| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
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| Other Sizes |
| Targets |
ent-Atorvastatin targets the pregnane X receptor (PXR), a nuclear receptor involved in the regulation of drug-metabolizing enzymes. It also interacts with HMG-CoA reductase but lacks inhibitory activity against this enzyme. The compound activates PXR, leading to increased expression of cytochrome P450 enzymes such as CYP2B and CYP3A.
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| ln Vitro |
CYP2B and CYP3A mRNA levels are increased equally by atorvastatin and its inactive enantiomer (3S,5S)-atorvastatin [1]. At a dose of 100 μM, (3S,5S)-atorvastatin causes luciferase activity, with an EC50 of 12.4 μM [2]. When 3-formylphenylboronic acid (FPBA)/l-tryptophan is added to a mixture, the intensity of l-tryptophan's fluorescence increases [3].
In vitro, ent-Atorvastatin exhibits little or no inhibitory activity against HMG-CoA reductase, in stark contrast to the active (3R,5R) enantiomer. It activates PXR and increases CYP2B and CYP3A mRNA levels equally to atorvastatin. At a dose of 100 μM, ent-Atorvastatin causes luciferase activity with an EC50 of 12.4 μM in reporter assays. It also exhibits antifungal properties against Candida albicans by reducing ergosterol levels. |
| ln Vivo |
In vivo activity data for ent-Atorvastatin are limited in publicly available literature. As an inactive enantiomer of atorvastatin, it does not produce cholesterol-lowering effects through HMG-CoA reductase inhibition. However, its PXR activation properties may influence drug metabolism in vivo. The compound has been studied in primary rat hepatocyte cultures to assess its effects on cytochrome P450 enzyme expression.
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| Enzyme Assay |
The in vitro receptor binding assay for ent-Atorvastatin involves measuring its activation of the pregnane X receptor (PXR). Reporter gene assays are performed using cells transfected with PXR and a luciferase reporter gene. Varying concentrations of ent-Atorvastatin are incubated with the cells, and luciferase activity is measured. The EC50 for PXR activation is determined from dose-response curves. ent-Atorvastatin shows an EC50 of 12.4 μM for luciferase activity.
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| Cell Assay |
In vitro cellular assays for ent-Atorvastatin involve treating primary rat hepatocytes or other PXR-expressing cell lines with varying concentrations of the compound. CYP2B and CYP3A mRNA levels are measured by qRT-PCR to assess PXR activation. Antifungal activity is assessed in Candida albicans cultures by measuring ergosterol levels. The compound's effects on gene expression and fungal viability are compared to controls.
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| Animal Protocol |
In vivo animal experiments for ent-Atorvastatin typically use rat models to study its effects on drug-metabolizing enzymes. Freshly isolated hepatocytes from rat livers are placed into primary culture and treated with ent-Atorvastatin. CYP450 enzyme expression and activity are measured to assess PXR-mediated induction. The compound's lack of HMG-CoA reductase inhibitory activity is confirmed by measuring cholesterol synthesis in treated animals.
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| ADME/Pharmacokinetics |
ent-Atorvastatin is the inactive enantiomer of atorvastatin and does not exhibit the cholesterol-lowering pharmacokinetic profile of the active drug. As a small molecule with molecular weight of 558.64 (C33H35FN2O5), it is expected to have similar absorption and distribution properties to atorvastatin. The compound is metabolized by cytochrome P450 enzymes and has a half-life comparable to atorvastatin. Specific PK parameters are derived from atorvastatin pharmacology.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation It is generally believed that women taking statins should not breastfeed due to concerns about disrupting the infant's lipid metabolism. However, some argue that children with homozygous familial hypercholesterolemia receiving statin treatment from age 1 have lower oral bioavailability and therefore pose a lower risk to breastfed infants, especially rosuvastatin and pravastatin. Some evidence suggests that atorvastatin use by breastfeeding mothers does not cause significant developmental problems in infants. Until more data are available, especially when breastfeeding newborns or premature infants, alternative medications may be preferred. ◉ Impact on Breastfed Infants In a case series of patients with homozygous familial hypercholesterolemia, 6 patients breastfed a total of 11 infants after restarting statin treatment postpartum. The specific statin drugs used by these women were not reported, but most women receiving statin treatment took atorvastatin at a daily dose of 40 or 80 mg. All offspring had normal early development. All children started school at the appropriate age, and no learning difficulties were reported. ◉ Effects on lactation and breast milk Gynecomastia has been reported in men taking atorvastatin. In one case, serum prolactin levels were normal. In another case, suspected rosuvastatin-induced gynecomastia resolved after the patient switched to atorvastatin. ent-Atorvastatin is an inactive enantiomer and is not used as a therapeutic agent. Its safety profile is derived from studies of the atorvastatin enantiomers. As a PXR activator, it may induce drug-metabolizing enzymes and affect the metabolism of co-administered drugs. The compound does not produce the cholesterol-lowering effects or associated toxicities of active atorvastatin. Complete toxicology data are available from atorvastatin development programs. |
| References |
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| Additional Infomation |
ent-Atorvastatin (CAS#: 501121-34-2) is the inactive (3S,5S) enantiomer of atorvastatin, a blockbuster statin drug. Unlike the active (3R,5R) enantiomer, ent-Atorvastatin lacks HMG-CoA reductase inhibitory activity but activates the pregnane X receptor (PXR). It increases CYP2B and CYP3A mRNA levels and exhibits antifungal properties against Candida albicans. ent-Atorvastatin is not approved for clinical use and is primarily used as a research tool.
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| Molecular Formula |
C33H35FN2O5
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| Molecular Weight |
558.65
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| Exact Mass |
558.253
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| CAS # |
501121-34-2
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| Related CAS # |
Atorvastatin;134523-00-5;Atorvastatin-d5 hemicalcium;222412-82-0;(3S,5S)-Atorvastatin sodium salt;1428118-38-0;(rel)-Atorvastatin;110862-48-1;Atorvastatin hemicalcium trihydrate;344920-08-7
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| PubChem CID |
62976
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| Appearance |
Off-white to light yellow solid powder
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| Melting Point |
182-184ºC
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| LogP |
6.386
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
41
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| Complexity |
822
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)C1=C(C(=C(N1CC[C@@H](C[C@@H](CC(=O)O)O)O)C2=CC=C(C=C2)F)C3=CC=CC=C3)C(=O)NC4=CC=CC=C4
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| InChi Key |
XUKUURHRXDUEBC-SVBPBHIXSA-N
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| InChi Code |
InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m0/s1
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| Chemical Name |
(3S,5S)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
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| Synonyms |
3S,5S-Atorvastatin, Atorvastatin calcium trihydrate impurity E, ent-Atorvastatin
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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 |
| 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 : ~125 mg/mL (~223.76 mM)
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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 | 1.7900 mL | 8.9501 mL | 17.9003 mL | |
| 5 mM | 0.3580 mL | 1.7900 mL | 3.5801 mL | |
| 10 mM | 0.1790 mL | 0.8950 mL | 1.7900 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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