| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
FSEN1 targets ferroptosis suppressor protein 1 (FSP1), also known as AIFM2. FSP1 is a key regulator of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. FSEN1 is a noncompetitive (uncompetitive) inhibitor of FSP1 that is selective for FSP1 over NQO1. By inhibiting FSP1, FSEN1 sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors and endoperoxide-containing ferroptosis inducers.
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| ln Vitro |
FSEN1 (0–15 µM; H460C Cas9 cells) inhibits FSP1 to make cancer cells more susceptible to ferroptosis and is synthetically deadly to GPX4 inhibitors [1].
In vitro, FSEN1 (0-15 µM; H460C Cas9 cells) inhibits FSP1 to make cancer cells more susceptible to ferroptosis. FSEN1 is synthetic lethal with GPX4 inhibitors. The compound sensitizes H460 lung cancer cells to lipid peroxidation and ferroptosis induced by GPX4 inhibition. Dose-response analyses show that FSEN1 inhibits FSP1 activity and induces ferroptosis in H460C GPX4KO cells. The compound's effects are blocked by ferroptosis inhibitors such as Fer-1, DFO, idebenone, and tocopherol. |
| ln Vivo |
In vivo data for FSEN1 is limited in publicly available sources. As a potent FSP1 inhibitor that triggers ferroptosis in cancer cells, FSEN1 has potential applications in animal models of cancer, particularly in combination with GPX4 inhibitors. By sensitizing cancer cells to ferroptosis, FSEN1 could enhance the efficacy of existing ferroptosis-inducing therapies. However, specific published in vivo efficacy studies are not widely reported. FSEN1 is primarily used as a research tool for studying ferroptosis mechanisms.
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| Enzyme Assay |
The in vitro FSP1 inhibition assay for FSEN1 uses recombinant FSP1 enzyme and a suitable substrate. Enzyme activity is measured using absorbance-based or fluorescence-based detection methods, and IC₅₀ values are calculated from dose-response curves. Selectivity profiling against NQO1 is performed using similar assay formats. Ferroptosis induction is assessed in H460C cells or H460C GPX4KO cells by measuring cell viability using standard assays such as CellTiter-Glo. The synthetic lethal relationship with GPX4 inhibitors is confirmed by combination studies.
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| Cell Assay |
Cellular assays for FSEN1 are conducted in H460C Cas9 lung cancer cells and H460C GPX4KO cells. Cells are treated with FSEN1 at concentrations of 0-15 µM. Cell viability is measured using standard assays such as CellTiter-Glo. Ferroptosis is confirmed by using ferroptosis inhibitors such as Fer-1 (2 μM), DFO (100 μM), idebenone (10 μM), and tocopherol (10 μM). Apoptosis inhibitors (Z-VAD, 10 μM) and necroptosis inhibitors (Nec1s, 1 μM) are used as controls to confirm ferroptosis specificity. Lipid peroxidation is measured using appropriate fluorescent probes.
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| Animal Protocol |
In vivo studies for FSEN1 would typically involve xenograft mouse models of cancer, particularly lung cancer or other malignancies where ferroptosis induction is therapeutic. The compound would be administered via intraperitoneal or oral routes at doses determined by pharmacokinetic studies. Efficacy would be assessed by measuring tumor growth inhibition, with pharmacodynamic markers such as lipid peroxidation and ferroptosis markers evaluated in tumor tissues. However, specific published in vivo protocols for FSEN1 are not available in the current literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for FSEN1 is not extensively reported in publicly available sources. The compound has a molecular weight of 484.41 g/mol and a molecular formula of C₂₂H₂₂BrN₅OS. It has a logP of 5.1. The compound is soluble in DMF at ≥1 mg/mL. Storage conditions: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Detailed PK parameters such as half-life and bioavailability are not available in the current literature for this research compound.
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| Toxicity/Toxicokinetics |
Toxicity data for FSEN1 is limited in publicly available sources. As with all research compounds, FSEN1 is intended for research use only and not for human therapeutic applications. The compound's selectivity for FSP1 over NQO1 suggests a favorable off-target profile. Standard in vitro cytotoxicity assays in normal cell lines and in vivo tolerability studies would be required for a complete toxicity assessment. No specific toxicity data has been reported in the available literature.
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| References | |
| Additional Infomation |
FSEN1 is a potent, noncompetitive inhibitor of ferroptosis suppressor protein 1 (FSP1) with an IC₅₀ of 313 nM. It is selective for FSP1 over NQO1 (IC₅₀ >100 μM). FSEN1 triggers ferroptosis in cancer cells by inhibiting FSP1 and is synthetic lethal with GPX4 inhibitors. In H460C cells, FSEN1 (0-15 µM) sensitizes cancer cells to ferroptosis. The compound has a molecular formula of C₂₂H₂₂BrN₅OS and a molecular weight of 484.41 g/mol. FSEN1 is a valuable research tool for studying ferroptosis mechanisms and cancer therapeutics.
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| Molecular Formula |
C22H22BRN5OS
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|---|---|
| Molecular Weight |
484.411982059479
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| Exact Mass |
483.072
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| CAS # |
862808-01-3
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| PubChem CID |
22583648
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
550
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C=CC(=CC=1)C1=NN=C2N1C=C(CN1CCN(C3C=CC(=CC=3)OC)CC1)S2
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| InChi Key |
JGXIXBKKDUNARN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H22BrN5OS/c1-29-19-8-6-18(7-9-19)27-12-10-26(11-13-27)14-20-15-28-21(24-25-22(28)30-20)16-2-4-17(23)5-3-16/h2-9,15H,10-14H2,1H3
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| Chemical Name |
3-(4-bromophenyl)-6-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-[1,3]thiazolo[2,3-c][1,2,4]triazole
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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) |
DMF :≥ 1 mg/mL (~2.06 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0644 mL | 10.3218 mL | 20.6437 mL | |
| 5 mM | 0.4129 mL | 2.0644 mL | 4.1287 mL | |
| 10 mM | 0.2064 mL | 1.0322 mL | 2.0644 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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