Substance
ID:558
Names and Identifiers
IUPAC Traditional name
tamoxifen
IUPAC name
(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
Brand Name
CrisafenoDiemonGen-TamoxifenNolvadexTamofenTamoneTamoxastaValodexCitofenNolvadex-DPMS-TamoxifenRetaximTamizamNovo-TamoxifenTamoxenIstubolOncomoxZemideApo-TamoxKessarNoltamNourytam
Synonyms
Tamoxifeno [INN-Spanish]Tamoxifenum [INN-Latin]TamoxifenTamoxifene [INN-French]Trans-TamoxifenTamoxifen Citrate
Properties
Physical Property
Hydrophobicity(logP)
7.1
Solubility
0.000167 mg/mL at 25 oC [MEYLAN,WM et al. (1996)]
Molecule Details
Drug Groups
approved
Description
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]
Indication
For the treatment of breast cancer.
Pharmacology
Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity.
Toxicity
Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
Affected Organisms
Humans and other mammals
Biotransformation
Hepatic. Tamoxifen is extensively metabolized after oral administration. N-Desmethyl-tamoxifen is the major metabolite found in plasma. N-Desmethyl-tamoxifen activity is similar to tamoxifen. 4-hydroxy-tamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. 4-Hydroxy-tamoxifen formation is catalyzed mainly by cytochrome P450 (CYP) 2D6, and also by CYP2C9 and 3A4. At high tamoxifen concentrations, CYP2B6 also catalyzes 4-hydroxylation of the parent drug. 4-Hydroxy-tamoxifen possesses 30- to 100-times greater affinity for the estrogen receptor and 30- to 100-times greater potency at inhibiting estrogen-dependent cell proliferation compared to tamoxifen.
Half Life
Distribution t1/2=7 to 14 hours; Elimination t1/2=5 to 7 days; Elimination t1/2 of N-desmethyl-tamoxifen=9-14 days.
Elimination
The drug is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
References
•
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.
[Pubmed]
•
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.
[Pubmed]
•
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.
[Pubmed]
•
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.
[Pubmed]
•
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.
[Pubmed]
External Links
Molecular Spectra
No Data Available
Click here to submit data
References
• 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. Pubmed
• 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. Pubmed
• 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. Pubmed
• 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. Pubmed
• 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. Pubmed