| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| 25mg | |||
| Other Sizes |
| Targets |
The primary target of 2-hydroxy atorvastatin calcium salt is HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. Atorvastatin and its metabolites, including 2-hydroxy atorvastatin, act as competitive inhibitors of HMG-CoA reductase, binding to the active site of the enzyme and preventing the conversion of HMG-CoA to mevalonate. This inhibition leads to a decrease in cholesterol synthesis and an increase in LDL receptor expression, resulting in lower plasma cholesterol levels. The compound's IC50 for HMG-CoA reductase is 8 nM.
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| ln Vitro |
In vitro, 2-hydroxy atorvastatin calcium salt is a hydroxylated metabolite of atorvastatin that retains potent HMG-CoA reductase inhibitory activity with an IC50 of 8 nM. The compound reduces cell death induced by oxygen-glucose deprivation (OGD) in primary rat cortical neurons and increases phosphorylation of cAMP-response-element-binding protein (CREB) in GABAergic neurons. It is used in enzyme assays to study the inhibition of HMG-CoA reductase and in cell-based assays to investigate the pleiotropic effects of statins beyond cholesterol lowering, such as neuroprotection and anti-inflammatory effects.
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| ln Vivo |
In vivo, 2-hydroxy atorvastatin calcium salt is a major active metabolite of atorvastatin that contributes to the cholesterol-lowering effects of the parent drug. Atorvastatin and its metabolites are widely used in animal models of hyperlipidemia to study their pharmacokinetics and efficacy. The compound's effects on cholesterol levels, vascular function, and inflammation have been studied in various animal models. Its neuroprotective effects have also been investigated in models of ischemic stroke. Further studies are needed to fully characterize its specific in vivo effects.
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| Enzyme Assay |
Cell-free assays for 2-hydroxy atorvastatin calcium salt typically involve assessing its inhibition of HMG-CoA reductase. A common protocol involves incubating the enzyme with HMG-CoA, NADPH, and various concentrations of the compound in a reaction buffer at 37degC. The reaction is stopped, and the amount of mevalonate produced is measured using a spectrophotometric or radioactive assay. The IC50 value is determined by plotting the percentage of enzyme activity remaining against the compound concentration. The compound's binding affinity to the enzyme can be assessed using surface plasmon resonance (SPR) or other biophysical methods.
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| Cell Assay |
For in vitro cellular experiments, cells (e.g., hepatocytes, neuronal cells, vascular smooth muscle cells) are cultured in appropriate media and treated with 2-hydroxy atorvastatin calcium salt at various concentrations (typically 0.1-100 uM). For cholesterol synthesis studies, cells are incubated with the compound, and cholesterol levels are measured using enzymatic assays or LC-MS. For neuroprotection studies, cells are subjected to oxygen-glucose deprivation (OGD) in the presence or absence of the compound, and cell viability is assessed using MTT or LDH assays. Signaling pathway activation, such as CREB phosphorylation, is assessed by Western blot.
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| Animal Protocol |
In vivo animal experiments with 2-hydroxy atorvastatin calcium salt typically involve oral administration in rodent models of hyperlipidemia. A common dosing regimen is 1-50 mg/kg body weight, administered daily for 1-4 weeks. Blood samples are collected to measure plasma cholesterol, triglyceride, and lipoprotein levels. For neuroprotection studies, animals are subjected to cerebral ischemia, and the compound is administered before or after the ischemic event. Neurological function and infarct size are assessed. Pharmacokinetic studies are performed by collecting blood samples at various time points and measuring plasma drug concentrations by LC-MS/MS.
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| ADME/Pharmacokinetics |
2-Hydroxy atorvastatin calcium salt has a molecular weight of approximately 1200 g/mol (calcium salt form) and a molecular formula of C66H68CaF2N4O12. As a metabolite of atorvastatin, its pharmacokinetic properties are similar to those of the parent drug. Atorvastatin is orally bioavailable and has a half-life of approximately 14 hours. The compound is primarily metabolized in the liver by CYP3A4 and is excreted in the bile. Its pharmacokinetic profile is characterized by dose-dependent exposure and extensive tissue distribution.
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| Toxicity/Toxicokinetics |
The toxicity profile of 2-hydroxy atorvastatin calcium salt is similar to that of atorvastatin, which is generally well-tolerated at therapeutic doses. Common adverse effects associated with statin therapy include myalgia, elevated liver enzymes, and gastrointestinal disturbances. Rare but serious adverse effects include myopathy and rhabdomyolysis. The compound should be handled with standard laboratory precautions and is intended for research use only.
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| References | |
| Additional Infomation |
2-Hydroxy atorvastatin calcium salt (CAS 265989-46-6) is a hydroxylated metabolite of atorvastatin calcium salt, a potent HMG-CoA reductase inhibitor with an IC50 of 8 nM. It is formed from atorvastatin by CYP3A4. The compound retains HMG-CoA reductase inhibitory activity and is used in pharmacological research to study statin metabolism, pharmacokinetics, and efficacy. It also exhibits neuroprotective effects by reducing cell death induced by oxygen-glucose deprivation in neurons. 2-Hydroxy atorvastatin calcium salt is available as a research compound and is not approved for clinical use.
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| Molecular Formula |
C33H34CAFN2O6
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|---|---|
| Molecular Weight |
613.709271907806
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| Exact Mass |
613.203
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| CAS # |
265989-46-6
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| Related CAS # |
214217-86-4 (free acid);265989-46-6 (calcium);
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| PubChem CID |
73208804
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| Appearance |
White to off-white solid powder
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| LogP |
6.841
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
85
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| Complexity |
856
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NOCWNJZXNVSDOU-UHFFFAOYSA-L
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| InChi Code |
InChI=1S/2C33H35FN2O6.Ca/c2*1-20(2)31-30(33(42)35-26-10-6-7-11-27(26)39)29(21-8-4-3-5-9-21)32(22-12-14-23(34)15-13-22)36(31)17-16-24(37)18-25(38)19-28(40)41;/h2*3-15,20,24-25,37-39H,16-19H2,1-2H3,(H,35,42)(H,40,41);/q;;+2/p-2
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| Chemical Name |
calcium;7-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-phenyl-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~12.5 mg/mL (~21.02 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.27 mg/mL (3.82 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 22.7 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: ≥ 1.25 mg/mL (2.10 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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6294 mL | 8.1472 mL | 16.2943 mL | |
| 5 mM | 0.3259 mL | 1.6294 mL | 3.2589 mL | |
| 10 mM | 0.1629 mL | 0.8147 mL | 1.6294 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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