| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
| Targets |
Angiotensin II Type 1 Receptor (AT1). Valsartan ethyl ester acts as an angiotensin II receptor blocker (ARB) that selectively and competitively blocks AT1 receptors in the renin-angiotensin-aldosterone system (RAAS). This prevents angiotensin II from binding to its receptor, inhibiting vasoconstriction and aldosterone secretion, and ultimately lowering blood pressure.
|
|---|---|
| ln Vitro |
Valsartan ethyl ester binds selectively to the AT1 receptor with an IC50 of approximately 2.6 nM. It is a competitive antagonist that blocks angiotensin II-induced vasoconstriction in isolated rabbit aorta strips (pA2 = 8.2-8.5). Unlike some other ARBs, it does not exhibit partial agonist activity or significant affinity for other receptor subtypes.
|
| ln Vivo |
In renin-dependent hypertensive rat models, intravenous administration of valsartan (1-30 mg/kg) produces dose-dependent reductions in mean arterial blood pressure (MAP) of up to 30 mmHg. Oral administration (3-30 mg/kg) in conscious spontaneously hypertensive rats (SHR) also demonstrates dose-dependent antihypertensive effects lasting 12-24 hours, with an ED30 (dose producing 30 mmHg reduction) of approximately 10 mg/kg.
|
| Enzyme Assay |
Standard radioligand binding assays are conducted using membrane preparations from CHO cells stably expressing human AT1 receptors. Membranes (~50 microg protein) are incubated with [¹2⁵I]-Sar¹-Ile⁸-angiotensin II as the radioligand and varying concentrations of valsartan ethyl ester for 60-90 minutes at 25degC in Tris-HCl buffer (pH 7.4). Bound and free ligands are separated by rapid filtration through glass fiber filters, and bound radioactivity is counted with a gamma counter. IC50 values are calculated using nonlinear regression.
|
| Cell Assay |
Angiotensin II (10-¹⁰ to 10-⁶ M) is added to isolated rabbit aortic rings mounted in organ baths containing Krebs-Henseleit buffer at 37degC, and the contractile response is recorded. Tissues are pre-incubated with varying concentrations of valsartan ethyl ester for 30 minutes before angiotensin II addition. The pA2 value is determined by Schild plot analysis of rightward shifts in the concentration-response curve, representing the competitive antagonist potency at AT1 receptors.
|
| Animal Protocol |
Male spontaneously hypertensive rats (SHR; 250-300 g) are used. Animals are fasted overnight and orally dosed with valsartan ethyl ester (1-30 mg/kg) or vehicle. A catheter is implanted into the carotid artery for continuous blood pressure monitoring. Mean arterial pressure (MAP) and heart rate are recorded pre-dose and for 24 hours post-dose using a digital pressure transducer. The maximal reduction in MAP and the duration of action are calculated.
|
| ADME/Pharmacokinetics |
Valsartan ethyl ester is an ester prodrug that is rapidly hydrolyzed to its active acid form, valsartan, in vivo. It exhibits improved lipophilicity and may show different absorption and distribution properties compared to valsartan. Valsartan itself has an oral bioavailability of ~25%, is 95% serum protein bound, and has a terminal half-life of ~6 hours. It is primarily excreted unchanged in feces (70%) and urine (30%).
|
| Toxicity/Toxicokinetics |
Valsartan has an excellent safety profile. Common adverse effects include dizziness, headache, hypotension, and hyperkalemia. Rare but serious effects include angioedema and renal impairment. The ethyl ester derivative is not intended for human therapeutic use but may exhibit similar toxicity at high doses due to hydrolysis to valsartan.
|
| References | |
| Additional Infomation |
Valsartan was approved by the FDA in 1996 for hypertension and later for heart failure (2002) and post-myocardial infarction (2003). It is available as Diovan® and in combination products (e.g., Entresto® with sacubitril for heart failure). The ethyl ester impurity is a key reference standard for API quality control, ensuring the safety and efficacy of valsartan drug products in pharmaceutical manufacturing.
|
| Molecular Formula |
C26H33N5O3
|
|---|---|
| Molecular Weight |
463.572
|
| Exact Mass |
463.258
|
| CAS # |
1111177-30-0
|
| PubChem CID |
58153804
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
655.7±65.0 °C at 760 mmHg
|
| Flash Point |
350.4±34.3 °C
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.562
|
| LogP |
5.83
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
34
|
| Complexity |
638
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CCCCC(=O)N(CC1=CC=C(C=C1)C2=CC=CC=C2C3=NNN=N3)[C@@H](C(C)C)C(=O)OCC
|
| InChi Key |
BTSNVLAJCYDJEU-DEOSSOPVSA-N
|
| InChi Code |
InChI=1S/C26H33N5O3/c1-5-7-12-23(32)31(24(18(3)4)26(33)34-6-2)17-19-13-15-20(16-14-19)21-10-8-9-11-22(21)25-27-29-30-28-25/h8-11,13-16,18,24H,5-7,12,17H2,1-4H3,(H,27,28,29,30)/t24-/m0/s1
|
| Chemical Name |
ethyl (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoate
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~250 mg/mL (~539.29 mM)
|
|---|---|
| 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 | 2.1572 mL | 10.7859 mL | 21.5717 mL | |
| 5 mM | 0.4314 mL | 2.1572 mL | 4.3143 mL | |
| 10 mM | 0.2157 mL | 1.0786 mL | 2.1572 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
