Identification

Name
Ecabet
Accession Number
DB05265
Type
Small Molecule
Groups
Approved, Investigational
Description

Ecabet is a prescription eye drop for the treatment of dry eye syndrome. Ecabet represents a new class of molecules that increases the quantity and quality of mucin produced by conjunctival goblet cells and corneal epithelia. Mucin is a glycoprotein component of tear film that lubricates while retarding moisture loss from tear evaporation. Ecabet is currently marketed in Japan as an oral agent for treatment of gastric ulcers and gastritis.

Structure
Thumb
Synonyms
  • Ecabet
Product Ingredients
IngredientUNIICASInChI Key
Ecabet sodium51MO2B2OSB86408-72-2RCVIHORGZULVTN-YGJXXQMASA-M
International/Other Brands
Gastrom (Tanabe Mitsubishi, Japan)
Categories
UNII
2K02669KWP
CAS number
33159-27-2
Weight
Average: 380.498
Monoisotopic: 380.165744696
Chemical Formula
C20H28O5S
InChI Key
IWCWQNVIUXZOMJ-MISYRCLQSA-N
InChI
InChI=1S/C20H28O5S/c1-12(2)14-10-13-6-7-17-19(3,8-5-9-20(17,4)18(21)22)15(13)11-16(14)26(23,24)25/h10-12,17H,5-9H2,1-4H3,(H,21,22)(H,23,24,25)/t17-,19-,20-/m1/s1
IUPAC Name
(1R,4aS,10aR)-1,4a-dimethyl-7-(propan-2-yl)-6-sulfo-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylic acid
SMILES
[H][C@@]12CCC3=CC(C(C)C)=C(C=C3[C@@]1(C)CCC[C@@]2(C)C(O)=O)S(O)(=O)=O

Pharmacology

Indication

For the treatment of reflux oesophagitis and peptic ulcer disease.

Pharmacodynamics
Not Available
Mechanism of action

Ecabet reduces the survival of H. pylori in the stomach and inhibits pepsin activity in the gastric juice of experimental animals. Here we have investigated the effects of ecabet on some of the factors involved in the dynamics of the mucosal barrier, i.e. pepsins and mucins. Pepsin, acid and Helicobacter pylori are major factors in the pathophysiology of peptic ulcer disease and reflux oesophagitis. Ecabet also acts as an inhibitor of H. pylori NADPH oxidase as well as urease. Inhibition of these enzymes prevents bacterial adhesion to gastric mucosa.

TargetActionsOrganism
ANADPH oxidase organizer 1
antagonist
Human
AUrease subunit alpha
inhibitor
Enterobacter aerogenes
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Ecabet.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ecabet.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Ecabet.
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Ecabet.
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Ecabet.
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Ecabet.
AmitriptylinoxideThe serum concentration of Amitriptylinoxide can be increased when it is combined with Ecabet.
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Ecabet.
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Ecabet.
BoceprevirThe serum concentration of Ecabet can be decreased when it is combined with Boceprevir.
Food Interactions
Not Available

References

Synthesis Reference

Shinji Narisawa, "Aqueous ecabet sodium solution preparation." U.S. Patent US20040259905, issued December 23, 2004.

US20040259905
General References
Not Available
External Links
Human Metabolome Database
HMDB0015613
KEGG Drug
D07885
PubChem Compound
65781
PubChem Substance
99443230
ChemSpider
59201
ChEBI
135593
ChEMBL
CHEMBL2104585
PharmGKB
PA165958350
Drugs.com
Drugs.com Drug Page

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentDry Eye Syndrome (DES)1
2CompletedTreatmentDry Eye Syndromes1
2, 3CompletedTreatmentDry Eye Syndromes1
4Unknown StatusTreatmentDelayed Bleeding / Healing Ulcer / Quality of Ulcer1
Not AvailableCompletedTreatmentGastroesophageal Reflux Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00426 mg/mLALOGPS
logP1.5ALOGPS
logP4.93ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)-1.5ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.67 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity100.07 m3·mol-1ChemAxon
Polarizability41.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9357
Blood Brain Barrier+0.8758
Caco-2 permeable-0.63
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.8403
P-glycoprotein inhibitor IINon-inhibitor0.7504
Renal organic cation transporterNon-inhibitor0.8911
CYP450 2C9 substrateNon-substrate0.6979
CYP450 2D6 substrateNon-substrate0.8179
CYP450 3A4 substrateSubstrate0.5303
CYP450 1A2 substrateNon-inhibitor0.7918
CYP450 2C9 inhibitorNon-inhibitor0.8472
CYP450 2D6 inhibitorNon-inhibitor0.9023
CYP450 2C19 inhibitorNon-inhibitor0.718
CYP450 3A4 inhibitorNon-inhibitor0.8145
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9109
Ames testNon AMES toxic0.6719
CarcinogenicityCarcinogens 0.6053
BiodegradationNot ready biodegradable0.9876
Rat acute toxicity2.3482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9382
hERG inhibition (predictor II)Non-inhibitor0.588
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diterpenoids. These are terpene compounds formed by four isoprene units.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Diterpenoids
Direct Parent
Diterpenoids
Alternative Parents
Hydrophenanthrenes / Tetralins / 1-sulfo,2-unsubstituted aromatic compounds / Sulfonyls / Organosulfonic acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Abietane diterpenoid / Diterpenoid / Hydrophenanthrene / Phenanthrene / Tetralin / 1-sulfo,2-unsubstituted aromatic compound / Arylsulfonic acid or derivatives / Benzenoid / Sulfonyl / Organosulfonic acid
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Superoxide-generating nadph oxidase activator activity
Specific Function
Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in ...
Gene Name
NOXO1
Uniprot ID
Q8NFA2
Uniprot Name
NADPH oxidase organizer 1
Molecular Weight
41252.315 Da
References
  1. Kusumoto K, Kawahara T, Kuwano Y, Teshima-Kondo S, Morita K, Kishi K, Rokutan K: Ecabet sodium inhibits Helicobacter pylori lipopolysaccharide-induced activation of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells. Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G300-7. Epub 2004 Sep 30. [PubMed:15458921]
Kind
Protein
Organism
Enterobacter aerogenes
Pharmacological action
Yes
Actions
Inhibitor
General Function
Urease activity
Specific Function
Not Available
Gene Name
ureC
Uniprot ID
P18314
Uniprot Name
Urease subunit alpha
Molecular Weight
60304.12 Da
References
  1. Koizumi W, Tanabe S, Imaizumi H, Kida M, Ohida M, Koshida Y, Mitomi H, Hosaka Y, Nagaba S, Sasaki T, Higuchi K, Saigenji K: Inhibition of peptic ulcer relapse by ranitidine and ecabet independently of eradication of Helicobacter pylori: a prospective, controlled study versus ranitidine. Hepatogastroenterology. 2003 Mar-Apr;50(50):577-81. [PubMed:12749277]
  2. Takahashi S, Tanaka A: [Ecabet sodium]. Nihon Rinsho. 2002 Feb;60 Suppl 2:711-6. [PubMed:11979876]
  3. Adachi K, Ishihara S, Hashimoto T, Hirakawa K, Ishimura N, Niigaki M, Kaji T, Kawamura A, Sato H, Fujishiro H, Hattori S, Watanabe M, Kinoshita Y: Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen. Aliment Pharmacol Ther. 2001 Aug;15(8):1187-91. [PubMed:11472321]

Drug created on November 18, 2007 11:22 / Updated on August 02, 2018 07:36