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Details

Stereochemistry ACHIRAL
Molecular Formula C26H29NO
Molecular Weight 371.5146
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TAMOXIFEN

SMILES

CC\C(C1=CC=CC=C1)=C(/C2=CC=CC=C2)C3=CC=C(OCCN(C)C)C=C3

InChI

InChIKey=NKANXQFJJICGDU-QPLCGJKRSA-N
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-

HIDE SMILES / InChI

Description

Tamoxifen (brand name Nolvadex), is selective estrogen receptor modulators (SERM) with tissue-specific activities for the treatment and prevention of estrogen receptor positive breast cancer. Tamoxifen itself is a prodrug, having relatively little affinity for its target protein, the estrogen receptor (ER). It is metabolized in the liver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen (4-OHT) (afimoxifene) and N-desmethyl-4-hydroxytamoxifen (endoxifen) which have 30–100 times more affinity with the ER than tamoxifen itself. These active metabolites compete with estrogen in the body for binding to the ER. In breast tissue, 4-OHT acts as an ER antagonist so that transcription of estrogen-responsive genes is inhibited. Tamoxifen has 7% and 6% of the affinity of estradiol for the ERα and ERβ, respectively, whereas 4-OHT has 178% and 338% of the affinity of estradiol for the ERα and ERβ. 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. Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER)-positive (ER+) breast cancer in pre- and post-menopausal women. Additionally, it is the most common hormone treatment for male breast cancer. Patients with variant forms of the gene CYP2D6 (also called simply 2D6) may not receive full benefit from tamoxifen because of too slow metabolism of the tamoxifen prodrug into its active metabolites. Tamoxifen is used as a research tool to trigger tissue-specific gene expression in many conditional expression constructs in genetically modified animals including a version of the Cre-Lox recombination technique. Tamoxifen has been shown to be effective in the treatment of mania in patients with bipolar disorder by blocking protein kinase C (PKC), an enzyme that regulates neuron activity in the brain. Researchers believe PKC is over-active during the mania in bipolar patients.

CNS Activity

Approval Year

PubMed

PubMed

TitleDatePubMed
[How I manage patients developing thromboembolic complications as a result of breast cancer treatment with tamoxifen ].
2002 Dec
Serum leptin levels are associated with tamoxifen-induced hepatic steatosis.
2003
Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites.
2003 Apr
Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand.
2003 Apr
Effects of a diphenyl ether-type herbicide, chlornitrofen, and its amino derivative on androgen and estrogen receptor activities.
2003 Apr
Tamoxifen and gallstone formation in postmenopausal breast cancer patients: retrospective cohort study.
2003 Apr
Comparison of the reporter gene assay for ER-alpha antagonists with the immature rat uterotrophic assay of 10 chemicals.
2003 Apr 30
Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 actions in human breast cancer cells.
2003 Feb
Cell proliferation, apoptosis, and expression of cyclin D1 and cyclin E as potential biomarkers in tamoxifen-treated mammary tumors.
2003 Feb
Inhibition of TNF-alpha-induced RANTES expression in human hepatocyte-derived cells by fibrates, the hypolipidemic drugs.
2003 Feb
The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen.
2003 Mar-Apr
Extensive pelvic endometriosis with malignant change in tamoxifen-treated postmenopausal women.
2003 May-Jun
Patents

Sample Use Guides

In Vivo Use Guide
For patients with breast cancer, the recommended daily dose is 20-40 mg. Dosages greater than 20 mg per day should be given in divided doses (morning and evening).
Route of Administration: Oral
In Vitro Use Guide
HELNalpha and HELNbeta two human cervix adenocarcinoma cell lines derived from HeLa cells stably transfected with the reporter gene ERE-betaGlob-Luc-SVNeo and the expression plasmids ERalpha or ERbeta respectively, were used to quantify the antiestrogenic and estrogenic effects of Tamoxifen. These cells were routinely cultivated in DMEM phenol red free, supplemented with 5% sFBS, 2 mM glutamine, 1% penicillin/streptomycin, 1 mg/mL Geneticin, and 0.5 mkg/mL puromycin to ensure appropriate antibiotic selection. For the assay, cells were trypsinized from the maintenance flask with phenol red free trypsin (0.05%)-EDTA (0.02%) (HyClone, Logan, UT) and seeded in an opaque 96-well plate (Nunc) at a density of 7.5 x 10^4 cells/well in a final volume of 100 mkL of assay medium (DMEM, phenol red free, supplemented with 3% sFBS, 2 mM glutamine, and penicillin/streptomycin). Five hours later, cells were adherent. Serial dilutions of Tamoxifen or DMSO as diluent control were then added in the presence of a fixed concentration of 17beta-estradiol (10^-10 M in HELNalpha and 10^-9 M in HELNbeta) to triplicate microcultures. Faslodex (Tocris, 10^-8 M) was used as a baseline indicator. Cells were incubated for 20 h at 37 °C in a 5% CO2 humidified incubator before being processed for luciferase determination. Medium was aspirated and 100 mkL of a 1:1 mixture of LucLite (Perkin-Elmer, Life Science, Boston, MA)/assay medium was added to each well. Plates were then sealed with a Topseal and left in the dark for 10 min before luminescence activity was determined by counting the plates for 6 s in a beta-TopCount (Packard Instrument Company, Meriden, CT).
Name Type Language
TAMOXIFEN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
TAMOXIFEN [HSDB]
Common Name English
TAMOPLEX
Brand Name English
ICI-47699
Code English
TAMOXIFEN [WHO-DD]
Common Name English
TAMOXIFEN [INN]
Common Name English
NOVALDEX
Brand Name English
(Z)-2-(4-(1,2-DIPHENYL-1-BUTENYL)PHENOXY)-N,N-DIMETHYLETHANAMINE
Systematic Name English
ETHANAMINE, 2-(4-((1Z)-1,2-DIPHENYL-1-BUTEN-1-YL)PHENOXY)-N,N-DIMETHYL-
Systematic Name English
TAMOXIFEN [VANDF]
Common Name English
MAMMATON
Brand Name English
TAMOXIFEN [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC L02BA01
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
LIVERTOX 921
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
WHO-ESSENTIAL MEDICINES LIST 8.3
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
NDF-RT N0000175826
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
NDF-RT N0000000168
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
WHO-VATC QL02BA01
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
Code System Code Type Description
MERCK INDEX
M10450
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY Merck Index
HSDB
10540-29-1
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
INN
3299
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
EVMPD
SUB10825MIG
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
RXCUI
10324
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY RxNorm
EPA CompTox
10540-29-1
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
MESH
D013629
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
DRUG BANK
DB00675
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
CAS
10540-29-1
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
WIKIPEDIA
TAMOXIFEN
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
ECHA (EC/EINECS)
234-118-0
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
LactMed
10540-29-1
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
PUBCHEM
2733526
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY SWITZERF
IUPHAR
1016
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
ChEMBL
CHEMBL83
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY
NCI_THESAURUS
C62078
Created by admin on Tue Mar 06 10:25:14 UTC 2018 , Edited by admin on Tue Mar 06 10:25:14 UTC 2018
PRIMARY