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

The enzyme hydroxymethylglutaryl-coenzyme A reductase (HMGCR), which catalyzes the rate-limiting conversion of HMG-CoA to mevalonic acid in cholesterol biosynthesis, is competitively inhibited by fluvastatin sodium (XU 62320). Studies on HCC (human hepatocellular cancer cells) show that fluvastatin causes G2/M phase arrest. HCC cells display less Bcl-2 and procaspase-9 and more Bax, cleaved caspase-3, and cytochrome c when fluvastatin (XU 62320) is present. The antilipemic drug fluvastatin (XU 62320) lowers plasma cholesterol levels and prevents cardiovascular disease.

---

Protection of vascular smooth muscle cells (VSMCs) against oxidative stress via Nrf2 pathway:
- In rat thoracic aortic VSMCs, pre-treatment with Fluvastatin Sodium (1 μM, 5 μM, 10 μM) for 24 hours concentration-dependently alleviated H2O2 (200 μM)-induced oxidative damage:
- Reactive oxygen species (ROS): 10 μM Fluvastatin Sodium reduced H2O2-induced ROS elevation by 60% (DCFH-DA fluorescence assay) [1]
- Antioxidant enzymes: 5 μM and 10 μM Fluvastatin Sodium increased heme oxygenase-1 (HO-1) protein levels by 1.8-fold and 2.5-fold, and NAD(P)H quinone dehydrogenase 1 (NQO1) by 1.5-fold and 2.1-fold, respectively (Western blot) [1]
- Nrf2 activation: 10 μM Fluvastatin Sodium increased Nrf2 nuclear translocation rate from 15% to 65% (immunofluorescence staining) and nuclear Nrf2 protein by 2.3-fold (nuclear extract Western blot) [1]
- Induction of apoptosis in human hepatocellular carcinoma cells via mitochondrial pathway:
- In HepG2 and SMMC-7721 hepatoma cells, Fluvastatin Sodium (2.5–40 μM) inhibited proliferation and induced apoptosis in a concentration-dependent manner:
- Antiproliferation: IC50 = 12 μM (HepG2) and 15 μM (SMMC-7721) (48-hour MTT assay) [2]
- Apoptosis: 20 μM Fluvastatin Sodium increased Annexin V-positive apoptotic cells from 5% to 42% (HepG2) and 4% to 38% (SMMC-7721) (flow cytometry with Annexin V-FITC/PI staining) [2]
- Mitochondrial dysfunction: 20 μM Fluvastatin Sodium reduced mitochondrial membrane potential (ΔΨm) by 55% (JC-1 staining) in HepG2 cells; upregulated Bax protein by 2.2-fold, downregulated Bcl-2 protein by 40%, and increased cleaved caspase-3/caspase-9 by 3.2-fold/2.5-fold (Western blot) [2]
- Selective toxicity: 20 μM Fluvastatin Sodium only reduced viability of normal human hepatocytes (L-02) by 15% (vs. 60% reduction in HepG2 cells), showing selective cytotoxicity to cancer cells [2]

Fluvastatin (10 mg/kg/day) results in a decrease in serum lipids in rabbits feed a 1.5% cholesterol containing diet. Fluvastatin (10 mg/kg/day) significantly lowers the tissue ACE in the aortae in rabbits feed a 1.5% cholesterol containing diet. Fluvastatin (10 mg/kg/day) significantly reverses the suppression of ACh-induced relaxation in rabbits feed a 1.5% cholesterol containing diet.

---

Attenuation of atherosclerosis in high-fat diet (HFD)-fed rats:
1. Animals: Male Sprague-Dawley (SD) rats (8 weeks old, 200–220 g) were randomized into 4 groups (n=6/group): Control (normal chow), Model (HFD: 2% cholesterol + 10% lard), Fluvastatin Sodium 10 mg/kg/day, Fluvastatin Sodium 20 mg/kg/day [1]
2. Treatment: HFD was given for 4 weeks to induce atherosclerosis; Fluvastatin Sodium (dissolved in 0.5% CMC-Na) was administered via daily oral gavage (10 mL/kg) for 8 weeks (Model/Control groups received 0.5% CMC-Na) [1]
3. Results:
- Serum lipids: 20 mg/kg group reduced serum total cholesterol (TC) by 40% and LDL-cholesterol (LDL-C) by 45% vs. Model (Model TC: 8.2 ± 0.9 mmol/L; LDL-C: 5.6 ± 0.7 mmol/L) [1]
- Atherosclerotic lesions: 20 mg/kg group reduced aortic plaque area by 45% (Oil Red O staining) [1]
- Vascular oxidative stress: 20 mg/kg group reduced aortic ROS by 50% and increased aortic HO-1 activity by 60% vs. Model [1]

VSMC oxidative stress protection assay :
1. Cell culture: Rat thoracic aortic VSMCs were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in 5% CO2. Cells at passages 3–5 were used for experiments [1]
2. Drug and stress treatment: VSMCs were seeded in 6-well plates (2×105 cells/well) and allowed to adhere overnight. Fluvastatin Sodium (1 μM, 5 μM, 10 μM) was added for 24-hour pre-incubation, followed by 200 μM H2O2 for 6-hour oxidative stress induction [1]
3. ROS detection: Cells were harvested, incubated with 10 μM DCFH-DA for 30 minutes at 37°C, and ROS levels were measured via flow cytometry (excitation 488 nm, emission 525 nm) [1]
4. Western blot: Cells were lysed with RIPA buffer (containing protease inhibitors). 30 μg of protein was separated by 10% SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against Nrf2, HO-1, NQO1, and β-actin (loading control). Band intensity was quantified via ImageJ [1]
5. Immunofluorescence: VSMCs were seeded on coverslips, treated as above, fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, and stained with anti-Nrf2 primary antibody and Alexa Fluor 488-conjugated secondary antibody. Nuclei were stained with DAPI, and Nrf2 nuclear localization was observed via confocal microscopy [1]
- Hepatoma cell proliferation and apoptosis assay :
1. Cell culture: HepG2/SMMC-7721 cells were cultured in RPMI 1640 medium (10% FBS) at 37°C, 5% CO2. Normal human hepatocytes (L-02) were cultured in DMEM medium (10% FBS) [2]
2. Proliferation assay: Cells were seeded in 96-well plates (5×103 cells/well) and treated with Fluvastatin Sodium (2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM) for 48 hours. MTT solution (5 mg/mL) was added for 4 hours, formazan was dissolved with DMSO, and absorbance at 570 nm was measured to calculate IC50 [2]
3. Apoptosis assay: Cells in 6-well plates (2×105 cells/well) were treated with Fluvastatin Sodium for 48 hours, stained with Annexin V-FITC/PI for 15 minutes at room temperature, and apoptotic cells were quantified via flow cytometry [2]
4. Mitochondrial membrane potential assay: Cells were incubated with 10 μM JC-1 for 20 minutes at 37°C, and ΔΨm was measured via flow cytometry (red fluorescence: 590 nm, green fluorescence: 525 nm) [2]
5. Western blot: Lysates were probed with antibodies against Bax, Bcl-2, pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, and β-actin [2]

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

---

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
◉ Overview of medication use during lactation There is currently no published information on the use of fluvastatin during lactation. Due to concerns about disrupting infant lipid metabolism, it is generally believed that fluvastatin should not be used during lactation. However, some scholars have pointed out that children with homozygous familial hypercholesterolemia who have been treated with statins since age 1 have low oral bioavailability and low risk to breastfed infants, especially rosuvastatin and pravastatin. [1] Until more data are available, especially during the breastfeeding period for newborns or preterm infants, other medications may be preferred. ◉ Effects on breastfed infants No published information was found as of the revision date. ◉ Effects on lactation and breast milk No published information was found as of the revision date.

---

In vitro cytotoxicity:
- Rat vascular smooth muscle cells (VSMCs): Fluvastatin sodium (concentration up to 20 μM, treatment for 24 hours) showed no obvious cytotoxicity, cell viability >90% (MTT method) [1]
- Human cells: 20 μM fluvastatin sodium reduced the viability of L-02 normal hepatocytes by 15% (HepG2 cells by 60%), indicating that it has selective toxicity to liver cancer cells [2]
- In vivo safety:
- Rats fed a high-fat diet (20 mg/kg/day, 8 weeks):
- No significant change in body weight (less than 5% change compared to the control group);
- Serum liver function indicators (ALT, AST) and kidney function indicators (BUN, creatinine) were all within the normal range (no difference compared to the control group) [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 a sodium salt of a synthetic lipid-lowering drug with potential antitumor activity. Fluvastatin competitively inhibits hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This drug lowers plasma cholesterol and lipoprotein levels and modulates immune responses by inhibiting MHC II (major histocompatibility complex II) on interferon-γ-stimulated antigen-presenting cells (such as human vascular endothelial cells). Statins (such as fluvastatin), by inhibiting mevalonate synthesis, have been shown to inhibit the production of polyterpenoids, geranyl pyrophosphate (GPP), and farnesyl pyrophosphate (FPP), as well as the isoprenelation of intracellular G proteins Ras and Rho, which may lead to anti-angiogenic, pro-apoptotic, and anti-metastatic effects in susceptible tumor cell populations. Fluvastatin sodium, an indoleheptanoic acid derivative, inhibits HMG-CoA reductase and is used to treat hypercholesterolemia. Unlike other statins, it does not appear to interact with other CYP3A4 inhibitors. Fluvastatin sodium is the first fully synthetic statin and belongs to the lipophilic HMG-CoA reductase inhibitor class. It has been clinically approved for the treatment of hypercholesterolemia and the prevention of atherosclerotic cardiovascular diseases (such as myocardial infarction and stroke)[1][2]
- Multifunctional mechanisms in addition to lipid-lowering:
- Antioxidant protection: Activates the Nrf2-dependent antioxidant pathway in vascular smooth muscle cells (VSMCs), promotes Nrf2 nuclear translocation and upregulates antioxidant enzymes (HO-1, NQO1), thereby reducing oxidative stress and helping to prevent atherosclerosis[1]
- Antitumor potential: Induces apoptosis of liver cancer cells through the mitochondrial pathway - disrupts mitochondrial membrane potential, regulates Bax/Bcl-2 balance and activates caspase cascade reaction - supports its potential as an adjuvant anticancer drug for hepatocellular carcinoma[2]
- Clinical advantages: Compared with natural statins (such as lovastatin), its fully synthetic nature makes it more stable in batch quality and has fewer impurities from 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

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W:30 mg/mL

---

 (Please use freshly prepared in vivo formulations for optimal results.)