| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 10mg |
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| Other Sizes |
| Targets |
HMG-CoA reductase (competitive inhibitor); the ortho-hydroxy metabolite accounts for part of the plasma HMG-CoA reductase inhibitory activity.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
Ortho-hydroxy atorvastatin lactone is an active metabolite of atorvastatin and a potent inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Approximately 70% of the total plasma HMG-CoA reductase inhibitory activity is explained by the active metabolites of atorvastatin. |
| ln Vivo |
In vivo, ortho-hydroxy atorvastatin is a circulating metabolite formed by CYP3A4. It contributes to the lipid-lowering effect of atorvastatin. The lactone form is less active than the open acid form but can be converted to the active acid in vivo.
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| Enzyme Assay |
HMG-CoA reductase activity is measured using purified enzyme and [¹⁴C]-HMG-CoA. Ortho-hydroxy atorvastatin lactone (0.1–100 nM) is pre-incubated with the enzyme, and mevalonate formation is quantified by radioassay or HPLC.
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| Cell Assay |
In vitro cell experiments use HepG2 hepatocytes treated with ortho-hydroxy atorvastatin lactone-d5 (0.01–10 μM). Cholesterol synthesis is measured by [¹⁴C]-acetate incorporation, and HMG-CoA reductase activity in cell lysates is measured.
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| Animal Protocol |
Rodent studies administer atorvastatin or the ortho-hydroxy metabolite by oral gavage at 1–50 mg/kg. Plasma lipids and HMG-CoA reductase activity are measured. Concentrations of atorvastatin and its metabolites are quantified by LC-MS/MS using the d5-labeled internal standard.
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| References |
|
| Molecular Formula |
C33H33N2O5F
|
|---|---|
| Molecular Weight |
556.62392
|
| Exact Mass |
561.269
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| CAS # |
265989-50-2
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| Related CAS # |
2-Hydroxy atorvastatin lactone;163217-74-1
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| PubChem CID |
10816722
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
6.883
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
41
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| Complexity |
874
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
OC1CC(=O)OC(CCN2C(C3=CC=C(F)C=C3)=C(C3=C([2H])C([2H])=C([2H])C([2H])=C3[2H])C(/C(/O)=N/C3=C(O)C=CC=C3)=C2C(C)C)C1
|
| InChi Key |
MNECBMZJZFGTIK-AABVQTEKSA-N
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| InChi Code |
InChI=1S/C33H33FN2O5/c1-20(2)31-30(33(40)35-26-10-6-7-11-27(26)38)29(21-8-4-3-5-9-21)32(22-12-14-23(34)15-13-22)36(31)17-16-25-18-24(37)19-28(39)41-25/h3-15,20,24-25,37-38H,16-19H2,1-2H3,(H,35,40)/t24-,25-/m1/s1/i3D,4D,5D,8D,9D
|
| Chemical Name |
5-(4-fluorophenyl)-1-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-N-(2-hydroxyphenyl)-4-(2,3,4,5,6-pentadeuteriophenyl)-2-propan-2-ylpyrrole-3-carboxamide
|
| 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) |
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 | 1.7966 mL | 8.9828 mL | 17.9656 mL | |
| 5 mM | 0.3593 mL | 1.7966 mL | 3.5931 mL | |
| 10 mM | 0.1797 mL | 0.8983 mL | 1.7966 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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