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| 1mg |
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| Other Sizes |
| Targets |
Like rosuvastatin, N-desmethyl rosuvastatin targets the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the rate‑controlling enzyme in the hepatic cholesterol biosynthesis pathway. It competitively binds to the active site of HMGCR, inhibiting the conversion of HMG-CoA to mevalonate. However, its inhibitory potency is significantly lower than that of the parent drug. The metabolite also retains the ability to interact with organic anion transporting polypeptides (e.g., OATP1B1 and OATP1B3), which mediate hepatic uptake, but to a lesser extent than rosuvastatin.
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| ln Vitro |
In vitro cell-free enzymatic assays using purified human HMGCR demonstrate that N-desmethyl rosuvastatin has approximately 17‑50% of the inhibitory activity of rosuvastatin. For comparison, rosuvastatin has an IC50 in the range of 0.16-11 nM. The exact IC50 value for the metabolite has not been published, but it is generally reported as an “active but weaker” inhibitor. The compound does not show significant off-target inhibition against other enzymes at relevant concentrations.
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| ln Vivo |
As a metabolite, N-desmethyl rosuvastatin is not administered as a free agent in therapeutic animal models. However, its in vivo activity is inferred from the pharmacodynamic effects of rosuvastatin. In animal models (e.g., hypercholesterolemic rats or mice), rosuvastatin treatment results in dose-dependent lowering of LDL cholesterol and upregulation of LDL receptor expression, and the metabolite contributes to this effect to a minor extent. For isolated administration of the metabolite, prospective studies would use oral doses (e.g., 1‑3 mg/kg) and measure changes in serum mevalonate, cholesterol synthesis, and hepatic LDLR expression, but such data are not available.
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| Enzyme Assay |
The standard cell-free assay for HMG-CoA reductase inhibition uses recombinant human HMGCR catalytic domain. The metabolite is dissolved in DMSO and diluted in reaction buffer (e.g., 0.1 M potassium phosphate, pH 7.4, 1 mM DTT, 0.1% BSA). Reactions are performed in 96‑well plates: add 50 uL of enzyme solution (5 ng/well), 25 uL of compound at various concentrations (0.1‑1000 nM), and 25 uL of NADPH (0.2 mM final). After a 10‑min pre-incubation, 25 uL of HMG-CoA (5 uM final) is added. The reaction proceeds for 30 min at 37degC and is terminated by adding 25 uL of 1 M HCl. Mevalonate is quantitated by a coupled enzyme assay (mevalonate kinase, pyruvate kinase, lactate dehydrogenase) measuring NADH oxidation at 340 nm. IC50 values are calculated using a four‑parameter logistic curve.
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| Cell Assay |
Because N-desmethyl rosuvastatin is primarily used as a reference standard for LC‑MS/MS quantification, dedicated cellular activity assays are not routinely performed. However, a general in vitro cellular protocol for statin activity can be adapted: primary human hepatocytes or HepG2 cells are seeded in 24‑well plates (2×10⁵ cells/well) in Williams' E medium. After 24 h, cells are treated with serial dilutions of the metabolite (0.01‑10 uM) for 18 h. HMG-CoA reductase activity is measured by incubating cell lysates with 14C-HMG-CoA and NADPH, followed by separation of 14C‑mevalonate by TLC. The percentage inhibition is calculated relative to vehicle control. Alternatively, LDLR protein expression is measured by Western blot. These protocols are standard for statin pharmacology but have not been validated specifically for this metabolite.
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| Animal Protocol |
In vivo animal protocols for studying N-desmethyl rosuvastatin are typically part of rosuvastatin PK/PD studies. A representative protocol in rats: male Sprague-Dawley rats (200‑250 g) are fasted overnight and administered rosuvastatin (5 mg/kg) or the metabolite alone (if available, e.g., 1 mg/kg) by oral gavage. Blood samples (200 uL) are collected via jugular vein cannula at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose. Plasma is separated and frozen at -80degC. After protein precipitation with acetonitrile, concentrations of N-desmethyl rosuvastatin are determined by LC‑MS/MS. To assess biliary excretion, bile duct‑cannulated rats are used. For metabolic pathway identification, radiolabeled rosuvastatin (14C) is administered, and bile, urine, and feces are collected for 48‑72 h, followed by radio-HPLC to detect the metabolite.
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| ADME/Pharmacokinetics |
After oral administration of rosuvastatin in humans, N-desmethyl rosuvastatin reaches peak plasma concentration (Cmax) approximately 3‑5 hours post-dose. Its Cmax is typically 5‑15% that of rosuvastatin, and its AUC0-∞ is proportionally low. The metabolite exhibits a mean elimination half‑life (t1/2) of approximately 6‑9 hours (slightly shorter than rosuvastatin's 19 hours). Its formation is CYP2C9-dependent, and it is eliminated primarily via biliary excretion (feces), with minimal renal excretion. In drug-drug interaction studies with CYP2C9 inhibitors (e.g., resmetirom, fluconazole), the exposure (AUC) of N-desmethyl rosuvastatin may decrease due to altered parent availability or direct metabolic inhibition, with half‑life often being shortened.
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| Toxicity/Toxicokinetics |
No specific toxicology data are available for N-desmethyl rosuvastatin as an isolated compound. However, as an active metabolite of rosuvastatin, it is expected to share the same class‑specific toxicities: generally well‑tolerated at therapeutic plasma levels, with rare but potential adverse effects including mild transaminase elevation, myopathy, and in very rare cases, rhabdomyolysis. In preclinical rodent studies, high doses of rosuvastatin (≥80 mg/kg/day) cause myopathy and hepatotoxicity; the metabolite likely contributes only minimally. For research handling, standard precautions apply: avoid inhalation, ingestion, skin/eye contact; use PPE; work in a fume hood. It is not classified as a highly hazardous substance.
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| References | |
| Additional Infomation |
Molecular formula: C21H2₆FN3Na2O₇S (disodium salt hydrate). Molecular weight: 529.49 g/mol. Appearance: white to off-white solid. Purity: typically ≥95% by HPLC. Solubility: soluble in DMSO, water, and methanol. Storage: powder at -20degC, protected from light and moisture; solutions in DMSO or water at -80degC for up to 6 months. N-Desmethyl rosuvastatin is the primary major circulating active metabolite of rosuvastatin and is used as a reference standard in pharmacokinetic, drug‑drug interaction, and bioequivalence studies. It is for research use only, not for clinical or diagnostic applications.
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| Molecular Formula |
C21H26FN3NA2O7S
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| Molecular Weight |
529.49
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8886 mL | 9.4430 mL | 18.8861 mL | |
| 5 mM | 0.3777 mL | 1.8886 mL | 3.7772 mL | |
| 10 mM | 0.1889 mL | 0.9443 mL | 1.8886 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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