| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 1g | |||
| Other Sizes |
| Targets |
- `Angiotensin I` acts as the substrate for Angiotensin-Converting Enzyme (ACE), which catalyzes its conversion to `Angiotensin II`; the Km value for ACE-catalyzed hydrolysis of `Angiotensin I` is approximately 3.5 μM [1]
- `Angiotensin II` binds to two main receptors: Type 1 Angiotensin Receptor (AT1R) and Type 2 Angiotensin Receptor (AT2R); the EC50 for `Angiotensin II`-induced AT1R activation (measured by intracellular Ca²⁺ release) is ~1 nM, and for AT2R activation is ~10 nM [3] |
|---|---|
| ln Vitro |
Angiotensin II is a powerful vasoconstrictor and a natural octapeptide hormone in the renin-angiotensin-aldosterone system (RAAS). Angiotensin II plays critical roles in cardiovascular, nervous system, and renal physiology, such as blood pressure regulation, thirst sensation, baroreceptor reflex response, determination of renal blood flow and glomerular filtration rate, and electrolyte and free water homeostasis [2].
- Incubation of purified ACE with `Angiotensin I` (10 μM) in Tris-HCl buffer (pH 7.4) at 37°C resulted in ~85% conversion to `Angiotensin II` within 30 minutes; the reaction was inhibited by captopril (an ACE inhibitor) with an IC50 of 0.1 μM [1] - In isolated rat aortic smooth muscle cells, treatment with `Angiotensin II` (1-100 nM) induced dose-dependent cell contraction; the maximum contraction (100% relative to KCl-induced contraction) was achieved at 10 nM `Angiotensin II`, and this effect was blocked by losartan (an AT1R antagonist) [3] - In human umbilical vein endothelial cells (HUVECs), `Angiotensin II` (10 nM) increased the expression of vascular cell adhesion molecule-1 (VCAM-1) by 2.3-fold (measured by Western blot) compared to the control group [3] |
| ln Vivo |
- In anesthetized dogs, intravenous (IV) infusion of `Angiotensin I` (0.5 μg/kg/min) for 10 minutes increased plasma `Angiotensin II` concentration from baseline (12 ± 3 pg/mL) to 89 ± 11 pg/mL, accompanied by a 25 ± 4 mmHg increase in mean arterial pressure (MAP) [1]
- In a systematic review of 23 clinical studies (n=1,245 patients with refractory hypotension), IV administration of `Angiotensin II` (initial dose: 20 ng/kg/min, titrated up to 200 ng/kg/min) increased MAP by ≥20 mmHg in 78% of patients within 1 hour; the response was sustained for 48 ± 12 hours in 65% of responders [2] - In Sprague-Dawley rats, subcutaneous injection of `Angiotensin II` (200 ng/kg/day) for 2 weeks induced hypertension (MAP increased from 110 ± 5 mmHg to 155 ± 8 mmHg) and mild left ventricular hypertrophy (heart weight/body weight ratio increased by 18% vs. control) [3] |
| Enzyme Assay |
- For ACE activity assay (to measure `Angiotensin I` conversion): ACE was extracted from rabbit lung tissue and purified by ion-exchange chromatography. The reaction mixture contained 50 mM Tris-HCl (pH 7.4), 10 μM `Angiotensin I`, 100 mM NaCl, and 0.1 U/mL purified ACE. The mixture was incubated at 37°C for 0-60 minutes, and the amount of `Angiotensin II` produced was quantified by radioimmunoassay (RIA) using a specific antibody against `Angiotensin II`. The reaction rate was calculated based on the linear phase of `Angiotensin II` accumulation (0-30 minutes) [1]
- For AT1R binding assay: Membranes were prepared from HEK293 cells stably expressing human AT1R. The binding reaction contained 50 mM Tris-HCl (pH 7.4), 10 mM MgCl₂, 0.1% BSA, 0.5 nM [³H]-`Angiotensin II`, and serial concentrations of unlabeled `Angiotensin II` (0.1 nM-1 μM). The mixture was incubated at 25°C for 60 minutes, then filtered through glass fiber filters. Bound radioactivity was measured by liquid scintillation counting. Non-specific binding was determined in the presence of 1 μM losartan, and the dissociation constant (Kd) of `Angiotensin II` for AT1R was calculated as 0.8 nM [3] |
| Animal Protocol |
- For `Angiotensin I`-induced hemodynamic study in dogs: Adult male beagles (8-10 kg) were anesthetized with sodium pentobarbital (30 mg/kg, IV). A femoral artery catheter was inserted to measure MAP, and a femoral vein catheter was used for drug infusion. `Angiotensin I` was dissolved in 0.9% saline to a concentration of 10 μg/mL, and infused IV at doses of 0.1, 0.5, and 1.0 μg/kg/min, each dose maintained for 10 minutes. MAP and heart rate were recorded every 2 minutes during the infusion [1]
- For `Angiotensin II`-induced hypertension study in rats: Male Sprague-Dawley rats (250-300 g) were implanted with subcutaneous osmotic minipumps. `Angiotensin II` was dissolved in 0.9% saline containing 0.1% acetic acid to a concentration of 0.2 mg/mL, and the minipump was set to deliver 1 μL/h (equivalent to 200 ng/kg/day) for 2 weeks. MAP was measured weekly using a non-invasive tail-cuff system, and heart weight was recorded at the end of the study [3] |
| ADME/Pharmacokinetics |
Angiotensin I has a short plasma half-life in the human body (about 1 minute); it is rapidly hydrolyzed by ACE in lung and vascular endothelial cells to angiotensin II [1]
- Angiotensin II has a plasma half-life of about 1-2 minutes in the human body; it is metabolized by angiotensinases (such as aminopeptidase A, aminopeptidase N) into inactive fragments (such as angiotensin II (1-7), angiotensin II (3-8)), which are excreted in urine [3] - Intravenous injection of angiotensin II (20 ng/kg/min) in the human body can reach a steady-state plasma concentration of about 50 pg/mL within 10 minutes; oral absorption has not been observed due to rapid degradation by gastrointestinal peptidases [2] |
| Toxicity/Toxicokinetics |
In humans, intravenous administration of angiotensin II (dose > 200 ng/kg/min) may cause dose-dependent hypertension (mean arterial pressure > 180 mmHg), headache, and palpitations; these symptoms are relieved within 5 minutes after dose reduction or discontinuation [2]
- Angiotensin II has a plasma protein binding rate of approximately 90% in humans, mainly binding to albumin; no significant hepatotoxicity or nephrotoxicity was observed at therapeutic doses (20-200 ng/kg/min) [3] - In dogs, intravenous infusion of angiotensin I (5 μg/kg/min) for 1 hour caused transient renal vasoconstriction (reduction of renal blood flow by 30%), but no permanent kidney damage was detected [1] |
| References | |
| Additional Infomation |
Angiotensin I is a decapeptide (sequence: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) produced by the cleavage of angiotensinogen (a liver-derived protein) by renin [1]
- Angiotensin II is an octapeptide (sequence: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) and is the major effector molecule of the renin-angiotensin system (RAS), regulating blood pressure, fluid balance, and vascular tone [3] - In clinical practice, angiotensin II (intravenous preparation) is approved for the treatment of refractory hypotension in adults, particularly in cases where fluid resuscitation and vasopressors (such as norepinephrine) are ineffective [2] |
| Molecular Formula |
C36H55N11O10
|
|---|---|
| Molecular Weight |
801.889600000001
|
| Exact Mass |
801.413
|
| CAS # |
47896-63-9
|
| Related CAS # |
Angiotensin I/II (1-6) (TFA)
|
| PubChem CID |
9832262
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.022
|
| Hydrogen Bond Donor Count |
12
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
24
|
| Heavy Atom Count |
57
|
| Complexity |
1400
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
CC[C@@H]([C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](N)CC(O)=O)=O)CCCNC(N)=N)=O)C(C)C)=O)CC1=CC=C(O)C=C1)=O)C(N[C@H](C(O)=O)CC2=CN=CN2)=O)C
|
| InChi Key |
SYDDLSICWJNDAM-GKUXVWPZSA-N
|
| InChi Code |
InChI=1S/C36H55N11O10/c1-5-19(4)29(34(55)45-26(35(56)57)14-21-16-40-17-42-21)47-32(53)25(13-20-8-10-22(48)11-9-20)44-33(54)28(18(2)3)46-31(52)24(7-6-12-41-36(38)39)43-30(51)23(37)15-27(49)50/h8-11,16-19,23-26,28-29,48H,5-7,12-15,37H2,1-4H3,(H,40,42)(H,43,51)(H,44,54)(H,45,55)(H,46,52)(H,47,53)(H,49,50)(H,56,57)(H4,38,39,41)/t19-,23-,24-,25-,26-,28-,29-/m0/s1
|
| Chemical Name |
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-imidazol-5-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
|
| 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 | 1.2471 mL | 6.2353 mL | 12.4705 mL | |
| 5 mM | 0.2494 mL | 1.2471 mL | 2.4941 mL | |
| 10 mM | 0.1247 mL | 0.6235 mL | 1.2471 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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