| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
FSP1 (EC50 = 103 nM)
Ferroptosis suppressor protein 1 (FSP1/AIFM2). iFSP1 is a potent, selective, and glutathione-independent inhibitor of FSP1 with an EC50 of 103 nM. FSP1 is a key negative regulator of ferroptosis that functions in parallel to glutathione peroxidase 4 (GPX4) to protect cells from lipid peroxidation. FSP1 reduces ubiquinone to ubiquinol, which acts as a lipophilic radical-trapping antioxidant that prevents lipid peroxidation. By inhibiting FSP1, iFSP1 sensitizes cells to ferroptosis, particularly in cells where GPX4 is also inhibited or deficient. FSP1 has emerged as a promising target for cancer therapy, as many cancer cells rely on FSP1 to evade ferroptosis. |
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| ln Vitro |
iFSP1 (0.001-1 μM; 24 hours) inhibits the growth of Gpx4-knockout cells in a dose-dependent manner but not the growth of wild-type cells. Ferroptosis-inducing iFSP1 can be prevented in GPX4 knockout cells by treatment with the ferroptosis inhibitor Lip-1[1].
iFSP1 (0.001-1 μM; 24 hours) is less effective than genetic deletion of FSP1, whereas iFSP1 treatment in the FSP1-knockout background had no additive effect to RSL3-induced ferroptosis[1]. iFSP1 (3 μM; 24 hours) treatment results in an obvious toxicity of RSL3 in a panel of genetically engineered (FSP1-knockout) human cancer cell lines[1]. AIFM2: A previously unrecognized anti-ferroptotic gene is the flavoprotein apoptosis-inducing factor mitochondria-associated 2. Ironoptosis suppressor protein 1 (FSP1), also known as AIFM2, is a protein.[1] iFSP1 demonstrates potent in vitro activity against FSP1 with an EC50 of 103 nM. In cell-based assays, iFSP1 selectively induces ferroptosis in GPX4-knockout cells that overexpress FSP1. The compound sensitizes various human cancer cell lines to ferroptosis inducers such as (1S,3R)-RSL3. iFSP1 is glutathione-independent, meaning that its activity is not affected by cellular glutathione levels, distinguishing it from other ferroptosis inducers that target GPX4. The compound's selectivity for FSP1 over other targets has been confirmed in selectivity profiling studies. Further detailed in vitro data are available in the primary literature. |
| ln Vivo |
In vivo activity of iFSP1 has been investigated in preclinical models of cancer. By inhibiting FSP1, iFSP1 promotes ferroptosis and may have therapeutic effects in cancers that are dependent on FSP1 for survival. However, specific in vivo data, including efficacy in animal models, pharmacokinetics, and toxicity, are not extensively detailed in the available literature summary. Further information would be available in the primary research publications.
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| Enzyme Assay |
Enzyme inhibition assays for iFSP1 are performed using recombinant FSP1 enzyme. The compound is incubated with the enzyme and a substrate, and the inhibition of FSP1 activity is measured. The EC50 of 103 nM is determined from dose-response curves. Selectivity against other targets is assessed using broad panel screening, confirming the compound's selectivity for FSP1.
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| Cell Assay |
After plating, cells are seeded on 96-well plates (2,500 cells per well) and given an iFSP-1 treatment. According to the manufacturer's instructions, cell viability is evaluated 24 h (unless otherwise specified) after treatment using AquaBluer as an indicator of viable cells.
Cell-based assays for iFSP1 are conducted using cell lines to study ferroptosis. Cells are treated with the compound at various concentrations, and the following endpoints are assessed: cell viability (by MTT or CellTiter-Glo), lipid peroxidation (by C11-BODIPY fluorescence), and ferroptosis markers. The compound's ability to induce ferroptosis is evaluated, particularly in cells with GPX4 deficiency or in the presence of ferroptosis inducers. The specificity of the observed effects can be confirmed by using cells with FSP1 knockdown or by using ferroptosis inhibitors such as ferrostatin-1. |
| Animal Protocol |
In vivo studies for iFSP1 would typically involve administration to animal models of cancer. The compound's ability to inhibit FSP1 activity in tissues can be assessed by measuring ferroptosis markers. However, specific in vivo data for iFSP1 are not extensively detailed in the available literature summary.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of iFSP1 are not extensively reported in the available literature. As a small molecule FSP1 inhibitor with a molecular weight of 323.35, the compound would be expected to have reasonable bioavailability if administered appropriately, though this would need to be confirmed experimentally. Storage recommendations include standard conditions for research compounds. The compound is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
Toxicological data for iFSP1 are not extensively reported in the available literature. The compound is intended for research use only and is not approved for clinical use. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation.
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| References | |
| Additional Infomation |
IFSP1 belongs to the pyridobenzimidazole class of compounds, with the structure pyrido[1,2-a]benzimidazole, substituted at positions 1, 2, 3, and 4 with amino, cyano, 4-methylphenyl, and cyano groups, respectively. It is a potent inhibitor of ferroptosis suppressor protein 1 (FSP1), with an EC50 of 103 nM. It induces ferroptosis in GPX4 knockout cells overexpressing FSP1. IFSP1 possesses multiple functions as a ferroptosis inducer, antitumor agent, and ferroptosis suppressor protein 1 inhibitor. It belongs to the toluene, nitrile, primary amine, aromatic amine, and pyridobenzimidazole classes of compounds.
iFSP1 is a potent, selective, and glutathione-independent inhibitor of ferroptosis suppressor protein 1 (FSP1/AIFM2) with an EC50 of 103 nM. It is a valuable tool for studying ferroptosis and its role in cancer and other diseases. The compound is not approved for clinical use and is supplied for research purposes only. Synonyms include iFSP1 (no other common synonyms identified). The compound is available from multiple chemical suppliers. |
| Molecular Formula |
C₂₀H₁₃N₅
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|---|---|
| Molecular Weight |
323.35
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| Exact Mass |
323.117
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| Elemental Analysis |
C, 74.29; H, 4.05; N, 21.66
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| CAS # |
150651-39-1
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| Related CAS # |
150651-39-1
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| PubChem CID |
699043
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.369
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
25
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| Complexity |
592
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N12C(=C(C#N)C(C3C=CC(C)=CC=3)=C(C#N)C1=NC1C=CC=CC2=1)N
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| InChi Key |
FNESYDFRCQEEKA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H13N5/c1-12-6-8-13(9-7-12)18-14(10-21)19(23)25-17-5-3-2-4-16(17)24-20(25)15(18)11-22/h2-9H,23H2,1H3
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| Chemical Name |
1-amino-3-(4-methylphenyl)pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile
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| Synonyms |
iFSP1; iFSP-1; iFSP 1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~20 mg/mL (~61.9 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (6.19 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0926 mL | 15.4631 mL | 30.9262 mL | |
| 5 mM | 0.6185 mL | 3.0926 mL | 6.1852 mL | |
| 10 mM | 0.3093 mL | 1.5463 mL | 3.0926 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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