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| Targets |
Endothelin-3 binds to G-protein-linked transmembrane receptors, specifically ET-RA and ET-RB. It shows selectivity for the ET-B receptor subtype over ET-A. ET-B receptor activation mediates vasodilation (via NO release from endothelial cells) and vasoconstriction (via smooth muscle contraction), as well as other effects including cell proliferation, migration, and adhesion. Endothelin-3 at low concentrations may attenuate inflammatory responses via ETB2 activation and NO production.
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| ln Vitro |
The vasoconstrictor peptide family Endothelin (ET) has three distinct isomers: ET-1, ET2, and ET-3. It is composed of 21 amino acids. Vascular smooth muscle cells (VSMC), the heart, brain, and plasma all contain endothelin-3. Large Endothelin-3 is broken down by VSMC surface enzymes into the equivalent mature peptide Endothelin-3. In coronary VSMCs, endothelin-3 suppresses the production of endothelin ETA receptors without altering receptor density or functional ETA receptor responses. On the other hand, the vasoconstrictive response of the ETB receptor is abolished at high concentrations of Endothelin-3 (100 nM) owing to the desensitizing impact of Endothelin-3 [1]. ENCC adherence to different ECM components is stimulated by endothelin-3. Endothelin-3 causes quick modifications to the protrusion dynamics and morphology of ENCCs, which promotes lamellipodia growth and stabilization. This process is in line with an increase in focal adhesions and activated β1-integrin [2].
Endothelin-3 is a 21-amino acid vasoactive peptide that binds to G-protein-linked transmembrane receptors ET-RA and ET-RB. It is an endogenous ligand of the endothelin receptor family. Endothelin-3 shows selectivity for the ET-B receptor subtype. The peptide is involved in vascular contraction, blood pressure regulation, and other physiological processes. Endothelin-3 differs from endothelin-1 in six amino acids. At low concentrations, it may attenuate inflammatory responses via ETB2 activation and NO production. |
| ln Vivo |
Endothelin-3 at low doses may reduce inflammatory reactions by producing NO and activating ETB2. At low doses, endothelin 3, which primarily works on ETB, particularly prevents platelet-activating factor (PAF)-induced paw edema, but endothelin 2, which acts on ETA and ETB, and ET-1 do not exhibit any inhibitory activity. The levels of inhibition exhibited by ET-1 and Endothelin-3 (0.5 pmol/paw) were found to be similar to those of Endothelin-3 (0.5 pmol/paw) when BQ-123 was present (66.4 ± 6.7% and 65.4 ± 22.6%, respectively). paw) by itself (65.4 ± 10.9%), whereas in the presence of BQ-788, neither ET-1 nor endothelin-3 exhibited inhibitory action [3].
In vivo, Endothelin-3 increases blood pressure in spontaneously hypertensive and normotensive rats. It promotes migration and adhesion of enteric neural crest cells (ENCCs) to the embryonic gut in mice via interaction with ETB. The peptide is involved in vascular contraction and blood pressure regulation. Its effects are mediated through ET-RA and ET-RB receptor activation. Endothelin-3 plays important roles in development, cardiovascular function, and inflammation. |
| Enzyme Assay |
In vitro receptor binding assays are performed using membrane preparations from cells expressing ET-A or ET-B receptors. Increasing concentrations of Endothelin-3 (0.01 nM - 1 μM) are incubated with a fixed concentration of radiolabeled endothelin-1 (e.g., [¹²⁵I]-ET-1) in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl₂, 0.1% BSA) for 60-120 minutes at room temperature. Nonspecific binding is determined using 1 μM unlabeled ET-1. Bound radioactivity is separated by filtration and quantified. IC50 or Ki values are calculated. ET-B selectivity can be assessed by comparing binding affinities at ET-A vs. ET-B receptors.
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| Cell Assay |
Cellular assays for Endothelin-3 include measurement of receptor activation and downstream signaling. Cells expressing ET-A or ET-B receptors are treated with varying concentrations of Endothelin-3 (0.01 nM - 1 μM). Receptor activation is measured by detecting intracellular calcium mobilization using fluorescent calcium indicators (e.g., Fluo-4 AM). For ET-B-mediated NO production, endothelial cells are treated with Endothelin-3 and NO levels are measured using the Griess assay or DAF-FM fluorescence. Cell migration and adhesion assays can be performed using ENCCs or other relevant cell types.
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| Animal Protocol |
In animal studies, Endothelin-3 is typically administered via intravenous injection to rodents. For blood pressure studies, rats (normotensive or spontaneously hypertensive) are anesthetized and catheterized for blood pressure monitoring. Endothelin-3 is injected intravenously at varying doses (0.1-10 nmol/kg), and blood pressure changes are recorded. For developmental studies, mice are used to study ENCC migration to the embryonic gut. Endothelin-3 is administered or studied in knockout models to assess its role in development. Endpoints include blood pressure, heart rate, tissue histology, and ENCC migration.
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| ADME/Pharmacokinetics |
Endothelin-3 is a 21-amino acid peptide with a molecular weight of 2643.05 and formula C121H168N26O33S4. As a peptide, it is susceptible to proteolytic degradation in vivo, which limits its half-life. The compound should be stored as powder at -20°C. It is soluble in aqueous buffers. For in vivo administration, solutions should be prepared fresh and used immediately. The peptide is stable when stored under appropriate conditions. Further pharmacokinetic studies including plasma half-life, clearance, and tissue distribution would be valuable for in vivo applications.
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| Toxicity/Toxicokinetics |
No specific toxicity data are documented for Endothelin-3. As an endogenous peptide, it is naturally produced in the body and plays important physiological roles at appropriate concentrations. However, excessive endothelin signaling has been implicated in pathological conditions including hypertension, heart failure, and pulmonary arterial hypertension. In research settings, standard laboratory safety practices should be followed when handling the peptide. The compound is intended for research use only and is not approved for human therapeutic applications.
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| References |
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| Additional Infomation |
Endothelin-3 (human, mouse, rabbit, rat) is a 21-amino acid vasoactive peptide with high conservation across species. It is a member of the endothelin peptide family, which includes endothelin-1, endothelin-2, and endothelin-3. Endothelin-3 shows selectivity for the ET-B receptor subtype. The peptide is involved in vascular contraction, blood pressure regulation, development (neural crest cell migration), and inflammation. It is commonly used in cardiovascular and developmental biology research. The compound is for research use only.
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| Molecular Formula |
C₁₂₁H₁₆₈N₂₆O₃₃S₄
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| Molecular Weight |
2643.04
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| Exact Mass |
2641.11
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| CAS # |
117399-93-6
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| Related CAS # |
Endothelin-3, human, mouse, rabbit, rat TFA
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| PubChem CID |
16180095
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.339
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| Hydrogen Bond Donor Count |
34
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| Hydrogen Bond Acceptor Count |
41
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| Rotatable Bond Count |
49
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| Heavy Atom Count |
184
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| Complexity |
5720
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| Defined Atom Stereocenter Count |
25
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| SMILES |
CC[C@@H]([C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]1CSSC[C@H](N)C(N[C@H](C(N[C@H]2CSSC[C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC2=O)CC3=CC=CC=C3)=O)[C@H](O)C)=O)CC4=CC=C(O)C=C4)=O)CCCCN)=O)CC(O)=O)=O)CCCCN)=O)CCC(O)=O)=O)C(N[C@H](C(N[C@H](C(N[C@H](C(N1)=O)CC5=CC=C(O)C=C5)=O)CC6=CC=C(O)C=C6)=O)C(C)C)=O)=O)[C@H](O)C)=O)=O)CC7=CN=CN7)=O)CC(C)C)=O)CC(O)=O)=O)[C@H](CC)C)=O)C(N[C@H](C(O)=O)CC8=CNC9=CC=CC=C89)=O)C
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| InChi Key |
OQGZWNZGVYLIFX-JQWUVQPESA-N
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| InChi Code |
InChI=1S/C121H168N26O33S4/c1-11-62(7)97(117(175)139-89(121(179)180)49-70-53-126-77-25-17-16-24-75(70)77)145-118(176)98(63(8)12-2)144-112(170)88(52-95(157)158)136-105(163)81(44-60(3)4)131-109(167)86(50-71-54-125-59-127-71)134-113(171)90-56-182-181-55-76(124)101(159)146-99(64(9)148)120(178)142-91-57-183-184-58-92(115(173)143-96(61(5)6)116(174)137-84(48-69-32-38-74(152)39-33-69)107(165)132-82(108(166)141-90)46-67-28-34-72(150)35-29-67)140-104(162)80(40-41-93(153)154)130-102(160)78(26-18-20-42-122)129-110(168)87(51-94(155)156)135-103(161)79(27-19-21-43-123)128-106(164)83(47-68-30-36-73(151)37-31-68)138-119(177)100(65(10)149)147-111(169)85(133-114(91)172)45-66-22-14-13-15-23-66/h13-17,22-25,28-39,53-54,59-65,76,78-92,96-100,126,148-152H,11-12,18-21,26-27,40-52,55-58,122-124H2,1-10H3,(H,125,127)(H,128,164)(H,129,168)(H,130,160)(H,131,167)(H,132,165)(H,133,172)(H,134,171)(H,135,161)(H,136,163)(H,137,174)(H,138,177)(H,139,175)(H,140,162)(H,141,166)(H,142,178)(H,143,173)(H,144,170)(H,145,176)(H,146,159)(H,147,169)(H,153,154)(H,155,156)(H,157,158)(H,179,180)/t62-,63-,64+,65+,76-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,96-,97-,98-,99-,100-/m0/s1
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| Chemical Name |
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1R,4S,7S,10S,13S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S)-31-amino-7,13-bis(4-aminobutyl)-22-benzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-19,28-bis[(1R)-1-hydroxyethyl]-16,39,42-tris[(4-hydroxyphenyl)methyl]-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
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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 |
| 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 | 0.3784 mL | 1.8918 mL | 3.7835 mL | |
| 5 mM | 0.0757 mL | 0.3784 mL | 0.7567 mL | |
| 10 mM | 0.0378 mL | 0.1892 mL | 0.3784 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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