You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:09 UTC
HMDB IDHMDB14813
Secondary Accession NumbersNone
Metabolite Identification
Common NameTamoxifen
DescriptionTamoxifen is only found in individuals that have used or taken this drug. It is one of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. [PubChem]Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
Structure
Thumb
Synonyms
ValueSource
(Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamineChEBI
(Z)-2-(Para-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethylamineChEBI
1-P-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneChEBI
1-Para-beta-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneChEBI
apo-TamoxChEBI
CitofenChEBI
CrisafenoChEBI
DiemonChEBI
Gen-tamoxifenChEBI
IstubolChEBI
NoltamChEBI
NourytamChEBI
OncomoxChEBI
RetaximChEBI
TamofenChEBI
TamoneChEBI
TamoxastaChEBI
TamoxifeneChEBI
TamoxifenoChEBI
TamoxifenumChEBI
trans-TamoxifenChEBI
ValodexChEBI
ZemideChEBI
1-P-b-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneGenerator
1-P-β-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneGenerator
1-Para-b-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneGenerator
1-Para-β-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-eneGenerator
Tamoxifen citrateHMDB
Chemical FormulaC26H29NO
Average Molecular Weight371.5146
Monoisotopic Molecular Weight371.224914555
IUPAC Name(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
Traditional Nametamoxifen
CAS Registry Number10540-29-1
SMILES
CC\C(=C(/C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1
InChI Identifier
InChI=1S/C26H29NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18H,4,19-20H2,1-3H3/b26-25-
InChI KeyInChIKey=NKANXQFJJICGDU-QPLCGJKRSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassStilbenes
Sub ClassNot Available
Direct ParentStilbenes
Alternative Parents
Substituents
  • Stilbene
  • Diphenylmethane
  • Phenylpropene
  • Phenylpropane
  • Phenol ether
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents, Hormonal
  • Bone Density Conservation Agents
  • Estrogen Antagonists
  • Selective Estrogen Receptor Modulators
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point97 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.02e-03 g/LNot Available
LogP7.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.001 mg/mLALOGPS
logP5.93ALOGPS
logP6.35ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity128.43 m3·mol-1ChemAxon
Polarizability44.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Tamoxifen Metabolism PathwaySMP00606Not Available
Tamoxifen PathwaySMP00471Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00675
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00675
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00675
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2015313
KEGG Compound IDC07108
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTamoxifen
NuGOwiki LinkHMDB14813
Metagene LinkHMDB14813
METLIN IDNot Available
PubChem Compound2733526
PDB IDCTX
ChEBI ID41774
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Jordan VC: Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol. 1993 Oct;110(2):507-17. [8242225 ]
  2. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [15639680 ]
  3. Steiner AZ, Terplan M, Paulson RJ: Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005 Jun;20(6):1511-5. Epub 2005 Apr 21. [15845599 ]
  4. Jordan VC: Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol. 2006 Jan;147 Suppl 1:S269-76. [16402113 ]
  5. van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG: Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis. Ann Intern Med. 2006 Jan 17;144(2):101-6. [16418409 ]
  6. Graumann K, Jungbauer A: Agonistic and synergistic activity of tamoxifen in a yeast model system. Biochem Pharmacol. 2000 Jan 15;59(2):177-85. [10810452 ]
  7. FDA label

Enzymes

General function:
Involved in flavin-containing monooxygenase activity
Specific function:
In contrast with other forms of FMO it does not seem to be a drug-metabolizing enzyme.
Gene Name:
FMO5
Uniprot ID:
P49326
Molecular weight:
32480.04
Reactions
Tamoxifen + Oxygen + NADPH + Hydrogen Ion → Tamoxifen N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
Catalyzes the N-oxidation of certain primary alkylamines to their oximes via an N-hydroxylamine intermediate. Inactive toward certain tertiary amines, such as imipramine or chloropromazine. Can catalyze the S-oxidation of methimazole. The truncated form is catalytically inactive.
Gene Name:
FMO2
Uniprot ID:
Q99518
Molecular weight:
53643.29
Reactions
Tamoxifen + Oxygen + NADPH + Hydrogen Ion → Tamoxifen N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.
Gene Name:
FMO4
Uniprot ID:
P31512
Molecular weight:
63342.055
Reactions
Tamoxifen + Oxygen + NADPH + Hydrogen Ion → Tamoxifen N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds.
Gene Name:
FMO3
Uniprot ID:
P31513
Molecular weight:
60032.975
Reactions
Tamoxifen + Oxygen + NADPH + Hydrogen Ion → Tamoxifen N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name:
FMO1
Uniprot ID:
Q01740
Molecular weight:
60310.285
Reactions
Tamoxifen + Oxygen + NADPH + Hydrogen Ion → Tamoxifen N-oxide + NADP + Waterdetails