor infiltration, and activates antitumor immune responses. Ferroptosis inducer-15 exerts antiproliferative activity against colorectal cancer cells and inhibits tumor growth in xenograft mice models without significant body weight loss. Ferroptosis inducer-15 can be used for the research of cancer, such as colorectal cancer[1].

IC50 & Target[1]

GPX4

 

In Vitro

Ferroptosis inducer-15 (Compound 5k) (48 h) potently inhibits proliferation of HCT116 colorectal cancer cells with an IC50 of 0.81 μM, and shows variable antiproliferative activity against SW480, SW620, HT29, HepG2, and MCF-7 cells (IC50 = 2.43-21.84 μM)[1].
Ferroptosis inducer-15 induced cytotoxicity in HCT116 cells is dependent on ferroptosis, as indicated by reversal of cell death following co-treatment with ferroptosis-specific inhibitors[1].
Ferroptosis inducer-15 (1 μM; 24 h) significantly increases intracellular ROS, Fe2+ and lipid peroxidation levels in HCT116 colorectal cancer cells[1].
Ferroptosis inducer-15 (1 μM; 24 h) disrupts mitochondrial membrane potential and induces ferroptosis-associated mitochondrial morphological changes in HCT116 colorectal cancer cells[1].
Ferroptosis inducer-15 (0.5-2 μM; 24 h) downregulates SLC7A11, FTH1, and GPX4 expression and upregulates ACSL4 expression in HCT116 colorectal cancer cells, indicating induction of ferroptosis via the System Xc/GPX4 pathway[1].
Ferroptosis inducer-15 (1 μM) directly binds to GPX4 protein in HCT116 colorectal cancer cells, enhancing GPX4 stability under increasing temperatures (40-60°C)[1].
Ferroptosis inducer-15 (0.5-2 μM) reduces GPX4 mRNA expression in a concentration-dependent manner in HCT116 colorectal cancer cells[1].

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

Immunofluorescence[1]

Cell Line: HCT116 (colorectal adenocarcinoma)
Concentration: 1 μM
Incubation Time: 24 h
Result: Increased the fluorescence intensity DCFH-DA.

Western Blot Analysis[1]

Cell Line: HCT116 (colorectal adenocarcinoma)
Concentration: 0.5, 1, 2 μM
Incubation Time: 24 h
Result: Resulted in concentration-dependent downregulation of SLC7A11, FTH1, and GPX4 protein expression, and upregulation of ACSL4 protein expression in HCT116 cells.
In Vivo

Ferroptosis inducer-15 (Compound 5k) (25-50 mg/kg; i.p.; once every 2 days; 13 days) exhibits dose-dependent in vivo antitumor activity in a CT26 colorectal cancer xenograft model, achieving a 54.9% tumor inhibition rate at the 50 mg/kg dose, and activates antitumor immunity by increasing CD4+ and CD8+ T lymphocyte proportions without significant systemic toxicity[1].

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

Animal Model: BALB/c (5 weeks old, male/female, subcutaneous CT26 colon tumor cell implantation)[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: i.p.; once every 2 days; 13 days
Result: Achieved a tumor inhibition rate of 42.5%.
Achieved a tumor inhibition rate of 54.9%.
Did not induce significant body weight loss or obvious pathological changes in heart, liver, spleen, lung, or kidney tissues.
Increased the proportion of CD4+ T lymphocytes in the spleen by 1.3% and CD8+ T lymphocytes by 2.6% (at 25 mg/kg).
Increased the proportion of CD4+ T lymphocytes in the spleen by 6.2% and CD8+ T lymphocytes by 7.2% (at 50 mg/kg).
Molecular Weight

666.62

Formula

C31H41NO10Se

CAS No.
SMILES

O=C(O[C@@H]1O[C@@]2([H])[C@@]3(OO[C@](O2)(C)CC4)[C@]4([H])[C@H](C)CC[C@@]3([H])[C@H]1C)CCC(OCCCCN5[Se]C6=CC(OC)=CC=C6C5=O)=O

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