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Record Information
Version2.0
Creation Date2009-07-30 17:59:03 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3524
Identification
Common NameOmeprazole
ClassSmall Molecule
DescriptionOmeprazole is a highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers, dyspepsia, peptic ulcer disease , gastroesophageal reflux disease and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of Gastric Parietal Cells.--Pubchem. Omeprazole is one of the most widely prescribed drugs internationally and is available over the counter in some countries.
Compound Type
  • Anti-Ulcer Agent
  • Drug
  • Enzyme Inhibitor
  • Ether
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Proton Pump Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
( -)-Omeprazole
(-)-Omeprazole
(S)-(-)-Omeprazole
(S)-Omeprazole
2,3,5-Trimethylpyridine/Omeprazole
Antra
Antra MUPS
Audazol
Aulcer
Belmazol
Ceprandal
Danlox
Demeprazol
Desec
Dizprazol
Dudencer
Elgam
Emeproton
Epirazole
Erbolin
Esomeprazole
Esomperazole
Exter
Gasec
Gastrimut
Gastroloc
Gibancer
Indurgan
Inhibitron
Inhipump
Lensor
Logastric
Lomac
Losec
Mepral
Miol
Miracid
Mopral
Morecon
Nexiam
Nexium
Nexium IV
Nilsec
Nopramin
Nuclosina
Ocid
Olexin
Omapren
Omebeta 20
Omed
Omegast
OMEP
Omepradex
Omepral
Omeprazol
Omeprazole Pellets
Omeprazolum
Omeprazon
Omeprol
Omesek
Omez
Omezol
Omezolan
Omid
Omisec
Omizac
OMP
Ompanyt
OMZ
Ortanol
Osiren
Ozoken
Paprazol
Parizac
Pepticum
Pepticus
Peptilcer
Prazentol
Prazidec
Prazolit
Prestwick_808
Prilosec
Prilosec OTC
Procelac
Proclor
Prysma
Ramezol
Regulacid
Result
Sanamidol
Secrepina
Tedec Ulceral
Ulceral
Ulcesep
Ulcometion
Ulcozol
Ulcsep
Ulsen
Ultop
Ulzol
Victrix
Zefxon
Zegerid
Zepral
Zimor
Zoltum
Chemical FormulaC17H19N3O3S
Average Molecular Mass345.416 g/mol
Monoisotopic Mass345.115 g/mol
CAS Registry Number73590-58-6
IUPAC Name6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole
Traditional Nameomeprazole
SMILESCOC1=CC2=C(C=C1)N=C(N2)S(=O)CC1=C(C)C(OC)=C(C)C=N1
InChI IdentifierInChI=1/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)
InChI KeyInChIKey=SUBDBMMJDZJVOS-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as sulfinylbenzimidazoles. These are polycyclic aromatic compounds containing a sulfinyl group attached at the position 2 of a benzimidazole moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzimidazoles
Sub ClassSulfinylbenzimidazoles
Direct ParentSulfinylbenzimidazoles
Alternative Parents
Substituents
  • Sulfinylbenzimidazole
  • Anisole
  • Alkyl aryl ether
  • Methylpyridine
  • Pyridine
  • Benzenoid
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Sulfoxide
  • Azacycle
  • Ether
  • Sulfinyl compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point155°C
Boiling PointNot Available
SolubilityVery slightly soluble
LogP2.23
Predicted Properties
PropertyValueSource
Water Solubility0.36 g/LALOGPS
logP1.66ALOGPS
logP2.43ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)9.29ChemAxon
pKa (Strongest Basic)4.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.1 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.66 m³·mol⁻¹ChemAxon
Polarizability37.45 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udj-0902000000-cfa5184c794ea62ab995JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-1669000000-51f9342d7e4bbd0356b2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-002f-0900000000-412912cbbcdbd1b34699JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0901000000-189e81fb724041d50498JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0f6t-0900000000-db101d248a4e861d4c3bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0uds-0900000000-f579fb74ac97c56dd3ebJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-eefbf9686f0313da581eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-363d6954875894f433baJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f6t-1900000000-d8c64d496f1d9b3ed465JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-1669000000-51f9342d7e4bbd0356b2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f6t-0900000000-d21755acc44ff2d29cfaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f80-2900000000-9989d19c171c612ea3dcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0900000000-f74adb7f41e2d390b602JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0509000000-a35086072388d122723eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0902000000-cf6c80499c6b8e76c5d5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ul9-3900000000-2356754b2ae17bd3bc19JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-0709000000-1b29375937cfcb406414JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-002b-0900000000-3383df9e4bfd7979d5e5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-0900000000-4fb7ec8321857498646dJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureThe delayed-release capsule are enteric-coated (as omeprazole is acid-labile) so the absorption of omprazole begins once the granules leave the stomach. Absorption is rapid. Peak plasma levels occur within 0.5 - 3.5 hours. The absolute bioavailability (compared with intravenous administration) of the delayed-release capsule is 30-40% at doses of 20 - 40 mg, due to presystemic metabolism. This value increases slightly when given repeatedly. Based on a relative bioavailability study, the AUC and Cmax of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively. Interestingly, when the 40 mg delayed release capsule is given with or without applesauce, it is bioequivalent. However, when the 20 mg delayed release capsule is given with the same conditions, it is not bioequivalent. When the same capsule is given to the elderly, bioavailability increases. Omeprazole was 76% bioavailable.
Mechanism of ToxicityOmeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity.
MetabolismHepatic. Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system. The two primary CYP isozymes involved are CYP2C19 and CYP3A4. Metabolism is stereoselective in which the S-isomer is converted to 5'O-desmethylomeprazole via CYP2C19. CYP3A4 converts the S-isomer to 3-hydroxyomeprazole. The R-isomer is converted to 5-hydroxyomeprazole by CYP2C19. CYP3A4 converts the R-isomer to any four different metabolites: 5-hydroxyomeprazole (5-OH OME), omeprazole sulfone (OME sulfone), 5'-O-desmethylomeprazole (5'-desmethyl OME), and 3-hydroxyomeprazole (3-OH OME). Route of Elimination: Urinary excretion is a primary route of excretion of omeprazole metabolites. Little, if any unchanged drug was excreted in the urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recovered in the feces. Half Life: 0.5-1 hour (healthy subjects, delayed-release capsule); 3 hours (hepatic impairment)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesOmeprazole is indicated for the treatment of duodenal ulcers, benign gastric ulcers, gastroesophageal reflux disease (GERD), heartburn and other symptoms associated with GERD, erosive esophagitis, and long-term treatment of pathological hypersecretory conditions like Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis.
Minimum Risk LevelNot Available
Health Effectsmay include bone rebuild interference and B12 vitamin reduction. [Wikipedia]
SymptomsSymptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00338
HMDB IDHMDB01913
PubChem Compound ID4594
ChEMBL IDCHEMBL1503
ChemSpider ID4433
KEGG IDC07324
UniProt IDNot Available
OMIM ID
ChEBI ID7772
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOmeprazole
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOmeprazole
References
Synthesis Reference

Arne E. Brandstrom, Bo R. Lamm, “Processes for the preparation of omeprazole and intermediates therefore.” U.S. Patent US4620008, issued October, 1982.

MSDSLink
General References
  1. Yang YX, Lewis JD, Epstein S, Metz DC: Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53. [17190895 ]
  2. FDA label
  3. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Hydrogen:potassium-exchanging atpase activity
Specific Function:
Required for stabilization and maturation of the catalytic proton pump alpha subunit and may also involved in cell adhesion and establishing epithelial cell polarity.
Gene Name:
ATP4B
Uniprot ID:
P51164
Molecular Weight:
33366.95 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.25 uMNot AvailableBindingDB 50241343
IC500.28 uMNot AvailableBindingDB 50241343
IC500.37 uMNot AvailableBindingDB 50241343
IC502 uMNot AvailableBindingDB 50241343
IC503.8 uMNot AvailableBindingDB 50241343
References
  1. Sanfilippo PJ, Urbanski M, Press JB, Hajos ZG, Shriver DA, Scott CK: Synthesis of (aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity. J Med Chem. 1988 Sep;31(9):1778-85. [2842503 ]
  2. Terauchi H, Tanitame A, Tada K, Nakamura K, Seto Y, Nishikawa Y: Nicotinamide derivatives as a new class of gastric H+/K(+)-ATPase inhibitors. 1. Synthesis and structure-activity relationships of N-substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides. J Med Chem. 1997 Jan 31;40(3):313-21. [9022797 ]
  3. Adelstein GW, Yen CH, Haack RA, Yu S, Gullikson G, Price DV, Anglin C, Decktor DL, Tsai H, Keith RH: Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase. J Med Chem. 1988 Jun;31(6):1215-20. [2836591 ]
  4. Yoon SH, Seo S, Lee Y, Hwang S, Kim DY: Syntheses of 2-[(3,5-dimethyl-4-methoxypyridyl)alkyl]-benzothiazolidine derivatives as a potential gastric H+/K(+)-ATPase inhibitor. Bioorg Med Chem Lett. 1998 Jul 21;8(14):1909-12. [9873457 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5017.7 uMNot AvailableBindingDB 50241343
IC5089 uMNot AvailableBindingDB 50241343
IC5091.2 uMNot AvailableBindingDB 50241343
IC5097.2 uMNot AvailableBindingDB 50241343
References
  1. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF: Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):551-7. [11770010 ]
  2. Pajeva IK, Wiese M: Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J Med Chem. 2002 Dec 19;45(26):5671-86. [12477351 ]
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
References
  1. Dzeletovic N, McGuire J, Daujat M, Tholander J, Ema M, Fujii-Kuriyama Y, Bergman J, Maurel P, Poellinger L: Regulation of dioxin receptor function by omeprazole. J Biol Chem. 1997 May 9;272(19):12705-13. [9139728 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory45 uMNot AvailableBindingDB 50241343
References
  1. Afzelius L, Zamora I, Masimirembwa CM, Karlen A, Andersson TB, Mecucci S, Baroni M, Cruciani G: Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J Med Chem. 2004 Feb 12;47(4):907-14. [14761192 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5078 uMNot AvailableBindingDB 50241343
References
  1. Roy K, Pratim Roy P: Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques. Eur J Med Chem. 2009 Jul;44(7):2913-22. doi: 10.1016/j.ejmech.2008.12.004. Epub 2008 Dec 16. [19128860 ]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach.
Gene Name:
ATP4A
Uniprot ID:
P20648
Molecular Weight:
114117.74 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]