Ferrostatin-1 (Fer-1)Ferroptosis inhibitor, erastin-induced CAS# 347174-05-4 |
- Erastin
Catalog No.:BCC4497
CAS No.:571203-78-6
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 347174-05-4 | SDF | Download SDF |
PubChem ID | 4068248 | Appearance | Powder |
Formula | C15H22N2O2 | M.Wt | 262.35 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 150 mg/mL (571.76 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | ethyl 3-amino-4-(cyclohexylamino)benzoate | ||
SMILES | CCOC(=O)C1=CC(=C(C=C1)NC2CCCCC2)N | ||
Standard InChIKey | UJHBVMHOBZBWMX-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C15H22N2O2/c1-2-19-15(18)11-8-9-14(13(16)10-11)17-12-6-4-3-5-7-12/h8-10,12,17H,2-7,16H2,1H3 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Selective inhibitor of erastin induced ferroptosis (EC50 = 60 nM). Specifically inhibits Ras selective lethal compound -induced death, but not cell death induced by other oxidative lethal compounds and apoptosis-inducing agents. Inhibits ferroptosis in cancer cells; also inhibits glutamate-induced cell death in organotypic rat brain slices. Prevents erastin induced accumulation of cytosolic and lipid reactive oxygen species. |
Ferrostatin-1 (Fer-1) Dilution Calculator
Ferrostatin-1 (Fer-1) Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.8117 mL | 19.0585 mL | 38.117 mL | 76.234 mL | 95.2925 mL |
5 mM | 0.7623 mL | 3.8117 mL | 7.6234 mL | 15.2468 mL | 19.0585 mL |
10 mM | 0.3812 mL | 1.9059 mL | 3.8117 mL | 7.6234 mL | 9.5293 mL |
50 mM | 0.0762 mL | 0.3812 mL | 0.7623 mL | 1.5247 mL | 1.9059 mL |
100 mM | 0.0381 mL | 0.1906 mL | 0.3812 mL | 0.7623 mL | 0.9529 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Ferrostatin-1 is a selective inhibitor of ferroptosis.
Ferroptosis is a regulated, oxidative, nanapoptotic cell death, Ferrostatin-1 has been founded as a potent inhibitor of it. Fer-1 can attenuate oxidative, iron-dependent cancer cell death through blocking cystine import and glutathione production. It had been reported to prevent Huntington's disease cellular models to death by inhibiting lipid peroxidation.[1]
Reference:
1. Skouta, R., et al., Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc, 2014. 136(12): p. 4551-6.
- Incensole acetate
Catalog No.:BCN3830
CAS No.:34701-53-6
- 1-Indanamine
Catalog No.:BCN2246
CAS No.:34698-41-4
- TCS 2510
Catalog No.:BCC7853
CAS No.:346673-06-1
- Dehydrodeguelin
Catalog No.:BCN4778
CAS No.:3466-23-7
- Cyperotundone
Catalog No.:BCN8339
CAS No.:3466-15-7
- Amoxicillin Sodium
Catalog No.:BCC4947
CAS No.:34642-77-8
- 1-Methoxycarbonyl-beta-carboline
Catalog No.:BCN5282
CAS No.:3464-66-2
- 2-Benzoyloxy-3-hydroxynortropane
Catalog No.:BCN1872
CAS No.:34622-25-8
- Maltohexaose
Catalog No.:BCN6710
CAS No.:34620-77-4
- Maltopentaose
Catalog No.:BCN8421
CAS No.:34620-76-3
- Maltotetraose
Catalog No.:BCN6709
CAS No.:34612-38-9
- 5-hydroxypyrazine-2-carboxylic acid
Catalog No.:BCC1311
CAS No.:34604-60-9
- ITX3
Catalog No.:BCC6066
CAS No.:347323-96-0
- Sodium usnate
Catalog No.:BCN8376
CAS No.:34769-44-3
- Z-Asp(OBzl)-OH
Catalog No.:BCC2791
CAS No.:3479-47-8
- H-D-Met-OH
Catalog No.:BCC2997
CAS No.:348-67-4
- H-Tyr(Bzl)-OMe.HCl
Catalog No.:BCC3132
CAS No.:34805-17-9
- Boc-Met(O)-OH
Catalog No.:BCC3425
CAS No.:34805-21-5
- BAY 57-1293
Catalog No.:BCC4050
CAS No.:348086-71-5
- 8-Acetonyldihydroavicine
Catalog No.:BCN3303
CAS No.:348098-59-9
- Marilactone
Catalog No.:BCN7363
CAS No.:34818-17-2
- 4'-Demethyleucomin
Catalog No.:BCN5283
CAS No.:34818-83-2
- DL-Dithiothreitol
Catalog No.:BCC7586
CAS No.:3483-12-3
- Bz-Tyr-Oet
Catalog No.:BCC3122
CAS No.:3483-82-7
MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells.[Pubmed:28250973]
Cell Death Discov. 2017 Feb 27;3:17013.
Regulation of cell death is potentially a powerful treatment modality for intractable diseases such as neurodegenerative diseases. Although there have been many reports about the possible involvement of various types of cell death in neurodegenerative diseases, it is still unclear exactly how neurons die in patients with these diseases, thus treatment strategies based on cell death regulation have not been established yet. To obtain some insight into the mechanisms of cell death involved in neurodegenerative diseases, we studied the effect of 1-methyl-4-phenylpyridinium (MPP+) on the human neuroblastoma cell line SH-SY5Y (a widely used model of Parkinson's disease). We found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including Ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease.
Lipoxygenase inhibitors protect acute lymphoblastic leukemia cells from ferroptotic cell death.[Pubmed:28595877]
Biochem Pharmacol. 2017 Sep 15;140:41-52.
Ferroptosis has recently been identified as a mode of programmed cell death. However, little is yet known about the signaling mechanism. Here, we report that lipoxygenases (LOX) contribute to the regulation of RSL3-induced ferroptosis in acute lymphoblastic leukemia (ALL) cells. We show that the glutathione (GSH) peroxidase 4 (GPX4) inhibitor RSL3 triggers lipid peroxidation, production of reactive oxygen species (ROS) and cell death in ALL cells. All these events are impeded in the presence of Ferrostatin-1 (Fer-1), a small-molecule inhibitor of lipid peroxidation. Also, lipid peroxidation and ROS production precede the induction of cell death, underscoring their contribution to cell death upon exposure to RSL3. Importantly, LOX inhibitors, including the selective 12/15-LOX inhibitor Baicalein and the pan-LOX inhibitor nordihydroguaiaretic acid (NDGA), protect ALL cells from RSL3-stimulated lipid peroxidation, ROS generation and cell death, indicating that LOX contribute to ferroptosis. RSL3 triggers lipid peroxidation and cell death also in FAS-associated Death Domain (FADD)-deficient cells which are resistant to death receptor-induced apoptosis indicating that the induction of ferroptosis may bypass apoptosis resistance. By providing new insights into the molecular regulation of ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in ALL.
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid-Induced AKI.[Pubmed:27352622]
J Am Soc Nephrol. 2017 Jan;28(1):218-229.
AKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)-induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor-interacting protein kinase 3 (RIPK3) and mixed lineage domain-like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.
On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death.[Pubmed:28386601]
ACS Cent Sci. 2017 Mar 22;3(3):232-243.
Ferroptosis is a form of regulated necrosis associated with the iron-dependent accumulation of lipid hydroperoxides that may play a key role in the pathogenesis of degenerative diseases in which lipid peroxidation has been implicated. High-throughput screening efforts have identified Ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent inhibitors of ferroptosis - an activity that has been ascribed to their ability to slow the accumulation of lipid hydroperoxides. Herein we demonstrate that this activity likely derives from their reactivity as radical-trapping antioxidants (RTAs) rather than their potency as inhibitors of lipoxygenases. Although inhibited autoxidations of styrene revealed that Fer-1 and Lip-1 react roughly 10-fold more slowly with peroxyl radicals than reactions of alpha-tocopherol (alpha-TOH), they were significantly more reactive than alpha-TOH in phosphatidylcholine lipid bilayers - consistent with the greater potency of Fer-1 and Lip-1 relative to alpha-TOH as inhibitors of ferroptosis. None of Fer-1, Lip-1, and alpha-TOH inhibited human 15-lipoxygenase-1 (15-LOX-1) overexpressed in HEK-293 cells when assayed at concentrations where they inhibited ferroptosis. These results stand in stark contrast to those obtained with a known 15-LOX-1 inhibitor (PD146176), which was able to inhibit the enzyme at concentrations where it was effective in inhibiting ferroptosis. Given the likelihood that Fer-1 and Lip-1 subvert ferroptosis by inhibiting lipid peroxidation as RTAs, we evaluated the antiferroptotic potential of 1,8-tetrahydronaphthyridinols (hereafter THNs): rationally designed radical-trapping antioxidants of unparalleled reactivity. We show for the first time that the inherent reactivity of the THNs translates to cell culture, where lipophilic THNs were similarly effective to Fer-1 and Lip-1 at subverting ferroptosis induced by either pharmacological or genetic inhibition of the hydroperoxide-detoxifying enzyme Gpx4 in mouse fibroblasts, and glutamate-induced death of mouse hippocampal cells. These results demonstrate that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process.
Antifungal Activity of the Lipophilic Antioxidant Ferrostatin-1.[Pubmed:28783875]
Chembiochem. 2017 Oct 18;18(20):2069-2078.
Ferrostatin-1 (Fer-1) is a lipophilic antioxidant that effectively blocks ferroptosis, a distinct non-apoptotic form of cell death caused by lipid peroxidation. During many infections, both pathogens and host cells are subjected to oxidative stress, but the occurrence of ferroptosis had not been investigated. We examined ferroptosis in macrophages infected with the pathogenic yeast Histoplasma capsulatum. Unexpectedly, Fer-1 not only reduced the death of macrophages infected in vitro, but inhibited the growth of H. capsulatum and related species Paracoccidioides lutzii and Blastomyces dermatitidis at concentrations under 10 mum. Other antioxidant ferroptosis inhibitors, including liproxstatin-1, did not prevent fungal growth or reduce macrophage death. Structural analysis revealed a potential similarity of Fer-1 to inhibitors of fungal sterol synthesis, and ergosterol content of H. capsulatum decreased more than twofold after incubation with Fer-1. Strikingly, additional Fer-1 analogues with slight differences from Fer-1 had limited impact on fungal growth. In conclusion, the ferroptosis inhibitor Fer-1 has unexpected antifungal potency distinct from its antiferroptotic activity.
Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models.[Pubmed:24592866]
J Am Chem Soc. 2014 Mar 26;136(12):4551-6.
Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.
Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib.[Pubmed:23505071]
Int J Cancer. 2013 Oct 1;133(7):1732-42.
The multikinase inhibitor sorafenib is currently the treatment of reference for advanced hepatocellular carcinoma (HCC). In our report, we examined the cytotoxic effects of sorafenib on HCC cells. We report that the depletion of the intracellular iron stores achieved by using the iron chelator deferoxamine (DFX) strikingly protects HCC cells from the cytotoxic effects of sorafenib. The protective effect of the depletion of intracellular iron stores could not be explained by an interference with conventional forms of programmed cell death, such as apoptosis or autophagic cell death. We also found that DFX did not prevent sorafenib from reaching its intracellular target kinases. Instead, the depletion of intracellular iron stores prevented sorafenib from inducing oxidative stress in HCC cells. We examined the possibility that sorafenib might exert a cytotoxic effect that resembles ferroptosis, a form of cell death in which iron-dependent oxidative mechanisms play a pivotal role. In agreement with this possibility, we found that pharmacological inhibitors (ferrostatin-1) and genetic procedures (RNA interference against IREB-2) previously reported to modulate ferroptosis, readily block the cytotoxic effects of sorafenib in HCC cells. Collectively, our findings identify ferroptosis as an effective mechanism for the induction of cell death in HCC. Ferroptosis could potentially become a goal for the medical treatment of HCC, thus opening new avenues for the optimization of the use of sorafenib in these tumors.
Ferroptosis: an iron-dependent form of nonapoptotic cell death.[Pubmed:22632970]
Cell. 2012 May 25;149(5):1060-72.
Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration.