Details of the Drug

General Information of Drug (ID: DM74XKS)

Drug Name
Ketotifen
Synonyms
Ketotifen [INN:BAN]; Ketotifene; Ketotifene [INN-French]; Ketotifeno; Ketotifeno [INN-Spanish]; Ketotifenum; Ketotifenum [INN-Latin]; HC 20-511; ZCVMWBYGMWKGHF-UHFFFAOYSA-N; Zaditor; ketotifen; 34580-13-7; 4,9-Dihydro-4-(1-methyl-4-piperidinylidene)-10H-benzo(4,5)cyclohepta(1,2-b)thiophen-10-one; 4-(1-methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one; BRN 3983897; CHEMBL534; EINECS 252-099-7; HSDB 7283; UNII-X49220T18G
Indication
Disease Entry ICD 11 Status REF
Allergic conjunctivitis 9A60.02 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 309.4
Logarithm of the Partition Coefficient (xlogp) 3.2
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.25-2 h [2]
Bioavailability
The bioavailability of drug is 0.25-0.82% [2]
Elimination
More than 60% of an administered dose is excreted in the urine, primarily as metabolites - of this material, <1% is found as unchanged drug, while the glucuronide and pharmacologically active nor-ketotifen metabolites account for 50% and 10%, respectively [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 3 - 5 hours [4]
Metabolism
The drug is metabolized via several UGT enzymes [4]
Chemical Identifiers
Formula
C19H19NOS
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-8-one
Canonical SMILES
CN1CCC(=C2C3=C(C(=O)CC4=CC=CC=C42)SC=C3)CC1
InChI
ZCVMWBYGMWKGHF-UHFFFAOYSA-N
InChIKey
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
Cross-matching ID
PubChem CID
3827
ChEBI ID
CHEBI:92511
CAS Number
34580-13-7
DrugBank ID
DB00920
INTEDE ID
DR2514
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histamine H1 receptor (H1R) TTTIBOJ HRH1_HUMAN Antagonist [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Substrate []
UDP-glucuronosyltransferase 1A4 (UGT1A4) DELOY3P UD14_HUMAN Substrate []
UDP-glucuronosyltransferase 2B10 (UGT2B10) DEI8NGH UDB10_HUMAN Substrate []
Short-chain dehydrogenase/reductase SDR19C1 (DHRS1) DE1LZID DHRS1_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Gene/Protein Processing [7]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Allergic conjunctivitis
ICD Disease Classification 9A60.02
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Histamine H1 receptor (H1R) DTT HRH1 6.74E-01 0.13 0.43
Short-chain dehydrogenase/reductase SDR19C1 (DHRS1) DME DHRS1 8.83E-01 9.93E-03 2.54E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7206).
2 Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007;67(9):1343-57.
3 Health Canada Product Monograph: Zaditen (ketotifen fumarate) for oral administration
4 Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders. Drugs. 1990 Sep;40(3):412-48. doi: 10.2165/00003495-199040030-00006.
5 Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May;107(1):66-79.
6 Initial characterization of human DHRS1 (SDR19C1), a member of the short-chain dehydrogenase/reductase superfamily. J Steroid Biochem Mol Biol. 2019 Jan;185:80-89.
7 Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.