HMG-CoA reductase (Ki = 1.3 nM/L)
HMG-CoA reductase (3-hydroxy 3-methylglutaryl coenzyme A reductase). This inhibition prevents the synthesis of cholesterol precursors farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are responsible for the prenylation and membrane translocation of Ras and RhoA, respectively. [1]

Treatment with cerivastatin (5–50 ng/mL; 3 days; MDA-MB-231 cells) reduced MDA-MB-231 cell proliferation in a dose-dependent manner, with up to 40% reduction observed at 25 ng/mL [1]. After 36 hours of treatment, cerivastatin (25 ng/mL; 18–36 hours; MDA-MB-231 cells) induced cell cycle arrest in the G1/S phase. At shorter incubation durations (18 hours), this standstill was not seen [1]. The administration of cerivastatin (25 ng/mL; 18 hours; MDA-MB-231 cells) significantly raises the levels of p21Waf1/Cip1 [1]. In MDA-MB-231 cells, cerivastatin administration (25 ng/mL; 12 hours) enhances p21 transcripts [1]. Matrigel-mediated MDA-MB-231 cell invasion is inhibited by ciprivastatin (10–25 ng/mL; 18 hours) [1]. Cerivastatin (25 ng/mL; 18–36 hours) causes morphological alterations and delocalizes Ras and RhoA from the cell membrane to the cytoplasm [1]. In a RhoA inhibition-dependent manner, cerivastatin (25 ng/mL; 4-36 hours) promotes NFκB inactivation, which leads to a decrease in the expression of urokinase and metalloproteinase 9, and an increase in IκB concurrently [1].

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In MDA-MB-231 cells (aggressive breast cancer line), Cerivastatin induced a dose-dependent decrease in cell proliferation, with up to 40% inhibition at 25 ng/ml. A cytotoxic effect was observed at 50 ng/ml, accompanied by cell detachment. This anti-proliferative effect was fully reversible by co-incubation with mevalonate (MVA, 100 μM) or GGPP (10 μM), but not by FPP (10 μM). [1]
Cerivastatin (25 ng/ml for 36 h) induced an arrest of the cell cycle in G1/S phase (67.1% in treated cells vs. 58.9% in controls) without inducing apoptosis, as confirmed by absence of Annexin V binding, propidium iodide incorporation, DNA fragmentation, and pre-G1 peak increment. [1]
Cerivastatin increased p21Waf1/Cip1 mRNA and nuclear protein levels in MDA-MB-231 cells after 12-18 h treatment. This increase was reversed by MVA and GGPP, but not by FPP. [1]
Cerivastatin dose-dependently inhibited MDA-MB-231 cell invasion through Matrigel, with a plateau at 25 ng/ml (54 ± 5.1% inhibition of migration, P<0.01) after 18 h. This effect was rescued by MVA and GGPP, but not FPP. [1]
Cerivastatin (25 ng/ml for 18 h) caused delocalization of RhoA from the cell membrane to the cytoplasm, which was reversed by GGPP but not FPP. This was associated with disorganization of actin fibers and loss of focal adhesion sites. Delocalization of Ras was partial and only observed after 36 h. [1]
Cerivastatin decreased constitutive NFκB DNA-binding activity in MDA-MB-231 cells in a time-dependent manner, beginning at 18 h and complete at 36 h. This was associated with translocation of the RelA (p65) subunit from the nucleus to the cytoplasm and an increase in IκB protein in the cytoplasm. The effect on NFκB was reversed by GGPP, but not FPP. [1]
Cerivastatin (25 ng/ml for 18 h) decreased Tissue Factor (TF) expression on the MDA-MB-231 cell surface by 63%. A significant decrease in urokinase plasminogen activator (u-PA) expression (59% at 25 ng/ml) was observed only after 2 days of treatment. [1]
Cerivastatin dose-dependently reduced MMP-9 (92 kDa type IV collagenase) secretion by MDA-MB-231 cells after 36 h treatment, without affecting TIMP-1 secretion. [1]
In contrast, Cerivastatin treatment (up to 25 ng/ml) did not significantly modify proliferation, NFκB activity, TF/u-PA expression, or cell shape in poorly invasive MCF-7 cells. [1]

Cerivastatin is readily absorbed and reaches peak plasma concentrations one to three hours after oral treatment. Cerivastatin has a 2-4 hour half-life of elimination in the circulation and is highly bound to plasma proteins (99.5%). Three polar metabolites are primarily produced by the liver's metabolism of cerivastatin. The third metabolite is inert, and the other two are active but not as active as the original medication. All of the metabolites' plasma concentrations were noticeably lower than the parent drug's. While practically no parent compound is expelled, metabolites are removed through urine (20–25%) and feces (66-73%) [2].

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In patients with primary hypercholesterolemia, Cerivastatin 0.2 mg once daily (with evening meal or at bedtime) for 4 weeks produced the following mean percent changes from baseline: total cholesterol -21.9% to -22.1%, LDL cholesterol -29.4% to -30.4%, HDL cholesterol +2.3% to +3.2%, triglycerides -10.9% to -11.6%, direct LDL cholesterol -26.6% to -27.4%, VLDL cholesterol -12.7% to -13.3%, apolipoprotein B -23.0% to -23.9% [2].

The 0.2 mg bedtime dose resulted in 8.1% of subjects with <15% LDL-C reduction, 75.6% with 15-40% reduction, and 16.3% with >40% reduction [2].

LDL-C reduction was greater in females, older patients (>60 years), and non-smokers, while lesser reductions were associated with current smoking and higher body weight [2].

Treatment response was observed by 1 week and maximal by 3 weeks of therapy [2].

Electrophoretic Mobility Shift Assay (EMSA) for NFκB: Nuclear proteins (10 μg) were incubated with a 32P 5'-end-labeled oligonucleotide coding for the tandem κB sequence. The resulting protein-oligonucleotide complexes were resolved by 6% PAGE and visualized by autoradiography. For supershift assays, nuclear extracts were preincubated with antibodies against RelA (p65), p50, RelB, or c-Rel before the binding reaction. [1]
SDS-PAGE Zymography for MMP-9: Conditioned medium (10 μl/lane) from MDA-MB-231 cells was electrophoresed on 7.5% polyacrylamide gels containing 10% SDS and gelatin (1 mg/ml) under nonreducing conditions. After electrophoresis, SDS was removed by washing in 2.5% Triton X-100. Gelatinase activity was revealed overnight at 37°C in a buffer containing 50 mM Tris-HCl and 5 mM CaCl2. Gels were stained with Coomassie Blue R250, and gelatinolytic activity was observed as clear bands. [1]

Cell proliferation assay[1]
Cell Types: MDA-MB-231 Cell
Tested Concentrations: 5 ng/mL, 10 ng/mL, 25 ng/mL, 50 ng/mL
Incubation Duration: 3 days
Experimental Results: Induction of MDA-MB-231 cells of cell proliferation.

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Cell cycle analysis [1]
Cell Types: MDA-MB-231 Cell
Tested Concentrations: 25 ng/mL
Incubation Duration: 18 hrs (hours), 36 hrs (hours)
Experimental Results: Induced cell cycle arrest in G 1/S phase.

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Western Blot Analysis[1]
Cell Types: MDA-MB-231 Cell
Tested Concentrations: 25 ng/mL
Incubation Duration: 18 hrs (hours)
Experimental Results: A significant increase in p21Waf1/Cip1 levels was induced.

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RT-PCR[1]
Cell Types: MDA-MB-231 Cell
Tested Concentrations: 25 ng/mL
Incubation Duration: 12 hrs (hours)
Experimental Results: Increased p21Waf1/Cip1 mRNA levels.

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Cell Proliferation Assay: Cells (5x10⁴ cells/well) were seeded in a 24-well plate and incubated with Cerivastatin in 2% fetal calf serum. Cell number was measured on day 3 for MDA-MB-231 and on day 5 for MCF-7 cells using a particle counter after detachment with a non-enzymatic cell dissociation solution. [1]
Apoptosis Analysis (Annexin V/PI): Cells were washed in PBS and incubated with FITC-conjugated annexin V for 15 min at 4°C. Staining with propidium iodide (0.3 μg/ml) was performed to assess cell membrane permeability. [1]
DNA Fragmentation Assay: Genomic DNA was isolated, precipitated, and resuspended. An aliquot of each DNA sample was analyzed on a 2% agarose gel stained with ethidium bromide to visualize oligonucleosomal fragments. [1]
Cell Cycle Analysis: Nuclei were prepared using the Vindelov technique. Cells were treated with trypsin (30 μg/ml), followed by trypsin inhibitor (0.5 mg/ml) and RNase A (0.1 mg/ml). Nuclei were stained with propidium iodide (0.4 mg/ml) and analyzed by flow cytometry. [1]
ELISA for p21Waf1/Cip1: Measurement of p21WAF1/Cip1 antigen in the nuclear fraction was performed using a commercial ELISA kit according to the manufacturer's instructions. [1]
Invasion Assay: Cells (5x10⁴) were seeded in the upper chamber of a Transwell insert (12 μM pores) coated with Matrigel (diluted 1:100). The lower chamber contained basic fibroblast growth factor (20 ng/ml) to induce chemotaxis. After 18 h, non-migrated cells were scraped away, and invaded cells on the lower surface were stained with May-Grünwald-Giemsa. [1]
Confocal Microscopy: Cells were fixed with 3.5% paraformaldehyde and permeabilized with 1% Triton X-100. Ras and RhoA were detected using primary monoclonal antibodies (2 μg/ml), followed by a FITC-conjugated secondary antibody. Actin filaments were visualized with TR/TC labelled phalloidin. [1]
Immunofluorescence for NFκB: Fixed and permeabilized cells were incubated with a polyclonal primary antibody against RelA (1 μg/ml), followed by a FITC-conjugated secondary antibody. Green fluorescence was visualized with a fluorescence microscope. [1]
Western Blot: Cytoplasmic or nuclear extracts (20 μg protein) were subjected to SDS-PAGE. Proteins were electrotransferred onto PVDF membranes. Binding of primary antibodies against IκBα or p21Waf1/Cip1 was detected with an enhanced chemiluminescence visualization system using a horseradish peroxidase-coupled secondary antibody. [1]
Flow Cytometry for TF and u-PA: For TF, cells were incubated with FITC-conjugated anti-TF antibody. For u-PA, cells were first incubated with a primary anti-u-PA antibody, followed by a FITC-conjugated secondary antibody. Expression was analyzed by flow cytometry. [1]
RT-PCR for p21Waf1/Cip1: Total RNA was extracted. RT-PCR was performed using specific primers for p21Waf1/Cip1 (sense: 5'-CGGAGCTGGGCGCGGATTGC-3', antisense: 5'-GGAAGCGGCGAGGGCCTCAAA-3') and β-actin. PCR products (592 bp for p21, 838 bp for β-actin) were size fractionated on a 2% agarose gel stained with ethidium bromide. [1]

Reduction of serum cholesterol, most notably low-density lipoprotein cholesterol is associated with reductions in cardiovascular morbidity and mortality. Statins have been shown to effectively reduce low-density lipoprotein cholesterol via inhibition of the hydroxymethyl-coenzyme A (HMG-CoA) reductase. Cerivastatin is the most potent HMG-CoA reductase inhibitor currently under study in the United States. METHODS AND RESULTS: A parallel group, randomized, placebo-controlled, double-blind, multicenter study was conducted to compare the efficacy and safety of three different dosing regimens of 0.2 mg/day of cerivastatin, a new HMG-CoA reductase inhibitor, in patients with hypercholesterolemia. After a 10-week diet-placebo lead-in period, 319 patients with low-density lipoprotein cholesterol >160 mg/dL were randomized to 4 weeks of treatment with one of the following regimens: cervastatin 0.1 mg twice daily, cerivastatin 0.2 mg once daily with the evening meal, cerivastatin 0.2 mg once daily at bedtime or placebo. All three active treatment groups produced statistically significant (P <.05) changes compared to aseline and placebo in total cholesterol (0.1 mg twice daily _18.9%; 0.2 mg once daily with the evening meal: _21.9%; 0.2 mg once daily at bedtime: _22.1%; placebo: 0.0%), low-density lipoprotein cholesterol (0.1 mg twice daily: _25.7%; 0.2 mg once daily with the evening meal: _29.4%; 0.2 mg once daily at bedtime: _30.4%; placebo: 1.4%) and high-density lipoprotein cholesterol (0.1 mg twice daily: 5.3%; 0.2 mg once daily with the evening meal: baseline and placebo, were also reduced by all active treatments (0.1 mg twice daily: _11.6% [P =.05]; 0.2 mg once daily with the evening meal: _11.6% [P =.05]; and 0.2 mg at bedtime: _10.9% [P =.07]). The percentage change in total cholesterol and low-density lipoprotein cholesterol after 4 weeks of therapy for the once-daily cerivastatin groups was statistically significantly greater (P <.05) than the cerivastatin twice daily regimen. A treatment responser was seen by 1 week of therapy and was maximal by 3 weeks. The drug was well tolerated in all three dosing regimens and resulted in no significant increase in biochemical or clinical side effects compared to placebo. CONCLUSION: Cerivastatin is a novel, highly potent, well-tolerated HMG-CoA reductase inhibitor that produces low-density lipoprotein cholesterol reductions of approximately 30% when administered at 0.2 mg once a day in the evenings.[2]

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Absorption, Distribution and Excretion
The mean absolute oral bioavailability is 60% (range 39% - 101%). Protein binding: Very high (>99%) (80% bound to albumin). Bioavailability: 60% (range 39% - 10%). Excretion: Feces (bile): 70%. Kidney: 24%. Time to peak concentration: Approximately 2.5 hours. For more complete data on absorption, distribution, and excretion of cerivastatin (8 items), please visit the HSDB record page. Metabolism/Metabolites Hepatic metabolism. The biotransformation pathways of cerivastatin in humans include: demethylation of benzyl methyl ether to M1, and methyl hydroxylation. The 6'-isopropyl moiety forms M23. Administered in its active (open acid) form. Biotransformation occurs via demethylation and hydroxylation. Certain metabolites (M1 and M23) possess pharmacological activity, with relative potencies of 50% and 100% of the parent compound, respectively. Cerivastatin is metabolized by CYP3A4 and CYP2C8; however, the drug appears to have a higher affinity for the latter enzyme. /HMG-CoA reductase inhibitor/ Known human metabolites of cerivastatin include (E)-7-[4-(4-fluorophenyl)-5-(hydroxymethyl)-2,6-di(propyl-2-yl)pyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid and (E)-7-[4-(4-fluorophenyl)-6-(1-hydroxypropyl-2-yl)-5-(methoxymethyl)-2-propyl-2-ylpyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid. Biological half-life: 2–3 hours. Elimination: 2–3 hours.

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Cerivastatin is well absorbed, reaching maximal plasma levels 1-3 hours after oral dosing [2].

Plasma protein binding is 99.5% [2].

Elimination half-life is 2-4 hours [2].

Metabolized predominantly in the liver to three polar metabolites; two metabolites are active (to a lesser extent than parent drug), the third is inactive [2].

Metabolites are excreted via urine (20-25%) and feces (66-73%); essentially no parent compound is excreted [2].

Multiple daily dosing of 0.1 to 0.4 mg showed no significant effect on absorption or metabolism, and no drug accumulation [2].

Pharmacokinetic studies in males and females aged 18-45 years and 65-85 years indicated no relevant differences in metabolism [2].

Protein Binding
Over 99% of circulating drugs are bound to plasma proteins (80% to albumin). Interactions
Cerivastatin is contraindicated with azole antifungals, cyclosporine, gemfibrozil, other fibrates, immunosuppressants, macrolide antibiotics, or niacin due to rhabdomyolysis and associated renal failure. Concomitant use with cholestyramine or colestipol may reduce the bioavailability of HMG-CoA reductase inhibitors; therefore, when these drugs are used in combination with HMG-CoA reductase inhibitors to enhance therapeutic effects, it is recommended to take the HMG-CoA reductase inhibitor 2 to 4 hours after taking cholestyramine or colestipol. Concomitant use of cerivastatin and gemfibrozil is contraindicated due to the potential for rhabdomyolysis. /HMG-CoA Reductase Inhibitors/
Some patients have experienced myopathy and/or rhabdomyolysis when taking cyclosporine and certain statins concurrently. Although the mechanism of this interaction is not fully elucidated, studies suggest that this adverse reaction may be due to cyclosporine inhibiting the metabolism of statins (via the cytochrome P450 isoenzyme CYP3A4). Concomitant use of cyclosporine and cerivastatin can result in a 3- to 5-fold increase in plasma concentrations of the lipid-lowering drug. /HMG-CoA Reductase Inhibitors/
For more complete data on interactions of CERIVASTATINs (9 in total), please visit the HSDB records page.

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Cerivastatin was withdrawn from the market due to 52 deaths attributed to drug-related rhabdomyolysis that led to kidney failure (31 fatalities in the United States and 21 deaths worldwide). [3]
There were 385 nonfatal cases of rhabdomyolysis reported among the estimated 700,000 users in the United States, most of whom required hospitalization. [3]
The risk of rhabdomyolysis was found to be higher among patients who received the full dose of Cerivastatin (0.8 mg/day). [3]
The risk was also higher among patients who received gemfibrozil concomitantly; this drug-drug interaction was implicated in 12 of the 31 fatalities in the United States. [3]
Rhabdomyolysis was 10 times more common with Cerivastatin than with the other five approved statins (lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin). [3]

[1]. Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study. Carcinogenesis. 2001 Aug;22(8):1139.

[2]. Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With Primary Hypercholesterolemia. J Cardiovasc Pharmacol Ther. 1997 Jan;2(1):7-16.

[3]. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2(5):205-207.

Cerivastatin is (3R,5S)-3,5-dihydroxyhept-6-enoic acid, where the (7E)-hydrogen is replaced by 4-(4-fluorophenyl)-2,6-diisopropyl-5-(methoxymethyl)pyridin-3-yl. It was previously used in sodium form to lower cholesterol and prevent cardiovascular disease, but was withdrawn globally in 2001 due to reports of severe muscle toxicity. It belongs to the pyridine class of compounds, dihydroxy monocarboxylic acids, and statins (synthetic). It is the conjugate acid of cerivastatin (1-). On August 8, 2001, the U.S. Food and Drug Administration (FDA) announced that Bayer Pharmaceuticals had voluntarily withdrawn Baycol from the U.S. market due to reports of fatal rhabdomyolysis associated with the cholesterol-lowering (lipid-lowering) product. The drug had also been withdrawn from the Canadian market. Cerivastatin is a synthetic lipid-lowering drug. Cerivastatin competitively inhibits hepatic hydroxymethylglutaryl-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 the immune response by inhibiting major histocompatibility complex II on interferon-γ-stimulated antigen-presenting cells (such as human vascular endothelial cells). Muscle toxicity (myopathy and rhabdomyolysis) limits its clinical application. Drug Indications For adjunctive dietary therapy to reduce elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson type IIa and IIb), particularly when dietary restriction of saturated fat and cholesterol alone is ineffective, as are other non-pharmacological treatments.
FDA Label

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Mechanism of Action
Cerivastatin competitively inhibits hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonate in the liver. Since mevalonate is a precursor to sterols such as cholesterol, this leads to decreased cholesterol levels in hepatocytes, upregulation of low-density lipoprotein (LDL) receptors, and increased uptake of LDL cholesterol from the circulation by the liver.
When statins are used in combination with fibrates or niacin, myopathy may be due to enhanced inhibition of skeletal muscle sterol synthesis (a pharmacodynamic interaction). /Statins/
Statins are a class of lipid-lowering drugs that competitively inhibit hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early precursor to cholesterol. These drugs have structures similar to HMG-CoA and selectively and reversibly competitively inhibit HMG-CoA reductase. The high affinity of statins for HMG-CoA reductase is likely due to their binding to two different sites on the enzyme. /HMG-CoA Reductase Inhibitors/

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Therapeutic Use
Hydroxymethylglutaryl-CoA reductase inhibitors
Drug: Anti-hyperlipoproteinemia
On August 8, 2001, the U.S. Food and Drug Administration (FDA) announced that Bayer Pharmaceuticals voluntarily withdrew its drug, cerivastatin, from the U.S. market because reports indicated that the cholesterol-lowering (lipid-lowering) product could sometimes cause fatal muscle adverse reactions such as rhabdomyolysis. The FDA agreed to and supported this decision.
Antibiotic and antibacterial activity against Trichomonas vaginalis and Entamoeba histolytica.
Drug Warnings
On August 8, 2001, the FDA announced that Bayer Pharmaceuticals had voluntarily withdrawn Beco (cerivastatin) from the U.S. market because the cholesterol-lowering (lipid-lowering) product had been reported to cause rhabdomyolysis, a serious muscle adverse reaction that can sometimes be fatal. The FDA agreed to and supported this decision.
FDA Pregnancy Risk Class: X / Contraindicated during pregnancy. Animal or human studies, or investigational or post-marketing reports, have demonstrated a risk of fetal malformation or injury that significantly outweighs any potential benefit to the patient. /
Cerivastatin (Beco)...should be taken at bedtime, several hours after taking a bile acid sequestrant.
...The incidence of myopathy increases when the dose of statins exceeds 25% of the maximum dose...when used in combination with niacin. /Statins/
For more complete data on drug warnings for cerivastatin (17 total), please visit the HSDB records page.

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Pharmacodynamics
Cerivastatin is a competitive HMG-CoA reductase inhibitor that effectively lowers LDL cholesterol and triglycerides and is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson IIa and IIb).

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Cerivastatin (Baycol® or Lipobay®) was recently withdrawn from the world market. At the time of withdrawal, Baycol® had slightly less than 4% of the statin market in the United States. [3]
Cerivastatin received initial regulatory approval based on its effects on serum lipoproteins (surrogate efficacy), not on long-term clinical outcome trials. [3]
The authors state that all statins are not interchangeable; Cerivastatin is at least 10 times more likely than the other statins to cause fatal rhabdomyolysis. [3]
The clinical benefit of Cerivastatin was unproven at the time of withdrawal. [3]
The withdrawal of Cerivastatin erodes public confidence in the medical care system. [3]

C26H34FNO5

459.56

441.232

C, 67.95; H, 7.46; F, 4.13; N, 3.05; O, 17.41

145599-86-6

Cerivastatin sodium;143201-11-0

446156

Typically exists as solid at room temperature

1.181 g/cm3

646.3ºC at 760 mmHg

344.7ºC

0mmHg at 25°C

1.594

5.36

3

7

11

33

620

2

O=C(C[C@@H](C[C@@H](/C=C/C1=C(C(C)C)N=C(C(C)C)C(COC)=C1C1=CC=C(F)C=C1)O)O)[O-]

SEERZIQQUAZTOL-ANMDKAQQSA-N

InChI=1S/C26H34FNO5/c1-15(2)25-21(11-10-19(29)12-20(30)13-23(31)32)24(17-6-8-18(27)9-7-17)22(14-33-5)26(28-25)16(3)4/h6-11,15-16,19-20,29-30H,12-14H2,1-5H3,(H,31,32)/b11-10+/t19-,20-/m1/s1

(E,3R,5S)-7-[4-(4-Fluorophenyl)-5-(methoxymethyl)-2,6-di(propan-2-yl)pyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid

Cerivastatin; Baycol; BAY-w-6228; BAY-w 6228; cerivastatin; 145599-86-6; cerivastatin acid; Lipobay; AM91H2KS67; CHEBI:3558; Cerivastatin (INN); (3R,5S,6E)-7-(4-(4-Fluorophenyl)-5-(methoxymethyl)-2,6-bis(1-methylethyl)-3-pyridinyl)-3,5-dihydroxy-6-heptenoic acid; BAY-w6228; Cerivastatin Sodium; Rivastatin; Lipobay

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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