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iFSP1

Catalog No.GC45928 Copy One-Click Copy Product Info

iFSP1 is a potent glutathione-independent ferroptosis suppressor protein 1 (FSP1) inhibitor , which has an EC50 value of 103nM.

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iFSP1 Chemical Structure

Cas No.: 150651-39-1

Size Price Stock Qty
10mM (in 1mL DMSO)
$37.00
In stock
5mg
$21.00
In stock
10mg
$34.00
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50mg
$149.00
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100mg
$280.00
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Sample solution is provided at 25 µL, 10mM.



Description of iFSP1

iFSP1 is a potent glutathione-independent ferroptosis suppressor protein 1 (FSP1) inhibitor , which has an EC50 value of 103nM[1]. iFSP1 inhibits ferroptosis by catalyzing the production of antioxidant CoQH2 [2].

iFSP1 ( 6μM , 24h ) will restore cancer cell sensitivity to ferroptosis[3] . iFSP1 ( 3μM , 3h ) only exerts its function on hFSP1 but not mFSP1[4]. iFSP1 ( 3μM , 24h ) combined with CD36 overexpression induces the increasing synthesis of ferroptosis marker ACSL4 in Transformed C3H Mouse Kidney-1 (TCMK-1) cells upon the treatment of cisplatin[5].

iFSP1 ( 10mg/kg/day ; 4 weeks ; intraperitoneal injection ) potently induced ferroptosis, which promoted innate and adaptive antitumor immune responses and effectively suppressed Hepatocellular carcinoma ( HCC ) tumor growth[6]. iFSP1 (2mg/kg/day ; 2 weeks ; intraperitoneal injection ) and olaparib combined treatment strongly inhibited tumour proliferation in breast cancer susceptibility gene ( BRCA )-proficient ovarian cancer cell lines , patient-derived organoids ( PDOs ) and xenograft mouse models[7].

References:

[1] DOLL S, FREITAS F P, SHAH R, et al. FSP1 is a glutathione-independent ferroptosis suppressor [J]. Nature, 2019, 575(7784): 693-8.
[2] TAO H, DAR H Y, TIAN C, et al. Differences in hepatocellular iron metabolism underlie sexual dimorphism in hepatocyte ferroptosis [J]. Redox Biol, 2023, 67(102892.
[3] PANCZYSZYN E, SAVERIO V, MONZANI R, et al. FSP1 is a predictive biomarker of osteosarcoma cells' susceptibility to ferroptotic cell death and a potential therapeutic target [J]. Cell Death Discov, 2024, 10(1): 87.
[4] XAVIER DA SILVA T N, SCHULTE C, ALVES A N, et al. Molecular characterization of AIFM2/FSP1 inhibition by iFSP1-like molecules [J]. Cell Death Dis, 2023, 14(4): 281.
[5] MA Y, HUANG L, ZHANG Z, et al. CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury [J]. Genes Dis, 2024, 11(1): 449-63.
[6] CHEU J W, LEE D, LI Q, et al. Ferroptosis Suppressor Protein 1 Inhibition Promotes Tumor Ferroptosis and Anti-tumor Immune Responses in Liver Cancer [J]. Cell Mol Gastroenterol Hepatol, 2023, 16(1): 133-59.
[7] MIAO H, MENG H, ZHANG Y, et al. FSP1 inhibition enhances olaparib sensitivity in BRCA-proficient ovarian cancer patients via a nonferroptosis mechanism [J]. Cell Death Differ, 2024, 31(4): 497-510.

Protocol of iFSP1

Cell experiment [1]:

Cell lines

4-hydroxytamoxifen (TAM)-inducible Gpx4−/− murine immortalized fibroblasts ( Pfa1 )

Preparation Method

These cells harbor two loxP-flanked Gpx4 alleles and stably express TAM inducible Cre recombinase allowing the genetic deletion of Gpx4 at will. For all experiments using Gpx4−/− the well were treated with 4-hydroxitamoxifen (TAM) 1μM. All cells were cultured with were cultured in DMEM-high glucose ( 4.5g glucose/L ) with 10% fetal bovine serum (FBS) , Glutamax , and 1% penicillin/ streptomycin at 37℃ with 5% CO2 and verified tobe negative for mycoplasma. The cells were treated with 3μM iFSP1 within 3h .

Reaction Conditions

3μM , 3h 

Applications

iFSP1 is a potent inhibitor of FSP1.

Animal experiment [2]:

Animal models

Male C57BL/6N mice

Preparation Method

For hydrodynamic tail vein injection (HDTVi) model , fatty livers were induced by replacing standard diets with HFD 24 hoursprior to HDTVi and for the duration of the experiment. FSP1 was inhibited in vivo by daily intraperitoneal injections of 10 mg/kg iFSP1 . To study the effect of iFSP1 on tumor immune infiltrates, HDTVi-induced tumors were harvested 4 weeks post HDTVi for dissociation and histological analysis.

Dosage form

10mg/kg ; 4 weeks ; intraperitoneal injection.

Applications

iFSP1 potently induced ferroptosis , which promoted innate and adaptive antitumor immune responses and effectively suppressed Hepatocellular carcinoma (HCC) tumor growth.

References:

[1] XAVIER DA SILVA T N, SCHULTE C, ALVES A N, et al. Molecular characterization of AIFM2/FSP1 inhibition by iFSP1-like molecules [J]. Cell Death Dis, 2023, 14(4): 281.
[2] CHEU J W, LEE D, LI Q, et al. Ferroptosis Suppressor Protein 1 Inhibition Promotes Tumor Ferroptosis and Anti-tumor Immune Responses in Liver Cancer [J]. Cell Mol Gastroenterol Hepatol, 2023, 16(1): 133-59.

Chemical Properties of iFSP1

Cas No. 150651-39-1 SDF
Chemical Name 1-amino-3-(4-methylphenyl)-pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile
Canonical SMILES NC1=C(C#N)C(C2=CC=C(C)C=C2)=C(C#N)C3=NC4=CC=CC=C4N31
Formula C20H13N5 M.Wt 323.4
Solubility 1mg/mL in ethanol, 25mg/mL in DMSO, 30mg/mL in DMF Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of iFSP1

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 3.0921 mL 15.4607 mL 30.9215 mL
5 mM 618.4 μL 3.0921 mL 6.1843 mL
10 mM 309.2 μL 1.5461 mL 3.0921 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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3. All of the above co-solvents are available for purchase on the GlpBio website.

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Review for iFSP1

Average Rating: 5 ★★★★★ (Based on Reviews and 34 reference(s) in Google Scholar.)

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