CHEBI:44616 - afimoxifene

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ChEBI Name afimoxifene
ChEBI ID CHEBI:44616
Definition A tertiary amino compound that is tamoxifen in which the phenyl group which is in a Z- relationship to the ethyl substituent is hydroxylated at the para- position. It is the active metabolite of tamoxifen.
Stars This entity has been manually annotated by the ChEBI Team.
Supplier Information eMolecules:539295, ZINC000000902197
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Afimoxifene, also known as 4-hydroxytamoxifen (4-OHT) and by its tentative brand name TamoGel, is a selective estrogen receptor modulator (SERM) of the triphenylethylene group and an active metabolite of tamoxifen. The drug is under development under the tentative brand name TamoGel as a topical gel for the treatment of hyperplasia of the breast. It has completed a phase II clinical trial for cyclical mastalgia, but further studies are required before afimoxifene can be approved for this indication and marketed. Afimoxifene is a SERM and hence acts as a tissue-selective agonist–antagonist of the estrogen receptors ERα and ERβ with mixed estrogenic and antiestrogenic activity depending on the tissue. It is also an agonist of the G protein-coupled estrogen receptor (GPER) with relatively low affinity (100–1,000 nM, relative to 3–6 nM for estradiol). In addition to its estrogenic and antiestrogenic activity, afimoxifene has been found to act as an antagonist of the estrogen-related receptors (ERRs) ERRβ and ERRγ.
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Formula C26H29NO2
Net Charge 0
Average Mass 387.51400
Monoisotopic Mass 387.21983
InChI InChI=1S/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-
InChIKey TXUZVZSFRXZGTL-QPLCGJKRSA-N
SMILES CC\C(c1ccccc1)=C(/c1ccc(O)cc1)c1ccc(OCCN(C)C)cc1
Roles Classification
Chemical Role(s): Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Biological Role(s): estrogen receptor antagonist
An antagonist at the estrogen receptor.
metabolite
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
Application(s): antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
estrogen receptor antagonist
An antagonist at the estrogen receptor.
View more via ChEBI Ontology
ChEBI Ontology
Outgoing afimoxifene (CHEBI:44616) has functional parent tamoxifen (CHEBI:41774)
afimoxifene (CHEBI:44616) has role antineoplastic agent (CHEBI:35610)
afimoxifene (CHEBI:44616) has role estrogen receptor antagonist (CHEBI:50792)
afimoxifene (CHEBI:44616) has role metabolite (CHEBI:25212)
afimoxifene (CHEBI:44616) is a phenols (CHEBI:33853)
afimoxifene (CHEBI:44616) is a tertiary amino compound (CHEBI:50996)
INN Source
afimoxifene ChemIDplus
Synonyms Sources
4-HYDROXYTAMOXIFEN PDBeChem
4-Hydroxytamoxifen KEGG COMPOUND
4-hydroxytamoxifen ChemIDplus
4-monohydroxytamoxifen ChEBI
4-OHT ChemIDplus
Manual Xrefs Databases
Afimoxifene Wikipedia
C05011 KEGG COMPOUND
D06551 KEGG DRUG
OHT PDBeChem
View more database links
Registry Numbers Types Sources
4910748 Reaxys Registry Number Reaxys
68047-06-3 CAS Registry Number KEGG COMPOUND
68392-35-8 CAS Registry Number ChemIDplus
Citations
Lin HY, Han HW, Wang YS, He DL, Sun WX, Feng L, Wen ZL, Yang MK, Lu GH, Wang XM, Qi JL, Yang YH (2020)
Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo.
Chinese medicine 15, 23 [PubMed:32175001]
[show Abstract]
Almomen A, Maher HM, Alzoman NZ, Shehata SM, Al-Taweel SM, Alanazi AA (2020)
Development and validation of UPLC-MS/MS method for studying the pharmacokinetic interaction of dasabuvir and tamoxifen, 4-hydroxytamoxifen in Wistar rats.
Scientific reports 10, 3521 [PubMed:32103133]
[show Abstract]
Wang G, Qin S, Zayas J, Ingle JN, Liu M, Weinshilboum RM, Shen K, Wang L (2019)
4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion.
Breast cancer research and treatment 175, 567-578 [PubMed:30937657]
[show Abstract]
Liu X, Miao W, Huang M, Li L, Dai X, Wang Y (2019)
Elevated Hexokinase II Expression Confers Acquired Resistance to 4-Hydroxytamoxifen in Breast Cancer Cells.
Molecular & cellular proteomics : MCP 18, 2273-2284 [PubMed:31519767]
[show Abstract]
Sundralingam U, Khan TM, Elendran S, Muniyandy S, Palanisamy UD (2019)
Review: Patient-controlled transdermal 4-hydroxytamoxifen (4-OHT) vs. oral tamoxifen: A systematic review and meta analysis.
Pakistan journal of pharmaceutical sciences 32, 1121-1128 [PubMed:31278729]
[show Abstract]
Chao TC, Pan WC, Tsai YF, Chou YC, Liu YR, Wang SF, Chen YJ, Souček P, Ueng YF (2019)
Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol.
Toxicology and applied pharmacology 378, 114619 [PubMed:31195002]
[show Abstract]
Ota Y, Itoh Y, Kaise A, Ohta K, Endo Y, Masuda M, Sowa Y, Sakai T, Suzuki T (2016)
Targeting Cancer with PCPA-Drug Conjugates: LSD1 Inhibition-Triggered Release of 4-Hydroxytamoxifen.
Angewandte Chemie (International ed. in English) 55, 16115-16118 [PubMed:27882656]
[show Abstract]
Zhong Q, Zhang C, Zhang Q, Miele L, Zheng S, Wang G (2015)
Boronic prodrug of 4-hydroxytamoxifen is more efficacious than tamoxifen with enhanced bioavailability independent of CYP2D6 status.
BMC cancer 15, 625 [PubMed:26354796]
[show Abstract]
Jager NG, Rosing H, Linn SC, Schellens JH, Beijnen JH (2012)
Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.
Breast cancer research and treatment 133, 793-798 [PubMed:22388692]
[show Abstract]
El Gebeily G, Fiset C (2010)
4-Hydroxytamoxifen inhibits K(+) currents in mouse ventricular myocytes.
European journal of pharmacology 629, 96-103 [PubMed:20006599]
[show Abstract]
Mansel R, Goyal A, Nestour EL, Masini-Etévé V, O'Connell K, Afimoxifene (4-OHT) Breast Pain Research Group (2007)
A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women.
Breast cancer research and treatment 106, 389-397 [PubMed:17351746]
[show Abstract]
Desta Z, Ward BA, Soukhova NV, Flockhart DA (2004)
Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6.
The Journal of pharmacology and experimental therapeutics 310, 1062-1075 [PubMed:15159443]
[show Abstract]
Cardoso CM, Almeida LM, Custódio JB (2002)
4-Hydroxytamoxifen is a potent inhibitor of the mitochondrial permeability transition.
Mitochondrion 1, 485-495 [PubMed:16120301]
[show Abstract]
Last Modified
05 June 2020