FIN56
目录号 : GC30039
FIN56 是一种新型的铁死亡诱导剂，它通过增加 GPX4 的降解来触发铁死亡 。
Cas No.:1083162-61-1
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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| Cell experiment [1]: | |
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Cell lines |
LN229 and U118 GBM cell lines |
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Preparation Method |
Cells were plated into 96-well plates and incubated overnight. Different doses of FIN56 (0, 0.1, 0.5, 1.0, 2.0 4.0 and 8.0 µM) was added to wells. 24 h later, CCK-8 solution was added to each well. 2 h later, samples were measured at 450 nm on a microplate reader. |
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Reaction Conditions |
FIN56 (0-8.0 µM);24 h |
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Applications |
FIN56 decreased the cell viability of LN229 and U118 cells in a dose-dependent manner. |
| Animal experiment [1]: | |
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Animal models |
Nude mouse model |
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Preparation Method |
LN229 cells were injected subcutaneously into the right shoulder of 4-week-old nude mice. 2 weeks later, nude mice (n = 10) were divided into two groups, control group and FIN56 treatment group. Subcutaneous tumors were harvested 30 days after treatment. |
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Dosage form |
30 days |
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Applications |
FIN56 decreased tumor volume obviously, FIN56 significantly increased protein levels of 4-HNE. |
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References: [1]. Zhang X, Guo Y, et,al. FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021 Sep 13;12(22):6610-6619. doi: 10.7150/jca.58500. PMID: 34659551; PMCID: PMC8517990. |
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FIN56, a novel ferroptosis inducer, triggers ferroptosis by increasing the degradation of GPX4 [1,4]. FIN56 also activates squalene synthase, an enzyme involved in the cholesterol synthesis [2].
FIN56 (0-8.0 μM;24 h) decreased the cell viability of LN229 and U118 cells in a dose-dependent manner. After FIN56 treatment, cell cycle of LN229 and U118 was arrested at GO/G1 phases [3]. FIN56 (1-5 μM;3-24 h) induces autophagy-associated cell death in Bladder cancer (BC) cells[4]. Inhibition of Gpx4 by FIN56 (0-20μM) abolished the protective effects of NAC on HG-induced ferroptosis[5]. the protein expression of salusin β was upregulated by ferroptosis activators, such as FIN56. Pretreatment with ferrostatin 1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin β in HK 2 cells exposed to HG[6]. AS-IV markedly accelerated proliferation, suppressed apoptosis, and reduced ROS and LDH accumulation. The effects of AS-IV on SCI were inhibited by si-TFEB, and this inhibition was further reinforced by the addition of FIN56(5 μM)[7].
FIN56 (30days) decreased tumor volume obviously, FIN56 significantly increased protein levels of 4-HNE[3].
References:
[1]. Shimada K, Skouta R, et,al. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol. 2016 Jul;12(7):497-503. doi: 10.1038/nchembio.2079. Epub 2016 May 9. PMID: 27159577; PMCID: PMC4920070.
[2]. Gaschler MM, Andia AA, et,al.FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol. 2018 May;14(5):507-515. doi: 10.1038/s41589-018-0031-6. Epub 2018 Apr 2. PMID: 29610484; PMCID: PMC5899674.
[3]. Zhang X, Guo Y, et,al. FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021 Sep 13;12(22):6610-6619. doi: 10.7150/jca.58500. PMID: 34659551; PMCID: PMC8517990.
[4]. Lei P, Bai T, et,al.Mechanisms of Ferroptosis and Relations With Regulated Cell Death: A Review. Front Physiol. 2019 Feb 26;10:139. doi: 10.3389/fphys.2019.00139. PMID: 30863316; PMCID: PMC6399426.
[5]. Li Q, Liao J,et,al. NAC alleviative ferroptosis in diabetic nephropathy via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2/Gpx4 pathway. Free Radic Biol Med. 2022 Jul;187:158-170. doi: 10.1016/j.freeradbiomed.2022.05.024. Epub 2022 May 31. Erratum in: Free Radic Biol Med. 2022 Aug 20;189:1. PMID: 35660452.
[6].Wang WJ, Jiang X,et,al.Salusin?β participates in high glucose?induced HK?2 cell ferroptosis in a Nrf?2?dependent manner. Mol Med Rep. 2021 Sep;24(3):674. doi: 10.3892/mmr.2021.12313. Epub 2021 Jul 23. PMID: 34296310; PMCID: PMC8335735.
[7]. Zhou Y, Li L, et,al.Astragaloside IV ameliorates spinal cord injury through controlling ferroptosis in H2O2-damaged PC12 cells in vitro. Ann Transl Med. 2022 Nov;10(21):1176. doi: 10.21037/atm-22-5196. PMID: 36467371; PMCID: PMC9708485.
FIN56 是一种新型的铁死亡诱导剂，它通过增加 GPX4 的降解来触发铁死亡 [1,4]。 FIN56 还激活角鲨烯合酶，一种参与胆固醇合成的酶[2]。
FIN56（0-8.0 μM；24 小时）以剂量依赖性方式降低 LN229 和 U118 细胞的细胞活力。 FIN56处理后，LN229和U118的细胞周期停滞在GO/G1期[3]。 FIN56（1-5 μM；3-24 小时）在膀胱癌 (BC) 细胞中诱导自噬相关细胞死亡[4]。 FIN56 (0-20μM) 对 Gpx4 的抑制作用消除了 NAC 对 HG 诱导的铁死亡的保护作用[5]。 salusin β 的蛋白表达被 FIN56 等铁死亡激活剂上调。用 ferrostatin 1（一种铁死亡抑制剂）预处理可防止暴露于 HG[6] 的 HK 2 细胞中 salusin β 的蛋白表达上调。 AS-IV 显着加速增殖，抑制细胞凋亡，并减少 ROS 和 LDH 积累。 AS-IV 对 SCI 的影响被 si-TFEB 抑制，并且这种抑制通过添加 FIN56(5 μM)[7] 得到进一步加强。
FIN56（30天）明显缩小肿瘤体积，FIN56显着增加4-HNE蛋白水平[3]。
| Cas No. | 1083162-61-1 | SDF | |
| Canonical SMILES | O=S(C1=CC(/C2=N\O)=C(C3=C2C=C(S(=O)(NC4CCCCC4)=O)C=C3)C=C1)(NC5CCCCC5)=O | ||
| 分子式 | C25H31N3O5S2 | 分子量 | 517.66 |
| 溶解度 | DMSO : ≥ 100 mg/mL (193.18 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.9318 mL | 9.6588 mL | 19.3177 mL |
| 5 mM | 0.3864 mL | 1.9318 mL | 3.8635 mL |
| 10 mM | 0.1932 mL | 0.9659 mL | 1.9318 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells
Cell Death Dis 2021 Oct 29;12(11):1028.34716292 PMC8556316
Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines of evidence suggest that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms remain unclear. FIN56, a type 3 ferroptosis inducer, triggers ferroptosis by promoting glutathione peroxidase 4 (GPX4) protein degradation via a not fully understood pathway. Here, we determined that FIN56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery. Furthermore, we found that autophagy inhibition at different stages attenuates Fin56-induced oxidative stress and GPX4 degradation. Moreover, we investigated the effects of FIN56 in combination with Torin 2, a potent mTOR inhibitor used to activate autophagy, on cell viability. We found that FIN56 synergizes with Torin 2 in cytotoxicity against bladder cancer cells. Collectively, our findings not only support the concept that ferroptosis is a type of autophagy-dependent cell death but imply that the combined application of ferroptosis inducers and mTOR inhibitors is a promising approach to improve therapeutic options in the treatment of bladder cancer.
Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus
J Diabetes Res 2021 Jun 28;2021:9999612.34258295 PMC8257355
Ferroptosis is a novel form of nonapoptotic regulated cell death (RCD). It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes, especially glutathione peroxidase 4 (GPX4). RAS-selective lethal 3 (RSL3), erastin, and ferroptosis inducing 56 (FIN56) induce ferroptosis via different manners targeting GPX4 function. Acyl-CoA synthetase long-chain family 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and lipoxygenases (LOXs) participate in the production of lipid peroxides. Heat shock protein family B member 1 (HSPB1) and nuclear receptor coactivator 4 (NCOA4) regulate iron homeostasis preventing ferroptosis caused by the high concentration of intracellular iron. Ferroptosis is ubiquitous in our body as it exists in both physiologic and pathogenic processes. It is involved in glucose-stimulated insulin secretion (GSIS) impairment and arsenic-induced pancreatic damage in the pathogenesis of diabetes. Moreover, iron and the iron-sulfur (Fe-S) cluster influence each other, causing mitochondrial iron accumulation, more reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, failure in biosynthesis of insulin, and ferroptosis in β-cells. In addition, ferroptosis also engages in the pathogenesis of diabetic complications such as myocardial ischemia and diabetic cardiomyopathy (DCM). In this review, we summarize the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM).
The release and activity of HMGB1 in ferroptosis
Biochem Biophys Res Commun 2019 Mar 5;510(2):278-283.30686534 10.1016/j.bbrc.2019.01.090
Damage-associated molecular pattern molecules (DAMPs) are endogenous danger signals that alert the innate immune system and shape the inflammation response to cell death. However, the release and activity of DAMPs in ferroptosis, a recently identified form of regulated necrosis characterized by iron overload and lipid peroxidation, still remain poorly understood. Here, we demonstrate that HMGB1 is a DAMP released by ferroptotic cells in an autophagy-dependent manner. Both type I and II ferroptosis activators, including erastin, sorafenib, RSL3, and FIN56, induce HMGB1 release in cancer and noncancer cells. In contrast, genetic ablation (using ATG5-/- or ATG7-/- cells) or pharmacologic inhibition (the administration of bafilomycin A1 or chloroquine) of autophagy was found to block ferroptosis activator-induced HMGB1 release. Mechanically, autophagy-mediated HDAC inhibition promotes HMGB1 acetylation, resulting in HMGB1 release in ferroptosis. Moreover, AGER, but not TLR4, is required for HMGB1-mediated inflammation in macrophages in response to ferroptotic cells. These studies suggest that HMGB1 inhibition might have some potential therapeutic effects in ferroptosis-associated human disease.
AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System Xc- Activity
Curr Biol 2018 Aug 6;28(15):2388-2399.e5.30057310 PMC6081251
Ferroptosis is a form of regulated cell death triggered by lipid peroxidation after inhibition of the cystine/glutamate antiporter system Xc-. However, key regulators of system Xc- activity in ferroptosis remain undefined. Here, we show that BECN1 plays a hitherto unsuspected role in promoting ferroptosis through directly blocking system Xc- activity via binding to its core component, SLC7A11 (solute carrier family 7 member 11). Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system Xc- inhibitors (e.g., erastin, sulfasalazine, and sorafenib), but not other ferroptosis inducers including RSL3, FIN56, and buthionine sulfoximine. Mechanistically, AMP-activated protein kinase (AMPK)-mediated phosphorylation of BECN1 at Ser90/93/96 is required for BECN1-SLC7A11 complex formation and lipid peroxidation. Inhibition of PRKAA/AMPKα by siRNA or compound C diminishes erastin-induced BECN1 phosphorylation at S93/96, BECN1-SLC7A11 complex formation, and subsequent ferroptosis. Accordingly, a BECN1 phosphorylation-defective mutant (S90,93,96A) reverses BECN1-induced lipid peroxidation and ferroptosis. Importantly, genetic and pharmacological activation of the BECN1 pathway by overexpression of the protein in tumor cells or by administration of the BECN1 activator peptide Tat-beclin 1, respectively, increases ferroptotic cancer cell death (but not apoptosis and necroptosis) in vitro and in vivo in subcutaneous and orthotopic tumor mouse models. Collectively, our work reveals that BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis.
FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma
J Cancer 2021 Sep 13;12(22):6610-6619.34659551 PMC8517990
Objective: To explore the anti-tumor effect of FIN56, a novel ferroptosis inducer, on glioblastoma and its underlying mechanisms. Methods: Two human glioblastoma cell lines, LN229 and U118 were applied in this study. Anti-tumor effect was measured by CCK-8 assay, EdU assay and cell cycle analysis. Fluorescent probes, immunofluorescence, plasmid transfection, shRNA knocking out, reverse transcription PCR, western blot analysis, and transmission electron microscopy were used to study the underlying mechanisms. At last, a subcutaneous nude mice model was used to study the anti-tumor effect of FIN56 in vivo. The GraphPad Prism software program was applied for statistical analysis. Results: FIN56 decreased cell viability, inhibited cell proliferation and caused cell cycle arrest on LN229 and U118 cells. Further study showed that FIN56 induced ferroptosis and induced lysosomal membrane permeabilization in a ferroptosis and transfactor EB dependent manner. Animal study demonstrated that FIN56 inhibited glioma growth and caused ferroptosis in vivo. Conclusion: FIN56 is a promising anti-tumor compound.