| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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Purity: ≥98%
Omapatrilat (also known as Vanlev; BMS-186716) is a novel investigational antihypertensive agent that acts as a potent dual inhibitor of the metalloproteases ACE (angiotensin converting enzyme) and NEP (neutral endopeptidase) with Ki values of 0.64 and 0.45 nM, respectively. Omapatrilat is heterocyclic dipeptide mimetic that has antihypertensive activity. NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling. The drug was promoted for possible uses in congestive heart failure.
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| ln Vitro |
Omapatrilat (Ki=0.45, 25, 0.64, 250 nM) shows poor action against ECE1, but significant potency for NEP, NEP2, and ACE, as well as moderately strong activity against APP [1]. Simpatril (10 mg/kg) produces rapid and potent suppression of renal NEP and ACE for 24 hours, respectively, according to in vitro autoradiography utilizing the particular radioligands for NEP and ACE inhibitors, 125I-RB104 and 125I-MK351A, respectively[4].
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| ln Vivo |
In numerous animal models with varying degrees of plasma renin activity, omapatrilat exhibits excellent blood pressure decrease. In a test using cynomolgus monkeys, it also dramatically increases urine sodium, ANP, and cGMP excretion. Between 10 and 24 hours, omapatrilat lowers mean arterial pressure (MAP) by around 40 mmHg below baseline. On day three, the systolic blood pressure is 38 mmHg lower when oral omapatrilat at 100 μM/kg is administered once daily as opposed to vehicle [2]. Omapatrilat is frequently utilized in experimental procedures pertaining to heart failure and hypertension. Omapatrilat, when taken orally over time, has been shown to improve endothelium independent vasorelaxation to ANP and decrease aortic leakiness and atheroma formation[3]. In rats, omapatrilat significantly reduces plasma ACE and increases plasma renin activity[4].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Omatrara has an absolute oral bioavailability of 20% to 30%, and its absorption is not affected by food intake. Metabolism/Metabolites Liver |
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| Additional Infomation |
Omapatrilat is a dipeptide. Omatrala is an investigational drug that simultaneously inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). Inhibition of NEP increases natriuretic peptide levels, increases urinary sodium excretion, dilates blood vessels, and reduces preload and ventricular remodeling. Due to concerns about angioedema, this drug has not been approved by the FDA. Omatrala is an angiopeptidase inhibitor with antihypertensive activity. Omatrala works by inhibiting angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). ACE inhibition inhibits the renin-angiotensin-aldosterone system, thereby reducing vasoconstriction. Inhibition of neutral endopeptidase (NEP) inhibits the hydrolysis of various endogenous vasoactive peptides, such as bradykinin and substance P. Since NEP is the main enzyme that degrades natriuretic peptides, NEP inhibition also leads to an increase in natriuretic peptide cycling. Ultimately, both effects result in vasodilation. Drug Indications Omatricilla is used to treat hypertension. Mechanism of Action Omatricilla binds to angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). This leads to a decrease in the production of the renin-angiotensin-aldosterone system and an increase in the natriuretic peptidase cycle. Pharmacodynamics Omatricilla is used to treat hypertension. It is an angiopeptidase inhibitor that simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Omatricilla lowers blood pressure by inhibiting the activity of angiotensin-converting enzyme (ACE), which causes vasoconstriction. However, unlike other drugs, omatricilla also inhibits another enzyme called neutral endopeptidase (NEP), which helps in vasodilation. In patients with salt-sensitive hypertension who typically do not respond well to ACE inhibitors, omatricilla is more effective than the ACE inhibitor lisinopril.
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| Molecular Formula |
C19H24N2O4S2
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|---|---|
| Molecular Weight |
408.53486
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| Exact Mass |
408.117
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| Elemental Analysis |
C, 55.86; H, 5.92; N, 6.86; O, 15.67; S, 15.70
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| CAS # |
167305-00-2
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| PubChem CID |
656629
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| Appearance |
White to gray solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
724.2±60.0 °C at 760 mmHg
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| Flash Point |
391.8±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.645
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| LogP |
1.65
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
568
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| Defined Atom Stereocenter Count |
4
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| SMILES |
O=C([C@@H]1CCC[C@](N21)([H])SCC[C@H](NC([C@@H](S)CC3=CC=CC=C3)=O)C2=O)O
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| InChi Key |
LVRLSYPNFFBYCZ-VGWMRTNUSA-N
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| InChi Code |
InChI=1S/C19H24N2O4S2/c22-17(15(26)11-12-5-2-1-3-6-12)20-13-9-10-27-16-8-4-7-14(19(24)25)21(16)18(13)23/h1-3,5-6,13-16,26H,4,7-11H2,(H,20,22)(H,24,25)/t13-,14-,15-,16-/m0/s1
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| Chemical Name |
(4S,7S,10aS)-4-((S)-2-mercapto-3-phenylpropanamido)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid
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| Synonyms |
BMS 186716; Vanlev; BMS186716; BMS-186716;
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ≥ 31 mg/mL (~75.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (10.40 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 42.5 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 (6.12 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4478 mL | 12.2390 mL | 24.4780 mL | |
| 5 mM | 0.4896 mL | 2.4478 mL | 4.8956 mL | |
| 10 mM | 0.2448 mL | 1.2239 mL | 2.4478 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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