| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
After myocardial infarction, atorvastatin hemicalcium trihydrate treatment reduces myocardial cell apoptosis by downregulating the expression of GRP78, caspase-12, and CHOP in myocardial cells. Additionally, heart failure and angiotensin II (Ang II) stimulation activate the endoplasmic reticulum (ER) stress system[4].
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|---|---|
| ln Vivo |
In ApoE−/− mice triggered by Ang II, atorvastatin (20–30 mg/kg; oral gavage; once daily; for 28 days) hemicadium trihydrate therapy dramatically lowers endoplasmic reticulum (ER) stress signaling proteins, apoptotic cell count, and activation of Caspase12 and Bax. After taking atorvastatin, proinflammatory cytokines like IL-6, IL-8, and IL-1β are all noticeably inhibited[5].
|
| Animal Protocol |
Animal/Disease Models: Forty 8weeks old ApoE−/− mice induced with angiotensin II (Ang II)[5]
Doses: 20 mg/kg, 30 mg/kg Route of Administration: po (oral gavage); one time/day; for 28 days Experimental Results: Dramatically decreased ER stress signaling proteins, the number of apoptotic cells, and the activation of Caspase12 and Bax in the Ang II-induced ApoE−/− mice. Proinflammatory cytokines such as IL-6, IL-8, IL-1β were all remarkably inhibited. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Atorvastatin is primarily metabolized into ortho- and para-hydroxylated derivatives and various β-oxidation products. In vitro studies have shown that the ortho- and para-hydroxylated metabolites have comparable inhibitory effects on HMG-CoA reductase to atorvastatin. Approximately 70% of circulating HMG-CoA reductase inhibitory activity is attributed to the active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Atorvastatin selectively and competitively inhibits the liver enzyme HMG-CoA reductase. Since HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, inhibition of HMG-CoA reductase leads to a decrease in liver cholesterol levels. This decrease in liver cholesterol levels stimulates the upregulation of hepatic LDL-C receptors, thereby increasing hepatic uptake of LDL-C and reducing serum LDL-C concentration. Toxicity Data Overall, the condition was well tolerated. Side effects may include myalgia, constipation, fatigue, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxic reactions in Asian patients, dose reduction should be considered. |
| References | |
| Additional Infomation |
Atorvastatin hemicalcium trihydrate is the trihydrate form of atorvastatin calcium. It is an exogenous substance and an environmental pollutant. It is a hydrate and also a synthetic statin drug. It contains atorvastatin calcium. Atorvastatin calcium is the calcium salt of atorvastatin, a synthetic lipid-lowering drug. Atorvastatin 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 increases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, enhances LDL uptake and catabolism, reduces LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also have direct antitumor activity, possibly through the inhibition of farnesylation and geranylation of proteins such as small GTP-binding proteins, leading to cell cycle arrest in the G1 phase. This drug may also enhance the sensitivity of tumor cells to cell inhibitors by inhibiting Akt phosphorylation in a mTOR-dependent manner. Atorvastatin (Lipitor) belongs to the statin class of drugs and is used to lower cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis in the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin primarily functions in the liver. Lowered liver cholesterol levels increase the liver's absorption of cholesterol, thereby lowering plasma cholesterol levels.
|
| Molecular Weight |
616.733092069626
|
|---|---|
| Exact Mass |
1262.516
|
| CAS # |
344920-08-7
|
| Related CAS # |
Atorvastatin hemicalcium salt;134523-03-8;Atorvastatin;134523-00-5;(3S,5S)-Atorvastatin;501121-34-2;Atorvastatin-d5 hemicalcium;222412-82-0;(rel)-Atorvastatin;110862-48-1
|
| PubChem CID |
168440556
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
12
|
| Hydrogen Bond Acceptor Count |
18
|
| Rotatable Bond Count |
22
|
| Heavy Atom Count |
89
|
| Complexity |
817
|
| Defined Atom Stereocenter Count |
4
|
| 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.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.O.O.O.O.O.O.[Ca+2]
|
| InChi Key |
KQPCBHBPIZWHAS-NGUMWDRNSA-L
|
| InChi Code |
InChI=1S/2C33H35FN2O5.Ca.6H2O/c2*1-21(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;;;;;;;/h2*3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40);;6*1H2/q;;+2;;;;;;/p-2/t2*26-,27-;;;;;;;/m11......./s1
|
| Chemical Name |
calcium;(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate;hexahydrate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 1.6215 mL | 8.1073 mL | 16.2146 mL | |
| 5 mM | 0.3243 mL | 1.6215 mL | 3.2429 mL | |
| 10 mM | 0.1621 mL | 0.8107 mL | 1.6215 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.
Link: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-000575-17
Condition:mixed dyslipidaemiaLink: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007297-38
Condition:acute coronary syndrome without ST segment elevationLink: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2009-010761-22
Condition:Stroke
Title:Effects of periprocedural atorvastatin therapy on patients undergoing percutaneous coronary intervention (PCI)
Status:Completed
Date:2009-04-16
Eudractnumber:2009-010842-67
Link: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2009-010842-67
Condition:candidates patients for percutaneous coronary intervention revascularization on the basis of claims made by the current guidelines in accordance with the criteria of inclusion / exclusion protocolLink: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-004000-13
Condition:Coronary Atheroma -- The current trial will study patients who have a clinical indication for coronary catheterization and who have coronary artery disease.Link: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-005618-38
Condition:Osteoporosis in hypercholesterolemic patientsLink: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-005056-16
Condition:elective PCI in de novo coronaric lesionsLink: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2006-005757-30
Condition:Pts with coronary disease undergoing coronary artery bypass graft surgery.Products are for research use only; We do not sell to patients
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