Omapatrilat
Identification
- Generic Name
- Omapatrilat
- DrugBank Accession Number
- DB00886
- Background
Omapatrilat is an investigational drug that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). The inhibition of NEP elevates natriuretic peptide levels, increasing excretion of sodium in urine, dilating blood vessels, and reducing preload and ventricular remodeling. This drug from BMS was not approved by the FDA due to angioedema safety concerns.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 408.53
Monoisotopic: 408.117749609 - Chemical Formula
- C19H24N2O4S2
- Synonyms
- Omapatrilat
- Omapatrilate
- External IDs
- BMS 186716
- BMS-186716
- BMS-186716-01
Pharmacology
- Indication
For the treatment of hypertension.
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- Pharmacodynamics
Omapatrilat is used to treat hypertension. Vasopeptidase inhibitor that simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Omapatrilat lowers blood pressure by inhibiting the action of the angiotensin converting enzyme (ACE), which causes blood vessels to constrict. But unlike other drugs, omapatrilat also inhibits another enzyme known as neutral endopeptidase (NEP), which helps blood vessels relax. Omapatrilat demonstrated greater reduction in blood pressure than the ACE inhibitor lisinopril in individuals with salt-sensitive hypertension who typically do not respond well to ACE inhibitors.
- Mechanism of action
Omapatrilat binds to both angiotensin converting enzyme and neutral endopeptidase. This results in a decrease renin-angiotensin-aldosterone production and increase natriuretic peptidase circulation.
Target Actions Organism ANeprilysin Not Available Humans UAngiotensin-converting enzyme Not Available Humans - Absorption
The absolute oral bioavailability of omapatrilat is 20% to 30% and the absorption is not affected by food intake.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Side effects include hyperkalemia, cough, hypotension, increased SrCr, and dizziness. Dizziness, diarrhea, vision disturbance, hypotension and angioedema
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Omapatrilat. Acebutolol Omapatrilat may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Omapatrilat. Acemetacin The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Omapatrilat. Acetylsalicylic acid The therapeutic efficacy of Omapatrilat can be decreased when used in combination with Acetylsalicylic acid. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Vanlev
Categories
- Drug Categories
- Agents Acting on the Renin-Angiotensin System
- Agents causing angioedema
- Agents causing hyperkalemia
- Agents that produce hypertension
- Angiotensin-Converting Enzyme Inhibitors
- Antihypertensive Agents
- Azepines
- Cardiovascular Agents
- Enzyme Inhibitors
- Metalloendopeptidases, antagonists & inhibitors
- Protease Inhibitors
- Sulfur Compounds
- Thiepins
- Vasopeptidase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / Piperidinecarboxylic acids / Benzene and substituted derivatives / Fatty amides / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Lactams / Alkylthiols / Azacyclic compounds / Thiohemiaminal derivatives show 8 more
- Substituents
- Alkylthiol / Alpha-amino acid or derivatives / Alpha-dipeptide / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid / Dialkylthioether show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 36NLI90E7T
- CAS number
- 167305-00-2
- InChI Key
- LVRLSYPNFFBYCZ-VGWMRTNUSA-N
- InChI
- 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
- IUPAC Name
- (4S,7S,10aS)-5-oxo-4-[(2S)-3-phenyl-2-sulfanylpropanamido]-octahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid
- SMILES
- [H][C@]12CCC[C@H](N1C(=O)[C@H](CCS2)NC(=O)[C@@H](S)CC1=CC=CC=C1)C(O)=O
References
- General References
- Rabkin SW, Klassen SS: Omapatrilat enhances adrenomedullin's reduction of cardiomyocyte cell death. Eur J Pharmacol. 2007 May 21;562(3):174-82. Epub 2007 Feb 8. [Article]
- External Links
- KEGG Drug
- D01970
- PubChem Compound
- 656629
- PubChem Substance
- 175426852
- ChemSpider
- 570983
- BindingDB
- 50073120
- ChEBI
- 135660
- ChEMBL
- CHEMBL289556
- ZINC
- ZINC000003809801
- PDBe Ligand
- FT8
- Wikipedia
- Omapatrilat
- PDB Entries
- 6h5w / 6h5x / 6suk / 6tt4
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 2.6 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0769 mg/mL ALOGPS logP 2.15 ALOGPS logP 2.06 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 3.77 Chemaxon pKa (Strongest Basic) -3.6 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 86.71 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 106.68 m3·mol-1 Chemaxon Polarizability 41.8 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9567 Blood Brain Barrier - 0.9219 Caco-2 permeable - 0.7793 P-glycoprotein substrate Substrate 0.7377 P-glycoprotein inhibitor I Non-inhibitor 0.7782 P-glycoprotein inhibitor II Non-inhibitor 0.9778 Renal organic cation transporter Non-inhibitor 0.8896 CYP450 2C9 substrate Non-substrate 0.7898 CYP450 2D6 substrate Non-substrate 0.9117 CYP450 3A4 substrate Non-substrate 0.5745 CYP450 1A2 substrate Non-inhibitor 0.8791 CYP450 2C9 inhibitor Non-inhibitor 0.8218 CYP450 2D6 inhibitor Non-inhibitor 0.8781 CYP450 2C19 inhibitor Non-inhibitor 0.7666 CYP450 3A4 inhibitor Inhibitor 0.5854 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.93 Ames test Non AMES toxic 0.8423 Carcinogenicity Non-carcinogens 0.9497 Biodegradation Not ready biodegradable 0.9922 Rat acute toxicity 2.0641 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9918 hERG inhibition (predictor II) Non-inhibitor 0.624
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0001900000-06a870edc3517eb3e004 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-05fr-1019200000-caf2986c36e426dcd044 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0356900000-ed215f40c83352f83086 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-2295100000-b1d22f0baa161bd20fe4 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0pbc-4796100000-592e7f1d9ba2294502aa Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-9611000000-84341795d5c987766309 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 196.0301764 predictedDarkChem Lite v0.1.0 [M-H]- 191.61449 predictedDeepCCS 1.0 (2019) [M+H]+ 195.5261764 predictedDarkChem Lite v0.1.0 [M+H]+ 194.01006 predictedDeepCCS 1.0 (2019) [M+Na]+ 195.5842764 predictedDarkChem Lite v0.1.0 [M+Na]+ 199.92259 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- General Function
- Zinc ion binding
- Specific Function
- Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptide...
- Gene Name
- MME
- Uniprot ID
- P08473
- Uniprot Name
- Neprilysin
- Molecular Weight
- 85513.225 Da
References
- Intengan HD, Schiffrin EL: Vasopeptidase inhibition has potent effects on blood pressure and resistance arteries in stroke-prone spontaneously hypertensive rats. Hypertension. 2000 Jun;35(6):1221-5. [Article]
- Azizi M, Massien C, Michaud A, Corvol P: In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor. Hypertension. 2000 Jun;35(6):1226-31. [Article]
- McClean DR, Ikram H, Garlick AH, Richards AM, Nicholls MG, Crozier IG: The clinical, cardiac, renal, arterial and neurohormonal effects of omapatrilat, a vasopeptidase inhibitor, in patients with chronic heart failure. J Am Coll Cardiol. 2000 Aug;36(2):479-86. [Article]
- Troughton RW, Rademaker MT, Powell JD, Yandle TG, Espiner EA, Frampton CM, Nicholls MG, Richards AM: Beneficial renal and hemodynamic effects of omapatrilat in mild and severe heart failure. Hypertension. 2000 Oct;36(4):523-30. [Article]
- Burrell LM, Droogh J, Man in't Veld O, Rockell MD, Farina NK, Johnston CI: Antihypertensive and antihypertrophic effects of omapatrilat in SHR. Am J Hypertens. 2000 Oct;13(10):1110-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
- Gene Name
- ACE
- Uniprot ID
- P12821
- Uniprot Name
- Angiotensin-converting enzyme
- Molecular Weight
- 149713.675 Da
References
- Azizi M, Massien C, Michaud A, Corvol P: In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor. Hypertension. 2000 Jun;35(6):1226-31. [Article]
- Ferdinand KC: Advances in antihypertensive combination therapy: benefits of low-dose thiazide diuretics in conjunction with omapatrilat, a vasopeptidase inhibitor. J Clin Hypertens (Greenwich). 2001 Sep-Oct;3(5):307-12. [Article]
- Heudi O, Ramirez-Molina C, Marshall P, Amour A, Peace S, McKeown S, Abou-Shakra F: Investigation of bradykinin metabolism in human and rat plasma in the presence of the dual ACE/NEP inhibitors GW660511X and omapatrilat. J Pept Sci. 2002 Nov;8(11):591-600. [Article]
- Neal B, MacMahon S, Ohkubo T, Brnabic A, Tonkin A: Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease. J Renin Angiotensin Aldosterone Syst. 2002 Dec;3(4):270-6. [Article]
- Trippodo NC, Fox M, Monticello TM, Panchal BC, Asaad MM: Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril. J Cardiovasc Pharmacol. 1999 Dec;34(6):782-90. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:45