Tamoxifen metabolism (WP691)

Tamoxifen (TMX), sold under the brand name Nolvadex among others, is a medication that is used to prevent breast cancer in women and treat breast cancer in women and men.[1] It is also being studied for other types of cancer[1]. 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[2]. Additionally, it is the most common hormone treatment for male breast cancer. [1]: https://www.cancer.gov/about-cancer/treatment/drugs/tamoxifencitrate [2]: Jordan, V. Craig. "A current view of tamoxifen for the treatment and prevention of breast cancer." British journal of pharmacology 110.2 (1993): 507-517.
last edited

Authors

Pieter Giesbertz, MaintBot, Khanspers, Egonw, Ddigles, Zari, and DeSl

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: xenobiotic metabolic pathway breast cancer pathway

Disease Ontology: estrogen-receptor positive breast cancer

Participants

Label Type Compact Identifier
Tamoxifen-N-oxide Metabolite pubchem.compound:3033895
CYP2D6 GeneProduct ensembl:ENSG00000100197
cis-4-hydroxytamoxifen Metabolite pubchem.compound:449459
SSRI Metabolite chebi:50949
trans-4-hydroxytamoxifen-N-glucuronide Metabolite None
alpha-hydroxy-N-desmethyltamoxifen Metabolite pubchem.compound:10474509
PAP Metabolite hmdb:HMDB0000061
PAP Metabolite hmdb:HMDB0000061
CYP2A6 GeneProduct ensembl:ENSG00000255974
cis-4-hydroxy-N-desmethyltamoxifen Metabolite None
SULT2A1 GeneProduct ensembl:ENSG00000105398
CYP2C9 GeneProduct ensembl:ENSG00000138109
tamoxifen-N-glucuronide Metabolite pubchem.compound:5460873
CYP3A5 GeneProduct ensembl:ENSG00000106258
CYP2C19 GeneProduct ensembl:ENSG00000165841
CYP3A4 GeneProduct ensembl:ENSG00000160868
PAPS Metabolite pubchem.compound:10214
CYP3A4 GeneProduct ensembl:ENSG00000160868
UGT1A10 GeneProduct ncbigene:54575
CYP3A4 GeneProduct ensembl:ENSG00000160868
trans-4-Sulfoxytamoxifen Metabolite None
SULT2A1 GeneProduct ensembl:ENSG00000105398
SULT2A1 GeneProduct ensembl:ENSG00000105398
CYP1A2 GeneProduct ensembl:ENSG00000140505
CYP3A4 GeneProduct ensembl:ENSG00000160868
UGT2B7 GeneProduct ncbigene:7364
PAPS Metabolite pubchem.compound:10214
CYP2D6 GeneProduct ensembl:ENSG00000100197
4-hydroxy-N-desmethyltamoxifen Metabolite pubchem.compound:3035980
trans-tamoxifen Metabolite hmdb:HMDB0014813
SULT1E1 GeneProduct ensembl:ENSG00000109193
SULT1A1 GeneProduct ensembl:ENSG00000196502
FMO1 GeneProduct ensembl:ENSG00000010932
CYP2C9 GeneProduct ensembl:ENSG00000138109
CYP2E1 GeneProduct ensembl:ENSG00000130649
SULT1A1 GeneProduct ensembl:ENSG00000196502
FMO3 GeneProduct ensembl:ENSG00000007933
SULT1E1 GeneProduct ensembl:ENSG00000109193
CYP3A4 GeneProduct ensembl:ENSG00000160868
UGT1A4 GeneProduct ncbigene:54657
CYP3A5 GeneProduct ensembl:ENSG00000106258
deamino-hydroxytamoxifen Metabolite pubchem.compound:3033897
alpha-hydroxytamoxifen Metabolite hmdb:HMDB0060585
CYP2C19 GeneProduct ensembl:ENSG00000165841
UGT1A4 GeneProduct ncbigene:54657
CYP1B1 GeneProduct ensembl:ENSG00000138061
trans-4-Sulfoxytamoxifen Metabolite None
N,N-didesmethyltamoxifen Metabolite pubchem.compound:3036172
UGT1A4 GeneProduct ncbigene:54657
Metabolite Metabolite chebi:25212
UGT1A8 GeneProduct ncbigene:54576
cis-4-hydroxytamoxifen-N-glucuronide Metabolite None
cis-tamoxifen-4-O-glucuronide Metabolite None
CYP2C19 GeneProduct ensembl:ENSG00000165841
CYP3A4 GeneProduct ensembl:ENSG00000160868
trans-tamoxifen-4-O-glucuronide Metabolite None
trans-N-desmethyltamoxifen-O-glucuronide Metabolite None
CYP2D6 GeneProduct ensembl:ENSG00000100197
trans-4-hydroxytamoxifen Metabolite pubchem.compound:5352135
CYP1A1 GeneProduct ensembl:ENSG00000140465
N-desmethyltamoxifen Metabolite pubchem.compound:3032890
cis-N-desmethyltamoxifen-O-glucuronide Metabolite None
CYP2D6 GeneProduct ensembl:ENSG00000100197
CYP2C8 GeneProduct ensembl:ENSG00000138115
UGT2B15 GeneProduct ensembl:ENSG00000196620
CYP3A4 GeneProduct ensembl:ENSG00000160868

References

  1. Kaku T, Ogura K, Nishiyama T, Ohnuma T, Muro K, Hiratsuka A. Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol. 2004 Jun 1;67(11):2093–102. PubMed Europe PMC Scholia
  2. Ogura K, Ishikawa Y, Kaku T, Nishiyama T, Ohnuma T, Muro K, et al. Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol. 2006 Apr 28;71(9):1358–69. PubMed Europe PMC Scholia
  3. Jordan VC. Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer. 2007 Jan;7(1):46–53. PubMed Europe PMC Scholia
  4. Jordan VC. New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer. Steroids. 2007 Nov;72(13):829–42. PubMed Europe PMC Scholia
  5. Lazarus P, Blevins-Primeau AS, Zheng Y, Sun D. Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen. Ann N Y Acad Sci. 2009 Feb;1155:99–111. PubMed Europe PMC Scholia