iFSP1 is a novel and glutathione-independent inhibitor of ferroptosis suppressor protein 1 (FSP1) (AIFM2) with an EC50 of 103 nM. Moreover, it is a ferroptosis inducer.
Physicochemical Properties
| Molecular Formula | C₂₀H₁₃N₅ |
| Molecular Weight | 323.35 |
| Exact Mass | 323.117 |
| Elemental Analysis | C, 74.29; H, 4.05; N, 21.66 |
| CAS # | 150651-39-1 |
| Related CAS # | 150651-39-1 |
| PubChem CID | 699043 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.369 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 25 |
| Complexity | 592 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N12C(=C(C#N)C(C3C=CC(C)=CC=3)=C(C#N)C1=NC1C=CC=CC2=1)N |
| InChi Key | FNESYDFRCQEEKA-UHFFFAOYSA-N |
| 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 |
| Chemical Name | 1-amino-3-(4-methylphenyl)pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile |
| Synonyms | iFSP1; iFSP-1; iFSP 1 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | FSP1 (EC50 = 103 nM) |
| 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] |
| 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. |
| References |
[1]. FSP1 is a glutathione-independent ferroptosis suppressor.Nature. 2019 Nov;575(7784):693-698. |
| Additional Infomation | IFSP1 is a member of the class of pyridobenzimidazoles that is pyrido[1,2-a]benzimidazole substituted by amino, cyano, 4-methylphenyl, and cyano groups at positions 1, 2, 3 and 4, respectively. It is a potent inhibitor of ferroptosis suppressor protein 1 (FSP1) with EC50 of 103 nM. It induces ferroptosis in GPX4 knockout cells that overexpress FSP1. It has a role as a ferroptosis inducer, an antineoplastic agent and a ferroptosis suppressor protein 1 inhibitor. It is a member of toluenes, a nitrile, a primary amino compound, an aromatic amine and a pyridobenzimidazole. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~20 mg/mL (~61.9 mM) |
| 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 |