Selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme in cholesterol biosynthesis).

羟甲基戊二酰辅酶 A 还原酶 (HMGCR) 在胆固醇生物合成中催化 HMG-CoA 限速转化为甲羟戊酸，可被氟伐他汀钠 (XU 62320) 竞争性抑制。对 HCC（人肝细胞癌细胞）的研究表明，氟伐他汀会导致 G2/M 期阻滞。当氟伐他汀 (XU 62320) 存在时，HCC 细胞显示较少的 Bcl-2 和 procaspase-9，而显示更多的 Bax、裂解的 caspase-3 和细胞色素 c。抗血脂药物氟伐他汀 (XU 62320) 可降低血浆胆固醇水平并预防心血管疾病。

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保护血管平滑肌细胞（VSMC）抗氧化应激（Nrf2通路介导）：
- 在大鼠胸主动脉VSMC中，氟伐他汀钠（Fluvastatin Sodium） （1 μM、5 μM、10 μM）预处理24小时，浓度依赖性缓解H2O2（200 μM）诱导的氧化损伤：
- 活性氧（ROS）：10 μM 氟伐他汀钠 使H2O2诱导的ROS升高降低60%（DCFH-DA荧光法）[1]
- 抗氧化酶：5 μM和10 μM 氟伐他汀钠 分别使血红素氧合酶-1（HO-1）蛋白水平升高1.8倍和2.5倍，NAD(P)H醌脱氢酶1（NQO1）升高1.5倍和2.1倍（Western blot）[1]
- Nrf2激活：10 μM 氟伐他汀钠 使Nrf2核转位率从15%升至65%（免疫荧光染色），核内Nrf2蛋白增加2.3倍（核提取物Western blot）[1]
- 诱导人肝癌细胞凋亡（线粒体途径介导）：
- 在HepG2和SMMC-7721肝癌细胞中，氟伐他汀钠（Fluvastatin Sodium） （2.5~40 μM）浓度依赖性抑制增殖并诱导凋亡：
- 抗增殖活性：HepG2细胞IC50=12 μM，SMMC-7721细胞IC50=15 μM（48小时MTT法）[2]
- 凋亡诱导：20 μM 氟伐他汀钠 使HepG2细胞Annexin V阳性凋亡细胞比例从5%升至42%，SMMC-7721细胞从4%升至38%（Annexin V-FITC/PI双染流式细胞术）[2]
- 线粒体功能障碍：20 μM 氟伐他汀钠 使HepG2细胞线粒体膜电位（ΔΨm）降低55%（JC-1染色）；上调促凋亡蛋白Bax 2.2倍，下调抗凋亡蛋白Bcl-2 40%，激活caspase-3/caspase-9（活化型分别增加3.2倍/2.5倍，Western blot）[2]
- 选择性毒性：20 μM 氟伐他汀钠 仅使人正常肝细胞（L-02）活力降低15%，而对HepG2细胞活力降低60%，体现对肝癌细胞的选择性杀伤[2]

氟伐他汀（10 毫克/公斤/天）可降低饲喂含 1.5% 胆固醇饮食的兔子的血清脂质。氟伐他汀（10 mg/kg/天）可显着降低饲喂含 1.5% 胆固醇饮食的兔子主动脉中的组织 ACE。氟伐他汀（10 毫克/公斤/天）可显着逆转饲喂含 1.5% 胆固醇饮食的兔子对乙酰胆碱诱导的松弛的抑制。

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改善高脂饮食（HFD）喂养大鼠的动脉粥样硬化：
1. 动物：8周龄雄性SD大鼠（体重200~220 g）随机分为4组（每组n=6）：对照组（普通饲料）、模型组（高脂饲料：2%胆固醇+10%猪油）、氟伐他汀钠（Fluvastatin Sodium） 10 mg/kg/天组、20 mg/kg/天组[1]
2. 处理：高脂饲料喂养4周诱导动脉粥样硬化；氟伐他汀钠 溶于0.5% CMC-Na，每日口服灌胃（10 mL/kg），持续8周（模型组/对照组给予等量0.5% CMC-Na）[1]
3. 结果：
- 血清脂质：20 mg/kg组较模型组（模型组TC：8.2±0.9 mmol/L；LDL-C：5.6±0.7 mmol/L）降低血清总胆固醇（TC）40%、低密度脂蛋白胆固醇（LDL-C）45%[1]
- 动脉粥样硬化斑块：20 mg/kg组主动脉斑块面积减少45%（油红O染色）[1]
- 血管氧化应激：20 mg/kg组较模型组降低主动脉ROS 50%，升高主动脉HO-1活性60%[1]

VSMC氧化应激保护实验：
1. 细胞培养：大鼠胸主动脉VSMC用含10%胎牛血清（FBS）、100 U/mL青霉素和100 μg/mL链霉素的DMEM培养基，37°C、5% CO2培养，使用3~5代细胞进行实验[1]
2. 药物与应激处理：VSMC以2×105细胞/孔接种6孔板，贴壁过夜后加入氟伐他汀钠（Fluvastatin Sodium） （1 μM、5 μM、10 μM）预处理24小时，再加入200 μM H2O2诱导氧化应激6小时[1]
3. ROS检测：收集细胞，37°C孵育10 μM DCFH-DA 30分钟，流式细胞术（激发488 nm，发射525 nm）检测ROS水平[1]
4. Western blot：含蛋白酶抑制剂的RIPA缓冲液裂解细胞，30 μg蛋白经10% SDS-PAGE分离后转移至PVDF膜，孵育抗Nrf2、HO-1、NQO1及内参β-actin一抗，ImageJ定量条带强度[1]
5. 免疫荧光：VSMC接种于盖玻片，按上述处理后用4%多聚甲醛固定、0.1% Triton X-100透化，加入抗Nrf2一抗及Alexa Fluor 488标记二抗，DAPI染核，共聚焦显微镜观察Nrf2核定位[1]
- 肝癌细胞增殖与凋亡实验：
1. 细胞培养：HepG2/SMMC-7721细胞用含10% FBS的RPMI 1640培养基，人正常肝细胞L-02用含10% FBS的DMEM培养基，均在37°C、5% CO2环境培养[2]
2. 增殖检测：细胞以5×103细胞/孔接种96孔板，加入氟伐他汀钠（Fluvastatin Sodium） （2.5 μM、5 μM、10 μM、20 μM、40 μM）处理48小时，加入MTT溶液（5 mg/mL）孵育4小时，DMSO溶解甲瓒结晶后检测570 nm吸光度，计算IC50[2]
3. 凋亡检测：6孔板培养的细胞（2×105细胞/孔）经药物处理48小时后，Annexin V-FITC/PI室温染色15分钟，流式细胞术定量凋亡细胞[2]
4. 线粒体膜电位检测：细胞37°C孵育10 μM JC-1 20分钟，流式细胞术（红色荧光590 nm，绿色荧光525 nm）检测ΔΨm[2]
5. Western blot：检测Bax、Bcl-2、pro-caspase-3、cleaved-caspase-3、pro-caspase-9、cleaved-caspase-9蛋白表达[2]

Dissolved in saline; 10 mg/kg; taken with diet
Male Japanese white rabbits

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HFD-induced atherosclerotic rat model :
1. Animal housing: Male SD rats were housed under controlled conditions (22±2°C, 12-hour light/dark cycle) with free access to food and water [1]
2. Model establishment: Rats in the Model, 10 mg/kg, and 20 mg/kg groups were fed HFD (2% cholesterol, 10% lard) for 4 weeks to induce early atherosclerotic lesions; the Control group received normal chow [1]
3. Drug preparation: Fluvastatin Sodium was dissolved in 0.5% carboxymethyl cellulose sodium (CMC-Na) and sonicated for 5 minutes to form a homogeneous suspension [1]
4. Administration: Daily oral gavage (10 mL/kg) was performed for 8 weeks. The Control and Model groups received the same volume of 0.5% CMC-Na [1]
5. Sample collection and detection:
- Serum: Rats were fasted for 12 hours, blood was collected from the abdominal aorta, and serum TC/LDL-C were measured via enzymatic kits [1]
- Aorta: Rats were euthanized, aortas were dissected, and processed for Oil Red O staining (plaque area), ROS detection (DCFH-DA), HO-1 activity assay (colorimetric method), and Western blot (Nrf2) [1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No relevant published information exists on the use of fluvastatin during breastfeeding. Because of a concern with disruption of infant lipid metabolism, the consensus is that fluvastatin should not be used during breastfeeding. However, others have argued that children homozygous for familial hypercholesterolemia are treated with statins beginning at 1 year of age, that statins have low oral bioavailability, and risks to the breastfed infant are low, especially with rosuvastatin and pravastatin.[1] Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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In vitro cytotoxicity:
- Rat VSMCs: Fluvastatin Sodium (up to 20 μM, 24-hour treatment) showed no significant cytotoxicity, with cell viability >90% (MTT assay) [1]
- Human cells: 20 μM Fluvastatin Sodium reduced viability of L-02 normal hepatocytes by 15% (vs. 60% in HepG2 cells), indicating selective toxicity to hepatoma cells [2]
- In vivo safety:
- HFD-fed rats (20 mg/kg/day, 8 weeks):
- No significant body weight change (<5% vs. Control group);
- Serum liver function markers (ALT, AST) and kidney function markers (BUN, creatinine) were within normal ranges (no difference vs. Control) [1]

[1]. Makabe S, et al. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway. Atherosclerosis. 2010 Dec;213(2):377-84.
[2]. Wu Zhang, et al. Fluvastatin, a lipophilic statin, induces apoptosis in human hepatocellular carcinoma cells through mitochondria-operated pathway. Indian J Exp Biol. 2010 Dec;48(12):1167-74.

Fluvastatin Sodium is the sodium salt of a synthetic lipid-lowering agent with potential antineoplastic activity. Fluvastatin competitively inhibits hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses through the suppression of MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. Through the inhibition of mevalonate synthesis, statins, like fluvastatin, have been shown to inhibit the production of dolichol, geranylpyrophosphate (GPP) and farnesylpyrophosphate (FPP) and the isoprenylation of the intracellular G-proteins Ras and Rho, which may result in antiangiogenic, apoptotic, and antimetastatic effects in susceptible tumor cell populations.
An indole-heptanoic acid derivative that inhibits HMG COA REDUCTASE and is used to treat HYPERCHOLESTEROLEMIA. In contrast to other statins, it does not appear to interact with other drugs that inhibit CYP3A4.

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Fluvastatin Sodium is the first fully synthetic statin drug, classified as a lipophilic HMG-CoA reductase inhibitor. It is clinically approved for the treatment of hypercholesterolemia and prevention of atherosclerotic cardiovascular diseases (e.g., myocardial infarction, stroke) [1][2]
- Pleiotropic mechanisms beyond lipid lowering:
- Antioxidant protection: Activates the Nrf2-dependent antioxidant pathway in VSMCs, promoting Nrf2 nuclear translocation and upregulating antioxidant enzymes (HO-1, NQO1) to reduce oxidative stress, which contributes to atherosclerosis prevention [1]
- Antitumor potential: Induces apoptosis in hepatoma cells via the mitochondrial pathway—disrupting mitochondrial membrane potential, regulating Bax/Bcl-2 balance, and activating caspase cascades—supporting its potential as an adjuvant anticancer agent for hepatocellular carcinoma [2]
- Clinical advantage: Compared with natural statins (e.g., lovastatin), its fully synthetic nature allows for more consistent batch quality and fewer impurities related to natural sources [1][2]

C24H25FNNAO4

433.45

433.166

93957-55-2

Fluvastatin;93957-54-1;Fluvastatin-d6 sodium;(3S,5R)-Fluvastatin-d6 sodium;2249799-35-5;(3S,5R)-Fluvastatin sodium;94061-81-1

16760425

Light yellow to yellow solid powder

681.8ºC at 760 mmHg

194-197ºC

3.293

85.52

2

5

8

31

596

0

C(/C1N(C(C)C)C2C=CC=CC=2C=1C1C=CC(F)=CC=1)=C\[C@H](O)C[C@H](O)CC(=O)O.[Na]

ZGGHKIMDNBDHJB-CALJPSDSSA-M

InChI=1S/C24H26FNO4.Na/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30;/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30);/q;+1/p-1/b12-11+;

sodium;(E)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 30% propylene glycol, 5% Tween 80, 65% D5W:30 mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。