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Purity: ≥98%
Phosphoramidon disodium salt is a potent metalloendopeptidase inhibitor, which is widely used as a biochemical research tool. Phosphoramidon In porcine aortic endothelial cells, phosphoramidon (10-4 M) inhibited immunoreactive-endothelin (IR-ET) release by 10-20% and increased IR-CTF levels. These results suggested that phosphoramidon reduced the IR-ET release through affecting the conversion of big ET-1 to ET-l. In cultured endothelial cells, phosphoramidon inhibited the increase of ET-1 and C-terminal fragment (CTF) of big ET-1. However, phosphoramidon increased big ET-1 secretion
| Targets |
Phosphoramidon inhibits Endothelin-Converting Enzyme (ECE) with an IC50 of 3.5 µM [3].
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| ln Vitro |
In solubilized rabbit lung membranes, phosphoramidon (1-500 μM; 30 min) suppresses ET-converting enzyme (ECE) activity in a dose-dependent manner[5].
In a rabbit lung membrane preparation, Phosphoramidon blocked the endothelin-converting enzyme activity that converts big ET-1 to ET-1 in a concentration-dependent manner, as assessed by the inhibition of the contractile response in rat aortic rings. At 1 µM, it caused 24 ± 5% inhibition; at 10 µM, 60 ± 9%; at 50 µM, 82 ± 2%; and at 500 µM, 88 ± 4% [5]. |
| ln Vivo |
In rats, phosphoramidon (0.25 mg/kg per min; iv) inhibits large endothelin-1's hypertensive effect[4]. Rats' porcine large endothelin-1-(1-39) pressor activity is blocked by phosphoramidon (1-30 mg/kg; IV; once)[5].
In ganglion-blocked anesthetized rats, intravenous administration of Phosphoramidon at 30 mg/kg just prior to big ET-1 (1 nmol/kg) significantly blocked the sustained pressor response typically produced by big ET-1 [5]. |
| Enzyme Assay |
Endothelin-converting enzyme (ECE) activity was assessed in a soluble enzyme fraction prepared from rabbit lung membranes. The detergent-solubilized fraction was incubated with 0.25 nmol of porcine big ET-1 in 125 µL of 50 mM Tris-HCl (pH 7.5) containing 10 µM thiorphan. The reaction mixture was incubated at 37°C for 30 minutes. To test inhibition, various concentrations of Phosphoramidon or 1,10-phenanthroline were included in the reaction. After incubation, the mixture was added to muscle baths containing rat aortic rings to measure contractile activity, which served as a bioassay for the generated ET-1. Results were normalized to the second contraction obtained with 50 mM KCl (% KClmax) [5].
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| Cell Assay |
Cells are plated in 6‑well plates at ~50% confluence. After 24 h, cells are treated with 10 μM 12 for 48 h. Cells are then washed with PBS, trypsinised, and resuspended in annexin‑V binding buffer. Staining is performed with annexin‑V‑FITC and propidium iodide, followed by incubation in the dark. Samples are analysed on a flow cytometer, and at least 10,000 cells are measured per sample. Results are reported as the percentage of annexin‑V/propidium‑iodide unstained cells in treated versus untreated (DMSO) samples. [1]
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| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats[4]
Doses: 0.25 mg/kg per min Route of Administration: intravenous (iv) injection Experimental Results: Markedly suppressed the hypertensive effect of big endothelin-1. In vivo experiments were performed on male Sprague-Dawley rats (200-250 g) anesthetized with Inactin (100 mg/kg i.p.). Catheters were inserted into a femoral artery and vein for measuring mean arterial pressure (MAP) and administering drugs. Autonomic neurotransmission was blocked by treatment with mecamylamine (3 mg/kg i.v.) and atropine (400 µg/kg i.v.). Rats were allowed to recover for 45 minutes. Subsequently, either big ET-1 or ET-1 (both at 1 nmol/kg) was administered i.v. with or without a protease inhibitor. For inhibition studies, various amounts of Phosphoramidon (1, 10, 30 mg/kg) were administered as an i.v. bolus 10-15 seconds prior to the administration of big ET-1 or ET-1 [5]. |
| References |
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| Additional Infomation |
Phosphoramidon is a microbial metabolite produced by Streptomyces tcrmshiensis and was found by a color screening method using Ehrlich reagent [1].
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| Molecular Formula |
C23H34N3NA2O10P
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| Molecular Weight |
588.48
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| Exact Mass |
587.162
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| CAS # |
164204-38-0
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| Related CAS # |
Phosphoramidon;36357-77-4
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| PubChem CID |
16219931
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| Appearance |
White to off-white solid powder
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| LogP |
1.01
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
39
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| Complexity |
834
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)OP(=O)(N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)[O-])[O-])O)O)O.[Na+].[Na+]
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| InChi Key |
OQKHVXFOYFBMDJ-ODIUWQMJSA-L
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| InChi Code |
InChI=1S/C23H34N3O10P.2Na/c1-11(2)8-16(26-37(33,34)36-23-20(29)19(28)18(27)12(3)35-23)21(30)25-17(22(31)32)9-13-10-24-15-7-5-4-6-14(13)15;;/h4-7,10-12,16-20,23-24,27-29H,8-9H2,1-3H3,(H,25,30)(H,31,32)(H2,26,33,34);;/q;2*+1/p-2/t12-,16-,17-,18-,19+,20+,23-;;/m0../s1
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| Chemical Name |
sodium (oxido(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)phosphoryl)-L-leucyl-L-tryptophanate
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| Synonyms |
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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. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (170.22 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6993 mL | 8.4965 mL | 16.9929 mL | |
| 5 mM | 0.3399 mL | 1.6993 mL | 3.3986 mL | |
| 10 mM | 0.1699 mL | 0.8496 mL | 1.6993 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04205565 | RECRUITING | Drug:Test group:L-oxiracetam Injection Drug:Control group:Oxiracetam Injection Drug:Placebo group:Placebo Injection |
Craniocerebral Injury | Nanjing Yoko Biomedical Co.,Ltd. | 2019-09-30 | Phase 3 |
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