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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:31:18 UTC
HMDB IDHMDB15056
Secondary Accession NumbersNone
Metabolite Identification
Common NameKetotifen
DescriptionKetotifen is only found in individuals that have used or taken this drug. It is a cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis. [PubChem]Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. Ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils have also been demonstrated. Ketotifen also inhibits cAMP phosphodiesterase. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include inhibition of the development of airway hyper-reactivity associated with activation of platelets by PAF (Platelet Activating Factor), inhibition of PAF-induced accumulation of eosinophils and platelets in the airways, suppression of the priming of eosinophils by human recombinant cytokines and antagonism of bronchoconstriction due to leukotrienes. Ketotifen inhibits of the release of allergic mediators such as histamine, leukotrienes C4 and D4(SRS-A) and PAF.
Structure
Thumb
Synonyms
ValueSource
AlawayKegg
Ketotifen fumarateHMDB
Ketotifene fumarateHMDB
Chemical FormulaC19H19NOS
Average Molecular Weight309.425
Monoisotopic Molecular Weight309.118734925
IUPAC Name2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),4,10,12-pentaen-8-one
Traditional Nameketotifen
CAS Registry Number34580-14-8
SMILES
CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12
InChI Identifier
InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3
InChI KeyInChIKey=ZCVMWBYGMWKGHF-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cycloheptathiophenes. These are polycyclic compounds containing a thiophene ring fused to a 7 member carbocyclic moiety. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassCycloheptathiophenes
Sub ClassNot Available
Direct ParentCycloheptathiophenes
Alternative Parents
Substituents
  • Cycloheptathiophene
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzenoid
  • Piperidine
  • Heteroaromatic compound
  • Thiophene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Anti-Allergic Agents
  • Antipruritics
  • Histamine H1 Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point191 °C (fumarate salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility7.87e-03 g/LNot Available
LogP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0079 mg/mLALOGPS
logP3.49ALOGPS
logP3.35ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)12.3ChemAxon
pKa (Strongest Basic)7.15ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.73 m3·mol-1ChemAxon
Polarizability34.61 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00920
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00920
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00920
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3695
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkKetotifen
NuGOwiki LinkHMDB15056
Metagene LinkHMDB15056
METLIN IDNot Available
PubChem Compound3827
PDB IDNot Available
ChEBI ID112957
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development.
Gene Name:
PDE8A
Uniprot ID:
O60658
Molecular weight:
86047.88
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
General function:
Involved in 3',5'-cyclic-AMP phosphodiesterase activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.
Gene Name:
PDE7A
Uniprot ID:
Q13946
Molecular weight:
55504.475
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular weight:
64351.765
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
  2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [16313925 ]
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain.
Gene Name:
PDE7B
Uniprot ID:
Q9NP56
Molecular weight:
51834.855
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland.
Gene Name:
PDE8B
Uniprot ID:
O95263
Molecular weight:
87973.225
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4C
Uniprot ID:
Q08493
Molecular weight:
79900.795
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
  2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [16313925 ]
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4D
Uniprot ID:
Q08499
Molecular weight:
91114.1
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
  2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [16313925 ]
General function:
Involved in 3',5'-cyclic-nucleotide phosphodiesterase activity
Specific function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular weight:
98142.155
References
  1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [1702263 ]
  2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [16313925 ]
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH (By similarity).
Gene Name:
PGD
Uniprot ID:
P52209
Molecular weight:
53139.56
References
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. [20235752 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
References
  1. Mita H, Shida T: Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes. Arzneimittelforschung. 1995 Jan;45(1):36-40. [7893266 ]
  2. Okabe S, Nakaji S, Tachibana M: Effect of ketotifen on acute gastric lesions and gastric secretion in rats. Jpn J Pharmacol. 1992 Jun;59(2):251-4. [1434122 ]
  3. Hashimoto T, Ohata H, Honda K: Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors. J Pharmacol Sci. 2006 Jan;100(1):82-7. Epub 2006 Jan 11. [16404130 ]
  4. Ito K, Sakamoto T, Hayashi Y, Morishita M, Shibata E, Sakai K, Takeuchi Y, Torii S: Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats. Eur J Pharmacol. 1996 Jul 4;307(3):291-8. [8836617 ]
  5. Yokoyama H, Iinuma K, Yanai K, Watanabe T, Sakurai E, Onodera K: Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. Methods Find Exp Clin Pharmacol. 1993 Apr;15(3):183-8. [8101246 ]
  6. Werner-Klein M, Goggel R, Westhof A, Erb KJ: Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulm Pharmacol Ther. 2008 Aug;21(4):648-56. Epub 2008 Apr 7. [18490184 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]