1. Apoptosis Metabolic Enzyme/Protease NF-κB Immunology/Inflammation
  2. Ferroptosis Glutathione Peroxidase Reactive Oxygen Species (ROS)
  3. Ferroptosis inducer-8

Ferroptosis inducer-8 is a ferroptosis inducer with high selectivity for other cell death mechanism. Ferroptosis inducer-8 induces ferroptosis by affecting ACSL4, GPX4, and FTH1, thereby disrupting intracellular iron homeostasis and the GSH/GPX4 antioxidant defense system, ultimately leading to the accumulation of lipid peroxidation. Ferroptosis inducer-8 also induces ROS production. Ferroptosis inducer-8 inhibits tumor growth and can be used for research of triple-negative breast cancer (TNBC).

Ferroptosis inducer-8 is a ferroptosis inducer with high selectivity for other cell death mechanism. Ferroptosis inducer-8 induces ferroptosis by affecting ACSL4, GPX4, and FTH1, thereby disrupting intracellular iron homeostasis and the GSH/GPX4 antioxidant defense system, ultimately leading to the accumulation of lipid peroxidation. Ferroptosis inducer-8 also induces ROS production. Ferroptosis inducer-8 inhibits tumor growth and can be used for research of triple-negative breast cancer (TNBC).

For research use only. We do not sell to patients.

Ferroptosis inducer-8

Ferroptosis inducer-8 Chemical Structure

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Description

Ferroptosis inducer-8 is a ferroptosis inducer with high selectivity for other cell death mechanism. Ferroptosis inducer-8 induces ferroptosis by affecting ACSL4, GPX4, and FTH1, thereby disrupting intracellular iron homeostasis and the GSH/GPX4 antioxidant defense system, ultimately leading to the accumulation of lipid peroxidation. Ferroptosis inducer-8 also induces ROS production. Ferroptosis inducer-8 inhibits tumor growth and can be used for research of triple-negative breast cancer (TNBC)[1].

In Vitro

Ferroptosis inducer-8 binds to GPX4 and reduces the thermal stability of GPX4[1].
Ferroptosis inducer-8 (Compound B23) (48 h) shows cytotoxicity in tumor cells with IC50s of 0.08 μM (MCF-7), 0.04 μM (MDA-MB-231), 0.04 μM (MDA-MB-468), 0.05 μM (HT29), 2.81 μM (A549), 0.06 μ(MPC-3), and 2.23 μM for normal cell (MCF-10A)[1].
Ferroptosis inducer-8 (1 μM, 48 h ) selectively induces ferroptosis of MDA-MB-231 and MDA-MB-468 cells, instead of other cell death mechanisms such as apoptosis, necrosis, or autophagy[1].
Ferroptosis inducer-8 (20-60 nM, 7 h) induces disturbances in iron metabolism, exacerbates lipid peroxidation, and induces ROS production (10 h) in MDA-MB-231 cells[1].
Ferroptosis inducer-8 (20-60 nM, 8 h) upregulates expression of ACSL4, downregulates FTH1 and GPX4 in MDA-MB-231 cells[1].

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

Cell Viability Assay[1]

Cell Line: MDA-MB-231 and MDA-MB-468 cells
Concentration: 1 μM, co-incubation with Z-VAD-FMK (10 μM), Necrostatin-1 (10 μM) or 3-MA (5 mM); co-incubation with the ferroptosis inhibitors Fer-1 ( 1 μM), DFO (200 μM)), GSH (5 mM) or NAC (5 mM)
Incubation Time: Pretreated with various cell death inhibitors for 30 min, then co-incubation for 48 h
Result: Inhibited cell viability and the effect was rescued by Fer-1 ( HY-100579), Deferoxamine (DFO) (HY-B1625)), GSH (HY-D0187) or NAC (HY-B0215).
The cytotoxicity could not rescued by Z-VAD-FMK (HY-16658B), Necrostatin-1 (HY-15760), 3-MA (HY-19312).

Western Blot Analysis[1]

Cell Line: MDA-MB-231 cells
Concentration: 20, 40, 60 nM
Incubation Time: 8 h
Result: Upregulated expression of ACSL4, downregulates FTH1 and GPX4 in MDA-MB-231 cells, and the modulatory effects were partially restored by Fer-1 (1 μM).
In Vivo

Ferroptosis inducer-8 (1-4 mg/kg, i.v., daily for 21 days) shows antitumor efficacy in MDA-MB-231 xenograft models[1].

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

Animal Model: MDA-MB-231 xenograft model established in BALB/C nude mice (4 weeks)[1]
Dosage: 1, 2, 4 mg/kg
Administration: Daily tail vein injection (i.v.), at the corresponding doses for 21 days.
Result: Inhibited tumor growth in a concentration-dependent manner, with the tumor growth inhibition (TGI) rate of 78.46% (4 mg/kg), which was significantly higher than that in the positive control group (4 mg/kg RSL3 (HY-100218A), TGI = 27.21%).
Had lower toxicity (higher body weight) than RSL3 at high doses.
Showed no apparent toxicity to the hearts, livers, spleens, lungs or kidneys (H&E staining).
Molecular Weight

486.34

Formula

C22H25Cl2NO7

SMILES

O=C(OC)C1=CO[C@@H](OC)[C@]2([H])C(CN(C3=CC(OC)=C(Cl)C(OC)=C3)C(CCl)=O)=CC[C@@]21[H]

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Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Ferroptosis inducer-8
Cat. No.:
HY-174345
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