| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Tezosentan targets the endothelin A (ETA) and endothelin B (ETB) receptors. Endothelin-1 is a potent vasoconstrictor peptide that acts through these receptors to regulate vascular tone. By blocking both ETA and ETB receptors, Tezosentan inhibits endothelin-1-mediated vasoconstriction, leading to vasodilation and reduced vascular resistance. The compound is a dual endothelin receptor antagonist with high affinity for both receptor subtypes.
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| ln Vitro |
Tezosentan's ET receptor affinity was assessed in a variety of cell types and tissues. The selective binding of 125I-labeled ET-1 to ETA receptors is inhibited by tesosentan, with an inhibitory potency (Ki) of 18 nM on insect cell membranes infected with baculovirus and 0.3 nM on CHO cells. Similarly, tezosentan has an inhibitory affinity of 10 to 21 nM for the specific binding of 125I-labeled ET-1, ET-3, or sarafotoxin S6c to the ETB receptor. Tezosentan did not show any binding inhibitory activity at doses up to 1 μM in 27 radioligand binding experiments that varied with ET binding. Less than 20% mild inhibition of H1 centers, serotonin 2A, and vasopressin V1 receptors is produced by tezosentan (1 μM) [1].
In vitro, Tezosentan demonstrates potent antagonistic activity at both ETA and ETB receptors. As a dual endothelin receptor antagonist, it blocks endothelin-1-induced vasoconstriction in isolated blood vessel preparations. Specific IC50 values for receptor binding or functional inhibition are not detailed in the available sources. The compound's activity has been characterized in receptor binding and functional assays using cell lines expressing ETA and ETB receptors. |
| ln Vivo |
In Wistar rats, the pressor effects of massive ET-1 were dose-dependently reduced by tesosentan (P<0.001 at all doses). At the lowest studied dose of 1 mg/kg, tezosentan reduced the pressor effects of different doses of big ET-1 by 50% to 80%. In these rats, tezosentan by itself had no effect on blood pressure. In rat models of acute renal failure, tezosentan exhibits remarkable efficacy. In rats with acute renal ischemia, ET antagonists have been demonstrated to prevent vasoconstriction and renal failure [1].
Tezosentan has been evaluated in clinical trials for the treatment of acute heart failure and pulmonary arterial hypertension. As a potent vasodilator, it reduces pulmonary and systemic vascular resistance, improving hemodynamics in patients with heart failure. However, clinical development was discontinued due to lack of efficacy in phase III trials. The compound is used in research on endothelin signaling and cardiovascular diseases. |
| Enzyme Assay |
The endothelin receptor binding assay for Tezosentan involves incubating the compound with membrane preparations from cells expressing human ETA or ETB receptors and a radiolabeled endothelin-1 ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 for displacement of the radioligand is calculated from the competition curve. Functional antagonism is assessed using calcium mobilization assays in cells expressing endothelin receptors.
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| Cell Assay |
To evaluate the cellular activity of Tezosentan, cells expressing ETA or ETB receptors are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with varying concentrations of Tezosentan and then stimulated with endothelin-1. The intracellular calcium flux is measured using a fluorescence plate reader. The IC50 for inhibition of endothelin-1-induced calcium flux is calculated.
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| Animal Protocol |
The in vivo efficacy of Tezosentan is evaluated in animal models of heart failure and pulmonary hypertension. Rats or dogs with induced heart failure or pulmonary hypertension are treated with Tezosentan intravenously at various doses. Hemodynamic parameters such as cardiac output, pulmonary artery pressure, and systemic vascular resistance are measured. The compound's ability to improve hemodynamics and reduce vascular resistance is assessed.
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| ADME/Pharmacokinetics |
Biological Half-Life
The drug undergoes a distinct and rapid disposal phase (half-life of 6 minutes) during elimination, which constitutes the majority of the elimination process; this is followed by a slower disposal phase (half-life of 3 hours), likely due to the distribution of the drug from tissues. Tezosentan is administered intravenously and has a pharmacokinetic profile characterized by rapid onset and moderate half-life. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 582.67 and a molecular formula of C28H34N6O6S. It is typically stored as a powder at -20°C. |
| Toxicity/Toxicokinetics |
Specific toxicity data for Tezosentan are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a dual endothelin receptor antagonist, and its toxicity profile has been evaluated in preclinical and clinical studies. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Tinzosentan is an intravenously administered endothelin receptor A/B antagonist. Originally developed as a vasodilator for the treatment of acute heart failure, studies have shown it to be ineffective in treating dyspnea or preventing cardiovascular events.
Drug Indications It has been investigated for the treatment of congestive heart failure, liver disease, and heart disease. Tezosentan is a dual endothelin receptor antagonist targeting both ETA and ETB receptors. It was developed for the treatment of acute heart failure and pulmonary arterial hypertension. It acts as a potent vasodilator by blocking the effects of endothelin-1. Clinical development was discontinued due to lack of efficacy in phase III trials. The compound is used in research on endothelin signaling and cardiovascular diseases. |
| Molecular Formula |
C27H27N9O6S
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|---|---|
| Molecular Weight |
605.62498
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| Exact Mass |
605.18
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| CAS # |
180384-57-0
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| PubChem CID |
151174
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| Appearance |
Off-white to gray solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
761.2±70.0 °C at 760 mmHg
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| Flash Point |
414.2±35.7 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.634
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| LogP |
0.89
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
43
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| Complexity |
962
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
TUYWTLTWNJOZNY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H27N9O6S/c1-16(2)18-8-9-22(29-15-18)43(38,39)34-26-23(42-21-7-5-4-6-20(21)40-3)27(41-13-12-37)31-24(30-26)17-10-11-28-19(14-17)25-32-35-36-33-25/h4-11,14-16,37H,12-13H2,1-3H3,(H,30,31,34)(H,32,33,35,36)
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| Chemical Name |
N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide
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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 : ~50 mg/mL (~82.56 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 | 1.6512 mL | 8.2559 mL | 16.5117 mL | |
| 5 mM | 0.3302 mL | 1.6512 mL | 3.3023 mL | |
| 10 mM | 0.1651 mL | 0.8256 mL | 1.6512 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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