Ferumoxytol
Based on 1 Customer Validation
Ferumoxytol is an FDA-approved ultrasmall superparamagnetic iron oxide preparation and iron replacement agent that exerts selective activity against leukemia cells with low ferroportin expression. Ferumoxytol increases intracellular iron levels, induces reactive oxygen species (ROS) production via the Fenton reaction, and triggers oxidative stress and cell death. Ferumoxytol reduces disease burden in mouse models and patient-derived leukemia models. As an MRI contrast agent, Ferumoxytol enables imaging of vascular lesions, tumors and lymph nodes. Ferumoxytol can be used in research related to acute myeloid leukemia and blast-phase chronic myeloid leukemia.
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- Pureza : 95.00%
- No. CAS: 722492-56-0
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
Actividad biológica
Descripciòn
In Vitro
Ferumoxytol (24 h) significantly increases intracellular iron levels in human AML cell lines with low FPN expression, but exerts no such effect on human AML cell lines with high FPN expression[1].
Ferumoxytol (24-48 h) significantly reduces the viability of human acute myeloid leukemia (AML) cell lines and primary AML samples with low FPN expression, an effect mediated by oxidative stress, while human AML cell lines with high FPN expression are unaffected[1].
Ferumoxytol treatment upregulates the antioxidant stress response genes *SLC7A11*, *HMOX1* and *GCLC* in human AML cell lines with low FPN expression, and the extent of upregulation varies among different cell lines; in contrast, the expression of the aforementioned antioxidant genes shows no change in human AML cell lines with high FPN expression, and no upregulation of inflammatory cytokine genes is observed in any AML cell lines[1].
Ferumoxytol (24-48 h) significantly upregulates cytosolic and mitochondrial ROS levels in human acute myeloid leukemia (AML) cell lines with low FPN expression, and the increase in ROS levels correlates with decreased cell viability; in contrast, no significant change in ROS levels is observed in human AML cell lines with high FPN expression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
Ferumoxytol (5 mg/kg; intravenous injection; twice weekly; for 4 consecutive weeks) selectively reduces the bone marrow engraftment rate of FPN-low-expressing AML PDX, without affecting FPN-high-expressing AML PDX or normal hematopoietic cells, and simultaneously induces oxidative stress in FPN-low-expressing leukemia cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 6-8 weeks old, blast crisis chronic myeloid leukaemia induced by tail vein injection of 40 × 104 spleen cells carrying BCR-ABL/NUP98-HOXA9 oncogenes)[1]
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Dosage:3 mg/kg; 6 mg/kg
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Administration:i.v.; twice weekly; i.p.; three times weekly
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Result:Significantly reduced leukaemic blast percentage in peripheral blood, bone marrow, and spleen compared to saline controls.
Significantly lowered spleen index (spleen weight/body weight) compared to saline controls.
Significantly reduced peripheral blood leukaemic blast burden through day 21.
Increased median survival to 25 days compared to 17 days for saline controls.
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Animal Model:NOD/SCID; NSG (4-6 weeks old, acute myeloid leukaemia patient-derived xenografts established by tail vein injection of 2-5 million primary human AML cells with low ferroportin expression, following sub-lethal irradiation)[1]
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Dosage:5 mg/kg
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Administration:i.v.; twice weekly; 4 weeks
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Result:Significantly reduced human leukaemic cell engraftment percentage in bone marrow for three separate FPN-low AML PDX models (AML33, AML9, AML1) compared to saline controls.
Showed no reduction in FPN-high AML PDX or normal CD34+ cord blood xenografts.
Increased HMOX1 transcript levels in leukaemic cells from FPN-low AML PDXs by 2- to 6-fold, indicating increased oxidative stress.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 722492-56-0
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Appearance Liquid
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Color Light brown to brown
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SMILES
[Ferumoxytol]
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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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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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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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
Pureza y Documentación
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Ficha de datos (271 KB)
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SDS (419 KB)
- English - EN (419 KB)
- Français - FR (419 KB)
- Deutsch - DE (419 KB)
- Norwegian - NO (419 KB)
- Español - ES (419 KB)
- Swedish - SV (419 KB)
- Italian - IT (419 KB)
- Korean - KR (419 KB)
- Portuguese - PT (419 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Trujillo-Alonso V, et al. FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels. Nat Nanotechnol. 2019;14(6):616-622. [Content Brief]
[2]. Bashir MR, et al. Emerging applications for ferumoxytol as a contrast agent in MRI. J Magn Reson Imaging. 2015;41(4):884-898. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Keywords
- Ferumoxytol
- 722492-56-0
- Ferroptosis
- Reactive Oxygen Species (ROS)
- ferroportin-high leukaemia cells
- acute myeloid leukaemia
- FPN-low human AML cell lines
- reactive oxygen species
- normal haematopoietic cells
- Fenton reaction
- oxidative stress
- SLC7A11
- ferroportin-low leukaemia cells
- murine blast crisis chronic myeloid leukaemia models
- Inhibitor
- inhibitor
- inhibit