T3DB: Esomeprazole

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (7)XML

Targets (7)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:31 UTC

Update Date

2014-12-24 20:25:52 UTC

Accession Number

T3D2873

Identification

Common Name

Esomeprazole

Class

Small Molecule

Description

Esomeprazole 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

MOL SDF PDB SMILES InChI

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 Formula

C₁₇H₁₉N₃O₃S

Average Molecular Mass

345.416 g/mol

Monoisotopic Mass

345.115 g/mol

CAS Registry Number

161796-78-7

IUPAC Name

5-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole

Traditional Name

5-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole

SMILES

COC1=CC2=C(NC(=N2)[S@@](=O)CC2=NC=C(C)C(OC)=C2C)C=C1

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzimidazoles

Sub Class

Sulfinylbenzimidazoles

Direct Parent

Sulfinylbenzimidazoles

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

5-methoxy-2-\{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl\}-1H-benzimidazole (CHEBI:50275 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	155°C
Boiling Point	Not Available
Solubility	3.53e-01 g/L
LogP	0.6

Predicted Properties

Property	Value	Source
Water Solubility	0.35 g/L	ALOGPS
logP	1.66	ALOGPS
logP	2.43	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	9.68	ChemAxon
pKa (Strongest Basic)	4.77	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	77.1 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	93.66 m³·mol⁻¹	ChemAxon
Polarizability	35.81 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0udj-0902000000-d7c360235f936b712320	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0f7t-0900000000-f43785dbdafca5df5996	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0006-0900000000-e0837329e37e32c98da2	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0509000000-a35086072388d122723e	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0902000000-cf6c80499c6b8e76c5d5	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0ul9-3900000000-2356754b2ae17bd3bc19	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0007-0709000000-1b29375937cfcb406414	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-002b-0900000000-3383df9e4bfd7979d5e5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-0900000000-4fb7ec8321857498646d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0007-0809000000-40107975e9855389175a	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0900000000-ce24ac86003c1fd0c915	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-0900000000-7094bcd15e524be40740	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0907000000-7d804584599dc64c2e69	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0f6t-0900000000-cd37c0cf17dabe7285d1	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00m0-0900000000-c05d93e4947b35f8cede	2021-09-24	View Spectrum

Toxicity Profile

Route of Exposure

Oral

Mechanism of Toxicity

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.

Metabolism

Mainly 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Used 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 Level

Not Available

Health Effects

Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating.

Symptoms

Blurred vision, confusion, drowsiness, dry mouthflushingheadache, nausea, rapid heartbeat, sweating.

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

50275

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Esomeprazole

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Esomeprazole

References

Synthesis Reference

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

MSDS

T3D2873.pdf

General References

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 ]
Drugs.com [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Sodium/potassium-transporting ATPase subunit alpha-1

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

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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

2. Potassium-transporting ATPase alpha chain 2

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

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 ]
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 ]
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 ]
Kiley CA, Cragin DJ, Roth BJ: Omeprazole-associated digoxin toxicity. South Med J. 2007 Apr;100(4):400-2. [17458401 ]

Target Details

3. Potassium-transporting ATPase subunit beta

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

Type	Value	Assay Type	Assay Source
IC50	0.25 uM	Not Available	BindingDB 50241343
IC50	0.28 uM	Not Available	BindingDB 50241343
IC50	0.37 uM	Not Available	BindingDB 50241343
IC50	2 uM	Not Available	BindingDB 50241343
IC50	3.8 uM	Not Available	BindingDB 50241343

References

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 ]
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 ]
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 ]
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 ]

Target Details

4. Multidrug resistance protein 1

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

Type	Value	Assay Type	Assay Source
IC50	17.7 uM	Not Available	BindingDB 50241343
IC50	89 uM	Not Available	BindingDB 50241343
IC50	91.2 uM	Not Available	BindingDB 50241343
IC50	97.2 uM	Not Available	BindingDB 50241343

References

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 ]
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 ]

Target Details

5. Cytochrome P450 2C9

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

Type	Value	Assay Type	Assay Source
Inhibitory	45 uM	Not Available	BindingDB 50241343

References

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 ]

Target Details

6. Cytochrome P450 3A4

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

Type	Value	Assay Type	Assay Source
IC50	77.98 uM	Not Available	BindingDB 50241343

References

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 ]

Target Details

7. Potassium-transporting ATPase alpha chain 1

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

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Esomeprazole (T3D2873)

Structure for T3D2873: Esomeprazole

Targets

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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