Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:31 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2873
Identification
Common NameEsomeprazole
ClassSmall Molecule
DescriptionEsomeprazole is only found in individuals that have used or taken this drug. It is a highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of gastric parietal cells. [PubChem]Esomeprazole 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, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.
Compound Type
  • Anti-Ulcer Agent
  • Drug
  • Enzyme Inhibitor
  • Ether
  • Histamine Antagonist
  • Metabolite
  • Organic Compound
  • Proton Pump Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Omeprazole
(-)-Omeprazole
(R)-(+)-Omeprazole
(S)-Omeprazole
Alenia
Awa-Block
Axagon
Cor
Cronopep
Emanera
Emep
Emozul
ES-OD
Esmep
Eso
Esofag
Esogastrosedol
Esolok
Esomarfan
Esomenta
Esomep
Esomeprazol
Esomeprazol Genfar
Ésoméprazole
Esomeprazolum
Esopral
Esorest
Lucen
Nexiam
Nexium
Nexium i.v.
Perprazole
Chemical FormulaC17H19N3O3S
Average Molecular Mass345.416 g/mol
Monoisotopic Mass345.115 g/mol
CAS Registry Number161796-78-7
IUPAC Name5-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole
Traditional Name5-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole
SMILESCOC1=CC2=C(NC(=N2)[S@@](=O)CC2=NC=C(C)C(OC)=C2C)C=C1
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)/t24-/s2
InChI KeyInChIKey=SUBDBMMJDZJVOS-FQKVKQEKNA-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
  • 5-methoxy-2-\{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl\}-1H-benzimidazole (CHEBI:50275 )
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point155°C
Boiling PointNot Available
Solubility3.53e-01 g/L
LogP0.6
Predicted Properties
PropertyValueSource
Water Solubility0.35 g/LALOGPS
logP1.66ALOGPS
logP2.43ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)9.68ChemAxon
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
Polarizability35.81 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udj-0902000000-d7c360235f936b712320View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0509000000-a35086072388d122723eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0902000000-cf6c80499c6b8e76c5d5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ul9-3900000000-2356754b2ae17bd3bc19View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-0709000000-1b29375937cfcb406414View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-002b-0900000000-3383df9e4bfd7979d5e5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-0900000000-4fb7ec8321857498646dView in MoNA
Toxicity Profile
Route of ExposureOral
Mechanism of ToxicityEsomeprazole 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, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.
MetabolismMainly hepatic. Esomeprazole is completely metabolized by the cytochrome P450 system via CYP2C19 and CYP3A4. Metabolism produces inactive hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. Less than 1% of the parent drug is excreted in urine. Route of Elimination: Approximately 80% of the administered dose of esomeprazole is excreted as metabolites in urine and the remaining 20% is excreted in feces. Half Life: 1-1.5 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use. Used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD) and Zollinger-Ellison syndrome. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsBlurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating.
SymptomsBlurred vision, confusion, drowsiness, dry mouthflushingheadache, nausea, rapid heartbeat, sweating.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00736
HMDB IDHMDB14874
PubChem Compound ID9579578
ChEMBL IDCHEMBL1201320
ChemSpider ID7853936
KEGG IDC07324
UniProt IDNot Available
OMIM ID
ChEBI ID50275
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEsomeprazole
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEsomeprazole
References
Synthesis Reference

Manne Reddy, “Amorphous hydrates of esomeprazole magnesium and process for the preparation thereof.” U.S. Patent US20040167173, issued August 26, 2004.

MSDST3D2873.pdf
General References
  1. Lind T, Rydberg L, Kyleback A, Jonsson A, Andersson T, Hasselgren G, Holmberg J, Rohss K: Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000 Jul;14(7):861-7. [10886041 ]
  2. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular Weight:
112895.01 Da
References
  1. Bendsoe N, Ronquist G: Inhibition of the L-dopa transport system in human epidermal Langerhans cells by omeprazole and its analogues. Amino Acids. 2004 Feb;26(1):19-26. Epub 2003 Dec 18. [14752612 ]
  2. Shin JM, Sachs G: Differences in binding properties of two proton pump inhibitors on the gastric H+,K+-ATPase in vivo. Biochem Pharmacol. 2004 Dec 1;68(11):2117-27. [15498502 ]
  3. Dufner MM, Kirchhoff P, Remy C, Hafner P, Muller MK, Cheng SX, Tang LQ, Hebert SC, Geibel JP, Wagner CA: The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands. Am J Physiol Gastrointest Liver Physiol. 2005 Dec;289(6):G1084-90. Epub 2005 Aug 18. [16109841 ]
  4. Kukanich B, Lascelles BD, Aman AM, Mealey KL, Papich MG: The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs. J Vet Pharmacol Ther. 2005 Oct;28(5):461-6. [16207309 ]
  5. Sharara AI: Rabeprazole: the role of proton pump inhibitors in Helicobacter pylori eradication. Expert Rev Anti Infect Ther. 2005 Dec;3(6):863-70. [16307499 ]
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 potassium absorption in various tissues.
Gene Name:
ATP12A
Uniprot ID:
P54707
Molecular Weight:
115509.45 Da
References
  1. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. [15258107 ]
  2. Miner P: Review article: relief of symptoms in gastric acid-related diseases--correlation with acid suppression in rabeprazole treatment. Aliment Pharmacol Ther. 2004 Nov;20 Suppl 6:20-9. [15496215 ]
  3. Capendeguy O, Horisberger JD: The role of the third extracellular loop of the Na+,K+-ATPase alpha subunit in a luminal gating mechanism. J Physiol. 2005 May 15;565(Pt 1):207-18. Epub 2005 Mar 17. [15774534 ]
  4. Kiley CA, Cragin DJ, Roth BJ: Omeprazole-associated digoxin toxicity. South Med J. 2007 Apr;100(4):400-2. [17458401 ]
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:
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
IC5077.98 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 ]