Fatostatin A hydrobromide
(Synonyms: Fatostatin (125B11) HBr) 目录号 : GC18121
Fatostatin A hydrobromide是一种能够特异性抑制甾醇调节元件结合蛋白（SREBP）活性的化合物，可有效抑制SREBP-1和SREBP-2的激活过程。
Cas No.:298197-04-3
Sample solution is provided at 25 µL, 10mM.
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Fatostatin A hydrobromide is a compound that specifically inhibits the activity of sterol regulatory element-binding proteins (SREBPs), effectively suppressing the activation of SREBP-1 and SREBP-2[1]. By binding to the SREBP cleavage-activating protein (SCAP), Fatostatin A hydrobromide inhibits the transport of SREBPs from the endoplasmic reticulum to the Golgi apparatus, ultimately reducing the transcriptional level of intracellular lipogenesis-related genes[2]. Fatostatin A hydrobromide also regulates glucose and lipid metabolism and suppresses cancer progression[3-4].
In vitro, treatment of cancer cells (such as HeLa, U87, and SH-SY5Y) with Fatostatin A hydrobromide (2.11–5μM) for 24–48 hours inhibits SREBP maturation and induces G₂/M phase arrest. Concurrently, Fatostatin A hydrobromide disrupts mitotic spindle assembly by inhibiting tubulin polymerization, activates the spindle assembly checkpoint, and ultimately leads to multipolar division and caspase 3/7-dependent cell death[5]. Pretreatment of pancreatic cancer cells (BxPC-3, MIAPaCa-2) with Fatostatin A hydrobromide (10–30μM) for 24–72 hours significantly suppresses cell proliferation and clonogenic ability while reducing intracellular lipid synthesis. Furthermore, Fatostatin A hydrobromide induces iron accumulation, increases reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and downregulates GPX4 expression, triggering ferroptosis[6].
In vivo, Fatostatin A hydrobromide (25mg/kg) administered via tail vein injection in a 6-week-old BALB/c nude mouse model of intracranial glioblastoma (three times per week for 4 weeks) significantly inhibits tumor growth and prolongs survival[7]. Fatostatin A hydrobromide (25mg/kg; injected three times a week for 4 weeks) was administered intraperitoneally to 4-week-old BALB/c nude mice to establish a xenograft model of endometrial cancer. Fatostatin A hydrobromide significantly inhibited tumor growth and enhanced sensitivity to progesterone therapy[8].
References:
[1] Xue L, Qi H, Zhang H, et al. Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy. Front Oncol. 2020 Aug 21;10:1510.
[2] Soyal SM, Nofziger C, Dossena S, et al. Targeting SREBPs for treatment of the metabolic syndrome. Trends Pharmacol Sci. 2015 Jun;36(6):406-16.
[3] Li M, Lu Q, Zhu Y, et al. Fatostatin inhibits SREBP2-mediated cholesterol uptake via LDLR against selective estrogen receptor α modulator-induced hepatic lipid accumulation. Chem Biol Interact. 2022 Sep 25;365:110091.
[4] Yao L, Chen S, Li W. Fatostatin inhibits the development of endometrial carcinoma in endometrial carcinoma cells and a xenograft model by targeting lipid metabolism. Arch Biochem Biophys. 2020 May 15;684:108327.
[5] Gholkar AA, Cheung K, Williams KJ, et al. Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division. J Biol Chem. 2016 Aug 12;291(33):17001-8.
[6] Cao R, Feng Z, Mo J, et al. Pharmacological inhibition of SREBP1 suppresses pancreatic cancer growth via inducing GPX4-mediated ferroptosis. Cell Signal. 2024 Dec;124:111381.
[7] Cai J, Ye Z, Hu Y, et al. Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. Cell Death Dis. 2023 Mar 25;14(3):211.
[8] Ma X, Zhao T, Yan H, et al. Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma. Cell Death Dis. 2021 May 26;12(6):544.
Fatostatin A hydrobromide是一种能够特异性抑制甾醇调节元件结合蛋白（SREBP）活性的化合物，可有效抑制SREBP-1和SREBP-2的激活过程[1]。Fatostatin A hydrobromide 通过结合SREBP裂解激活蛋白（SCAP），进而抑制SREBPs从内质网到高尔基体的转运，最终降低细胞内脂肪生成相关基因的转录水平[2]。Fatostatin A hydrobromide可调节糖脂代谢和抑制癌症发展[3-4]。
在体外，Fatostatin A hydrobromide（2.11–5μM）处理癌细胞（HeLa、U87、SH-SY5Y等）24–48小时，Fatostatin A hydrobromide可抑制SREBP成熟并诱导G₂/M期阻滞，同时通过抑制微管蛋白聚合破坏有丝分裂纺锤体组装，激活纺锤体组装检查点，最终导致多极分裂和caspase 3/7依赖的细胞死亡[5]。Fatostatin A hydrobromide（10–30μM）预处理胰腺癌细胞（BxPC-3、MIAPaCa-2）24–72小时，显著抑制细胞增殖和克隆形成能力，同时降低细胞内脂质合成；进一步通过诱导铁积累、活性氧（ROS）及丙二醛（MDA）水平升高，并下调GPX4表达，触发铁死亡[6]。
在体内，Fatostatin A hydrobromide（25mg/kg）通过尾静脉注射，用于处理6周龄BALB/c裸鼠建立的颅内胶质母细胞瘤模型（每周3次，持续4周）。Fatostatin A hydrobromide显著抑制了肿瘤生长并延长了小鼠生存期[7]。Fatostatin A hydrobromide（25mg/kg；每周注射3次，持续4周）腹腔注射处理4周龄BALB/c裸鼠建立的子宫内膜癌异种移植模型。Fatostatin A hydrobromide显著抑制了肿瘤生长并增强了孕激素治疗的敏感性[8]。
| Cell experiment [1]: | |
Cell lines | HeLa cells (human cervical carcinoma cell line), U87 and T98G (glioblastoma cell lines), MDA-MB-453 (breast cancer cell line), Jurkat T-cells (human T-cell leukemia line) |
Preparation Method | Cells were maintained in DMEM/F12, Iscove’s modified Dulbecco’s medium, or RPMI 1640 supplemented with 10% fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with Fatostatin A hydrobromide at concentrations of 2.11–5μM for 20–48 hours. |
Reaction Conditions | 2.11-5μM; 20-48h |
Applications | Fatostatin A hydrobromide induced G₂/M phase arrest in cancer cells, disrupted mitotic spindle assembly, and triggered multipolar spindle formation. Fatostatin A hydrobromide inhibited tubulin polymerization, activated the spindle assembly checkpoint, and promoted caspase-3/7-dependent mitotic catastrophe, leading to reduced cell viability. Fatostatin also suppressed SREBP target gene expression (FASN, HMGCS1) independent of its antimitotic effects. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice (female, 4-5 weeks old) |
Preparation Method | Mice were subcutaneously inoculated with IshikawaMR (IshMR) endometrial carcinoma cells (1×10⁷cells/mouse). When tumor diameter reached 5mm, mice were intraperitoneally administered Fatostatin A hydrobromide (25mg/kg) three times per week, either alone or in combination with Medroxyprogesterone acetate (MPA; 100mg/kg every two days) for 4 weeks. Tumor volume and body weight were monitored every two days. |
Dosage form | 25mg/kg; i.p.; three times per week for 4 weeks |
Applications | Fatostatin A hydrobromide significantly suppressed tumor growth in IshMR xenograft models and enhanced the sensitivity of endometrial cancer to progesterone therapy. Combined treatment with Fatostatin A hydrobromide and MPA synergistically reduced tumor volume, downregulated SREBP1 and Ki-67 expression, and increased cleaved-caspase-3 levels, indicating reversal of progesterone resistance and induction of apoptosis. |
References: | |
| Cas No. | 298197-04-3 | SDF | |
| 别名 | Fatostatin (125B11) HBr | ||
| 化学名 | 2-(2-propylpyridin-4-yl)-4-(p-tolyl)thiazole hydrobromide | ||
| Canonical SMILES | CCCC1=NC=CC(C2=NC(C3=CC=C(C=C3)C)=CS2)=C1.Br | ||
| 分子式 | C18H18N2S.HBr | 分子量 | 375.33 |
| 溶解度 | ≥ 19.76 mg/mL in DMSO, ≥ 5.02 mg/mL in EtOH | 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 | 2.6643 mL | 13.3216 mL | 26.6432 mL |
| 5 mM | 532.9 μL | 2.6643 mL | 5.3286 mL |
| 10 mM | 266.4 μL | 1.3322 mL | 2.6643 mL |
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| 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 |
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| % 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，
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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
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- Purity: >99.50%
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