iFSP1
目录号 : GC45928
iFSP1是一种有效的不依赖谷胱甘肽的铁死亡抑制蛋白1（FSP1）抑制剂，其EC50值为103nM。
Cas No.:150651-39-1
Sample solution is provided at 25 µL, 10mM.
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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.
iFSP1是一种有效的不依赖谷胱甘肽的铁死亡抑制蛋白1（FSP1）抑制剂，其EC50值为103nM[1]。iFSP1通过催化抗氧化剂CoQH2的产生抑制铁死亡[2]。
iFSP1（6μM，24h）可恢复癌细胞对铁死亡的敏感性[3]。iFSP1 （3μM，3h）只对hFSP1起作用，对mFSP1不起作用[4]。iFSP1 （3μM，24h）联合CD36过表达诱导转化的小鼠肾小管上皮细胞系（TCMK-1）细胞中铁死亡标志物ACSL4的合成增加[5]。
iFSP1(10毫克/公斤/天；4周；腹腔注射)能诱导铁死亡，促进先天和适应性抗肿瘤免疫反应，有效抑制肝细胞（HCC）肿瘤生长[6]。iFSP1 (2毫克/公斤/天；2周；腹腔注射)和奥拉帕利（olaparib）联合治疗在具有乳腺癌易感基因（BRCA）功能的卵巢癌细胞系、患者来源的类器官（PDOs）和异种移植小鼠模型中显著抑制了肿瘤的增殖[7]。
| Cell experiment [1]: | |
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Cell lines |
4-hydroxytamoxifen (TAM)-inducible Gpx4−/− murine immortalized fibroblasts ( Pfa1 ) |
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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 . |
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Reaction Conditions |
3μM , 3h |
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Applications |
iFSP1 is a potent inhibitor of FSP1. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6N mice |
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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. |
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Dosage form |
10mg/kg ; 4 weeks ; intraperitoneal injection. |
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Applications |
iFSP1 potently induced ferroptosis , which promoted innate and adaptive antitumor immune responses and effectively suppressed Hepatocellular carcinoma (HCC) tumor growth. |
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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. |
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| Cas No. | 150651-39-1 | SDF | |
| 化学名 | 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 | ||
| 分子式 | C20H13N5 | 分子量 | 323.4 |
| 溶解度 | 1mg/mL in ethanol, 25mg/mL in DMSO, 30mg/mL in DMF | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0921 mL | 15.4607 mL | 30.9215 mL |
| 5 mM | 0.6184 mL | 3.0921 mL | 6.1843 mL |
| 10 mM | 0.3092 mL | 1.5461 mL | 3.0921 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet