| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
Angiotensin-converting enzyme (ACE).
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|---|---|
| ln Vitro |
TLR4 expression induced by LPS is inhibited by fosfenopril (0–10 μM, 5 minutes) [1]. LPS-activated NF-κB expression can be attenuated by fosfenopril (0–10 μM, 1 h) [1]. LPS-induced cytokine (IL-6, IL-1β, and TNF-α) expression is inhibited by fosfenopril [1].
Fosinoprilat is a potent inhibitor of ACE. It blocks the conversion of angiotensin I to the vasoconstrictor angiotensin II, leading to vasodilation and reduced blood pressure. The compound is the active metabolite of the prodrug fosinopril. |
| ln Vivo |
Dogs' glomerular filtration rate (GFR) and clearance of paraaminohippuric acid (PAH) are both increased by forfenopril (0.5 mg/kg bolus plus 0.1 mg/kg/min IV once) [3].
In vivo, fosinoprilat is the active metabolite responsible for the antihypertensive effects of fosinopril. It is formed by esterase-mediated hydrolysis of the prodrug. Fosinoprilat effectively lowers blood pressure and reduces cardiac workload in patients with hypertension and heart failure. |
| Enzyme Assay |
ACE inhibition is assessed using in vitro enzyme assays. Recombinant ACE or ACE from tissue extracts is incubated with a synthetic substrate (e.g., hippuryl-histidyl-leucine) in the presence of varying concentrations of fosinoprilat. The hydrolysis of the substrate is measured spectrophotometrically or by HPLC. IC50 values are calculated.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: THP1 Cell Tested Concentrations: 0, 0.25, 0.5, 1, 5, 10 μM Incubation Duration: 1 h Experimental Results: NF-κB protein expression was down-regulated. RT-PCR[1] Cell Types: THP1 Cell Tested Concentrations: 0, 0.25, 0.5, 1, 5 and 10 μM Incubation Duration: 5 minutes Experimental Results: Dose-dependent inhibition of TLR4 expression. Fosinoprilat cellular activity is evaluated in cell-based assays, such as measuring the inhibition of angiotensin II production in cultured endothelial cells or other ACE-expressing cells. Cells are treated with the compound, and the levels of angiotensin I and angiotensin II in the culture medium are measured by ELISA. |
| Animal Protocol |
Animal/Disease Models: Female Mongrel Dog (n=7)[3]
Doses: 0.5 mg/kg (1.1 mumol/kg) bolus plus 0.1 mg/kg/min (0.22 mumol/kg/min) Route of Administration: IV, one result Experimental Results: Increases para-aminohippuric acid (PAH) clearance and glomerular filtration rate (GFR) by 25% and 16% respectively without changing arterial pressure (AP). In vivo efficacy is studied in animal models of hypertension, such as spontaneously hypertensive rats. Fosinoprilat or its prodrug fosinopril is administered orally or intravenously. Blood pressure is measured by tail-cuff or telemetry. The compound's antihypertensive effect and its duration of action are assessed. |
| ADME/Pharmacokinetics |
Fosinoprilat has a molecular formula of C23H34NO5P and a molecular weight of 435.49 g/mol. It is a phosphinic acid derivative. The compound is the active metabolite of the prodrug fosinopril.
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| Toxicity/Toxicokinetics |
Safety data for fosinoprilat are well-established from the clinical use of fosinopril. Common adverse effects include cough, dizziness, and hyperkalemia. The compound is contraindicated in pregnancy.
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| References |
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| Additional Infomation |
Fosinoprilat is a phosphonate-containing N-acyl derivative of (4S)-cyclohexyl-L-proline. It is an angiotensin-converting enzyme (ACE) inhibitor, used in conjunction with the phosphonate prodrug fosinopril to treat hypertension and chronic heart failure. It has antihypertensive activity and is also an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor. Fosinoprilat belongs to the phosphonate class of compounds and is also a derivative of L-proline. Fosinoprilat is the active phosphonate metabolite of the prodrug [fosinopril], activated in vivo by esterases. It binds to zinc via its phosphonate group. Fosinoprilat is an angiotensin-converting enzyme inhibitor. The mechanism of action of Fosinoprilat is as an angiotensin-converting enzyme inhibitor. Fosinoprilat is a phosphonate-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive effects. Fosinopril specifically and competitively inhibits angiotensin-converting enzyme, thereby reducing the production of the potent vasoconstrictor angiotensin II, leading to decreased vasopressor activity. Furthermore, it reduces adrenal cortical aldosterone secretion mediated by angiotensin II, thereby reducing sodium retention and increasing water excretion.
See also: Fosinopril (active ingredient); Fosinopril sodium (active ingredient). Fosinoprilat (SQ 27,519) is the active metabolite of the ACE inhibitor fosinopril. It is not used as a drug itself but is the pharmacologically active form in vivo. Fosinopril is approved for the treatment of hypertension and chronic heart failure. |
| Molecular Formula |
C23H34NO5P
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|---|---|
| Molecular Weight |
435.5
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| Exact Mass |
435.217
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| Elemental Analysis |
C, 63.43; H, 7.87; N, 3.22; O, 18.37; P, 7.11
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| CAS # |
95399-71-6
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| Related CAS # |
Fosfenopril-d7;1279220-43-7
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| PubChem CID |
62956
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| Appearance |
White to off-white solid powder
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| Density |
1.238g/cm3
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| Boiling Point |
728.9ºC at 760mmHg
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| Melting Point |
>300ºC
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| Flash Point |
394.6ºC
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| Index of Refraction |
1.564
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| LogP |
4.099
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
30
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| Complexity |
627
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CCC(CC1)[C@@H]2C[C@H](N(C2)C(=O)CP(=O)(CCCCC3=CC=CC=C3)O)C(=O)O
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| InChi Key |
WOIWWYDXDVSWAZ-RTWAWAEBSA-N
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| InChi Code |
InChI=1S/C23H34NO5P/c25-22(17-30(28,29)14-8-7-11-18-9-3-1-4-10-18)24-16-20(15-21(24)23(26)27)19-12-5-2-6-13-19/h1,3-4,9-10,19-21H,2,5-8,11-17H2,(H,26,27)(H,28,29)/t20-,21+/m1/s1
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| Chemical Name |
(2S,4S)-4-cyclohexyl-1-[2-[hydroxy(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid
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| Synonyms |
SQ-27,519; SQ 27,519; SQ27519; 95399-71-6; SQ-27519; SQ 27519; fosfenopril; Fosinopril diacid; Fosinoprilic acid; Fosinoprilat
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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) |
DMSO : ~100 mg/mL (~229.63 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 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 (5.74 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 (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2962 mL | 11.4811 mL | 22.9621 mL | |
| 5 mM | 0.4592 mL | 2.2962 mL | 4.5924 mL | |
| 10 mM | 0.2296 mL | 1.1481 mL | 2.2962 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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