| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
ET-RA, ET-RB[1]
Endothelin-3 binds to G-protein-coupled transmembrane endothelin receptors, specifically the ET-B receptor (ETBR, also known as EDNRB) with higher affinity than ET-A receptor (ETAR). ET-3 binds with approximately equal affinity to both ET-B and ET-A in some systems but is generally considered ET-B selective. Activation of these receptors leads to phospholipase C activation, IP3-mediated calcium mobilization, and MAPK/ERK signaling, resulting in vasoconstriction (via ET-A on vascular smooth muscle) and vasodilation (via ET-B on endothelial cells through NO release). ET-3 also plays key roles in neural crest cell migration and differentiation. |
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| ln Vitro |
In vitro, ET-3 attenuates thrombin-evoked aggregation of human platelets and acts as a potent stimulator of interleukin-6 production by endothelial cell lines. It activates phospholipase C in fibroblasts expressing ET-A receptors and induces the production of VEGF (vascular endothelial growth factor). ET-3 also regulates intracellular calcium levels in various cell types and modulates gene expression through receptor-mediated signaling. It is used in receptor-binding studies to delineate ET-A vs. ET-B pharmacology.
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| ln Vivo |
In vivo, ET-3 is a potent vasoconstrictor and vasoactive peptide that regulates blood pressure and vascular tone. It is involved in the development of the enteric nervous system and melanocyte development during embryogenesis. ET-3 also plays roles in cardiovascular and renal physiology and has been implicated in disease states including Hirschsprung disease (congenital megacolon) and Waardenburg syndrome when ET-3 or EDNRB signaling is disrupted. In animal models, ET-3 can induce vasoconstriction in certain vascular beds and influence renal function and water-electrolyte balance.
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| Enzyme Assay |
For receptor-binding assays, express recombinant ET-A or ET-B receptors in HEK293 cells or use membrane preparations from tissues naturally expressing both receptors. Incubate membranes (20-50 ug protein) with 10-100 pM 125I-labeled ET-3 in binding buffer (50 mM Tris-HCl, 0.1% BSA, 10 mM MgCl2, pH 7.4) for 2 hours at 25degC. Add unlabeled ET-3 (1 pM-10 uM) for competition binding. Terminate by filtration through GF/C filters presoaked in 0.3% polyethyleneimine. Wash filters, measure retained radioactivity in gamma counter. Determine IC50 and Ki using nonlinear regression. For selectivity assays, compare binding affinities to ET-A vs. ET-B using ET-1 and ET-3 as competitors and subtype-selective ligands (BQ-123 for ET-A, BQ-788 for ET-B).
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| Cell Assay |
Culture cell lines expressing endothelin receptors (e.g., CHO cells stably transfected with ET-A or ET-B, or primary cell cultures such as vascular smooth muscle cells, endothelial cells, or fibroblasts) in appropriate medium. For calcium mobilization assays, load cells with Fura-2 AM or Fluo-4 AM (2-5 uM) in Hanks' balanced salt solution with 20 mM HEPES for 30-60 minutes at 37degC. Wash, add ET-3 (1 pM-1 uM) to cells, and measure intracellular calcium concentration ([Ca2+]i) by fluorescence ratio (340/380 nm for Fura-2) or fluorescence intensity (Flue-4) using a plate reader or fluorescence microscope. For proliferation studies, treat cells with ET-3 (0.1-100 nM) for 24-72 hours and assess by MTT assay, cell counting, or 3H-thymidine incorporation. For IL-6 production, treat endothelial cell lines with ET-3 (1-100 nM) for 6-24 hours, collect supernatant, and measure IL-6 by ELISA. For ERK activation, treat cells for 0-30 minutes, lyse, and perform Western blot with phospho-ERK1/2 antibodies.
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| Animal Protocol |
For vasoconstriction studies, use isolated mouse or rat mesenteric artery rings (2-3 mm length) mounted in organ bath chambers containing oxygenated (95% O2/5% CO2) Krebs-Henseleit buffer at 37degC. Equilibrate for 60 minutes under 1 g tension. Add 40-60 mM KCl to test vessel viability. After washout, add ET-3 (0.1 pM-100 nM) cumulatively and record isometric tension. For systemic studies, administer ET-3 via intravenous or intra-arterial injection (0.1-10 nmol/kg) in anesthetized rats or mice and monitor mean arterial pressure (MAP) and heart rate. For developmental biology studies, use ET-3 knockout mouse models or EDNRB mutant models (piebald lethal mice) to study neural crest cell migration, enteric nervous system development, and melanocyte development. Administer ET-3 exogenously in embryonic explants or organoid cultures to rescue developmental defects. For pharmacokinetic studies, administer ET-3 via intravenous injection (1-10 ug/kg) and collect blood at multiple time points for measurement by radioimmunoassay (RIA) or ELISA.
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| ADME/Pharmacokinetics |
As a 21-amino acid cyclic peptide (MW approximately 2757 for TFA salt, disulfide-bridged), ET-3 is rapidly cleared from circulation with a plasma half-life of 2-5 minutes in rodents. Clearance occurs primarily via receptor-mediated endocytosis and proteolytic degradation in the lungs, kidneys, and liver. The TFA salt enhances water solubility for in vitro and in vivo applications. ET-3 is not orally bioavailable due to enzymatic degradation. The peptide is stored lyophilized at -20degC, protected from light and moisture, and reconstituted in aqueous buffers (e.g., 0.1% BSA in water or saline) just before use.
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| Toxicity/Toxicokinetics |
Endogenous ET-3 is present at low picomolar levels in plasma and tissues and is tightly regulated. Exogenous administration of pharmacological doses (nmol/kg range) can cause dose-dependent vasoconstriction, hypertension, and organ hypoperfusion. Toxic effects at high doses in animal models include acute hypertension, myocardial ischemia, renal vasoconstriction, and pulmonary edema. The compound is not intended for human use. Material safety data sheets indicate that TFA salts may cause irritation; standard laboratory precautions (gloves, lab coat, safety glasses) should be used. Avoid inhalation, ingestion, and skin contact. The compound is classified as a research chemical only.
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| References | |
| Additional Infomation |
Endothelin-3 TFA salt is also known as Endothelin 3 (Rat,Human) (TFA). The trifluoroacetate counterion enhances solubility and stability during storage. The peptide is conserved across human, mouse, rabbit, and rat species (identical sequence), enabling translational research across species. ET-3 is used in receptor pharmacology, GPCR signaling studies, developmental biology (neural crest, enteric nervous system), cardiovascular physiology, and cancer research (angiogenesis, tumor microenvironment). The compound is for research use only and not for diagnostic or therapeutic applications.
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| Molecular Formula |
C123H169F3N26O35S4
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|---|---|
| Molecular Weight |
2757.07
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| Related CAS # |
Endothelin-3, human, mouse, rabbit, rat;117399-93-6
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| Appearance |
Solid powder
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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, avoid exposure to moisture. |
| 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 | 0.3627 mL | 1.8135 mL | 3.6270 mL | |
| 5 mM | 0.0725 mL | 0.3627 mL | 0.7254 mL | |
| 10 mM | 0.0363 mL | 0.1814 mL | 0.3627 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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