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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.
Physicochemical Properties
| Molecular Formula | C18H24N2O5.2H2O | |
| Molecular Weight | 348.4 | |
| Exact Mass | 384.189 | |
| CAS # | 84680-54-6 | |
| Related CAS # | Enalaprilat-d5;349554-00-3;Enalaprilat-d5 sodium;1356922-29-6;Enalaprilat;76420-72-9 | |
| PubChem CID | 6917719 | |
| Appearance | White to off-white solid powder | |
| Boiling Point | 563.5ºC at 760 mmHg | |
| Melting Point | 211-215°C | |
| Flash Point | 294.6ºC | |
| Index of Refraction | 1.579 | |
| LogP | 1.326 | |
| Hydrogen Bond Donor Count | 5 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 8 | |
| Heavy Atom Count | 27 | |
| Complexity | 490 | |
| Defined Atom Stereocenter Count | 3 | |
| 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 | |
| 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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| 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 |
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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) |
Biological Activity
| 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]. | ||
| ln Vivo | In rabbits, enalaprilat dihydrate (0.01%–2.9% in the eyedrop solution) significantly lowers intraocular pressure (IOP)[3]. | ||
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| References |
[1]. Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol. 2007 Dec 22;577(1-3):1-6. [2]. Angiotensin-converting enzyme (ACE) inhibition attenuates insulin-like growth factor-I (IGF-I) induced cardiac fibroblast proliferation. Br J Pharmacol. 2000 Dec;131(8):1592-6. [3]. Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits. Acta Ophthalmol. 2010 May;88(3):337-41. |
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| Additional Infomation |
Enalaprilat dihydrate is the dihydrate form of enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor that is used (often in the form of its prodrug, enalapril) in the treatment of hypertension and heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is administered by intravenous injection. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor and an antihypertensive agent. It contains an enalaprilat (anhydrous). The active metabolite of ENALAPRIL and one of the potent, intravenously administered, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion. See also: Enalaprilat (annotation moved to). |
Solubility Data
| 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. 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. 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 corn oil and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |