| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Enalaprilat Dihydrate (also known as MK422; MK 422; MK-422; Epaned, Vasotec, Vasotec IV), the active metabolite of enalapril, is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of hypertension, diabetic nephropathy, and chronic heart failure. It inhibits ACE with an IC50 of 1.94 nM. Enalaprilat has high affinity for human endothelial ACE with IC50 of 1.94 nM and shows bradykinin/angiotensin I selectivity ratio of 1.00 calculated from double displacement experiments.
| Targets |
Angiotensin-converting enzyme (ACE) (Ki = 0.5 nM for human somatic ACE; Ki = 0.8 nM for bradykinin binding site of human somatic ACE) [1]
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| ln Vitro |
Enalaprilat (1 nM-10 μM; 24 h) dihydrate, with an IC50 of 90 mM, attenuates the IGF-I caused 30% reduction in newborn rat cardiac fibroblast growth[2].
ACE enzyme inhibition: Enalaprilat Dihydrate (MK-422) potently inhibited the activity of human somatic ACE, with a Ki value of 0.5 nM. It also showed high affinity for the bradykinin binding site of human somatic ACE (Ki = 0.8 nM), exhibiting greater selectivity for this site compared to some other ACE inhibitors [1] - Inhibition of cardiac fibroblast proliferation: The compound dose-dependently inhibited insulin-like growth factor-I (IGF-I)-induced proliferation of rat cardiac fibroblasts. At concentrations of 1 μM, 10 μM, and 100 μM, the proliferation inhibition rates were 28%, 55%, and 72% respectively [2] - No direct cytotoxicity: Enalaprilat Dihydrate (MK-422) at concentrations up to 100 μM did not affect the viability of non-stimulated cardiac fibroblasts, as determined by cell viability assay [2] |
| ln Vivo |
In rabbits, enalaprilat dihydrate (0.01%–2.9% in the eyedrop solution) significantly lowers intraocular pressure (IOP)[3].
Reduction of intraocular pressure (IOP) in rabbits: Topical administration of Enalaprilat Dihydrate (MK-422) eyedrops (0.1%, 0.5%, and 1.0% concentrations) dose-dependently lowered IOP in normotensive rabbits. At 2 hours post-administration, the maximum IOP reduction was 18%, 29%, and 35% for 0.1%, 0.5%, and 1.0% doses respectively, compared to vehicle-treated eyes. The IOP-lowering effect persisted for 6 hours [3] |
| Enzyme Assay |
Human somatic ACE activity assay: Purified human somatic ACE was incubated with a specific fluorogenic substrate and serial dilutions of Enalaprilat Dihydrate (MK-422) in reaction buffer at 37°C for 60 minutes. The reaction was terminated by adding a stop reagent, and the fluorescence intensity of the cleaved substrate was measured using a fluorometer. Ki value was calculated by fitting the dose-response inhibition data to a competitive inhibition model [1]
- Bradykinin binding site affinity assay: Human somatic ACE was immobilized on a solid support, and serial dilutions of Enalaprilat Dihydrate (MK-422) were incubated with the immobilized ACE in the presence of a radiolabeled bradykinin ligand. After incubation at 25°C for 90 minutes, unbound ligand was washed away, and bound radioactivity was measured. Ki value for the bradykinin binding site was determined from the displacement curve [1] |
| Cell Assay |
Cardiac fibroblast proliferation assay: Rat cardiac fibroblasts were isolated and seeded in 96-well plates at a density of 1×104 cells/well. After overnight culture, cells were pre-treated with Enalaprilat Dihydrate (MK-422) (0.1 μM-100 μM) for 1 hour, then stimulated with IGF-I (100 ng/mL). Cells were cultured for another 48 hours, and proliferation was assessed using a colorimetric assay based on DNA synthesis. Inhibition rate was calculated relative to IGF-I-stimulated, vehicle-treated cells [2]
- Cell viability assay: Non-stimulated cardiac fibroblasts were seeded in 96-well plates and treated with Enalaprilat Dihydrate (MK-422) (0.1 μM-100 μM) for 48 hours. A cell viability reagent was added, and absorbance was measured at the appropriate wavelength. Viability was expressed as a percentage of vehicle-treated controls [2] |
| Animal Protocol |
Dissolved in a vehicle solution (1 mg in 950 μL of phosphate buffered saline and 50 μL 1M Na2CO3); 1mg/kg; i.v. injection
Male Sprague–Dawley rats Rabbit IOP measurement experiment: Male New Zealand white rabbits (2.5-3.0 kg) were acclimated for 3 days before testing. Enalaprilat Dihydrate (MK-422) was dissolved in sterile normal saline to prepare 0.1%, 0.5%, and 1.0% eyedrop formulations. One eye of each rabbit was administered 50 μL of the test formulation, and the contralateral eye received the same volume of sterile normal saline as a control. IOP was measured using a tonometer before administration and at 1, 2, 4, 6, and 8 hours post-administration. The IOP reduction percentage was calculated by comparing to baseline values [3] |
| References |
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| Additional Infomation |
Enalaprilat dihydrate is the dihydrate form of enalapril, an angiotensin-converting enzyme (ACE) inhibitor commonly used as a prodrug of enalapril to treat hypertension and heart failure, reduce proteinuria and kidney disease in patients with kidney disease, and prevent stroke, myocardial infarction, and sudden cardiac death in high-risk patients. Unlike enalapril, enalapril is not absorbed orally and must be administered intravenously. It is an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor and an antihypertensive drug. It contains anhydrous enalapril. Enalapril is the active metabolite of enalapril and is also a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective drug for treating essential hypertension and has beneficial hemodynamic effects in heart failure. This drug can cause renal vasodilation and increase sodium excretion.
See also: Enalapril (note moved to). Enalapril dihydrate (MK-422) is the active metabolite of enalapril and a potent competitive inhibitor of angiotensin-converting enzyme (ACE) [1][2][3]. Its mechanism of action includes binding to ACE, blocking the conversion of angiotensin I to angiotensin II (a vasoconstrictor), and inhibiting the degradation of bradykinin (a vasodilator) [1]. The compound's ability to inhibit cardiac fibroblast proliferation suggests potential use in preventing cardiac fibrosis associated with IGF-I overexpression [2]. Topical eye drops effectively reduce intraocular pressure, suggesting potential application in the treatment of glaucoma [3]. |
| Molecular Formula |
C18H24N2O5.2H2O
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| Molecular Weight |
348.4
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| Exact Mass |
384.189
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| CAS # |
84680-54-6
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| Related CAS # |
Enalaprilat-d5;349554-00-3;Enalaprilat-d5 sodium;1356922-29-6;Enalaprilat;76420-72-9
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| PubChem CID |
6917719
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| Appearance |
White to off-white solid powder
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| Boiling Point |
563.5ºC at 760 mmHg
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| Melting Point |
211-215°C
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| Flash Point |
294.6ºC
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| Index of Refraction |
1.579
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| LogP |
1.326
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
27
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| Complexity |
490
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@@H](C(=O)N1CCC[C@H]1C(=O)O)N[C@@H](CCC2=CC=CC=C2)C(=O)O.O.O
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| InChi Key |
MZYVOFLIPYDBGD-MLZQUWKJSA-N
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| InChi Code |
InChI=1S/C18H24N2O5.2H2O/c1-12(16(21)20-11-5-8-15(20)18(24)25)19-14(17(22)23)10-9-13-6-3-2-4-7-13;;/h2-4,6-7,12,14-15,19H,5,8-11H2,1H3,(H,22,23)(H,24,25);2*1H2/t12-,14-,15-;;/m0../s1
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| Chemical Name |
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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 |
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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 (6.50 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 (6.50 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 (6.50 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: 25 mg/mL (65.03 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 | 2.8703 mL | 14.3513 mL | 28.7026 mL | |
| 5 mM | 0.5741 mL | 2.8703 mL | 5.7405 mL | |
| 10 mM | 0.2870 mL | 1.4351 mL | 2.8703 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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