U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

CNS Activity

Curator's Comment: Hydroxytamoxifen is brain penetrant in animals. No human data available.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
The anti-estrogen hydroxytamoxifen is a potent antagonist in a novel yeast system.
1999 Nov
Differential activation of wild-type and variant forms of estrogen receptor alpha by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements.
2001 Jul
4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma.
2001 Jul 17
Cell response endpoints enhance sensitivity of the immature mouse uterotropic assay.
2001 May-Jun
Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor.
2002 Aug 1
The efficacy of endocrine disruptor screening tests in detecting anti-estrogenic effects downstream of receptor-ligand interactions.
2002 Jan 25
Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites.
2002 Oct
The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism.
2002 Oct
Comparison of the reporter gene assay for ER-alpha antagonists with the immature rat uterotrophic assay of 10 chemicals.
2003 Apr 30
Oestrogens and selective oestrogen receptor (ER) modulators regulate EGF receptor gene expression through human ER alpha and beta subtypes via an Sp1 site.
2003 Jul 31
Requirements for transcriptional regulation by the orphan nuclear receptor ERRgamma.
2004 Apr 30
Xenoestrogens and the induction of proliferative effects in breast cancer cells via direct activation of oestrogen receptor alpha.
2004 Feb
Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition.
2004 May 4
Inducible upregulation of oestrogen receptor-beta1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells.
2005 Apr
Selenium disrupts estrogen receptor (alpha) signaling and potentiates tamoxifen antagonism in endometrial cancer cells and tamoxifen-resistant breast cancer cells.
2005 Aug
CHIP (carboxyl terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha.
2005 Dec
Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR).
2005 Dec 1
Effects of prolonged tamoxifen treatment on receptor expression and apoptosis of ovarian cancer cells.
2005 Mar
Functional genomics may allow accurate categorization of the benzimidazole fungicide benomyl: lack of ability to act via steroid-receptor-mediated mechanisms.
2005 May 15
Estrogen-related receptors as emerging targets in cancer and metabolic disorders.
2006
Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells.
2006 Aug 1
Sulfotransferase (SULT) 1A1 polymorphic variants *1, *2, and *3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation.
2006 Jun
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.
2006 Nov
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Interplay between the levels of estrogen and estrogen receptor controls the level of the granzyme inhibitor, proteinase inhibitor 9 and susceptibility to immune surveillance by natural killer cells.
2007 Jun 14
Estrogen receptor-ligand complexes measured by chip-based nanoelectrospray mass spectrometry: an approach for the screening of endocrine disruptors.
2007 May
Regulation of growth hormone signaling by selective estrogen receptor modulators occurs through suppression of protein tyrosine phosphatases.
2007 May
Human CYP2A6 is induced by estrogen via estrogen receptor.
2007 Oct
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds.
2008 Jan
mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels.
2008 Oct
Regulation of the vascular endothelial growth factor and growth by estrogen and antiestrogens through Efp in Ishikawa endometrial carcinoma cells.
2009 Feb
Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer.
2009 Feb
Potential use of an estrogen-glucocorticoid receptor chimera as a drug screen for tissue selective estrogenic activity.
2009 Jan
The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells.
2009 Mar 1
Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF.
2009 Mar 4
Distinction of the binding modes for human nuclear receptor ERRgamma between bisphenol A and 4-hydroxytamoxifen.
2010 Aug
Optimization and prevalidation of the in vitro ERalpha CALUX method to test estrogenic and antiestrogenic activity of compounds.
2010 Aug
The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: results of test performance and transferability.
2010 Aug
c-Jun activation is required for 4-hydroxytamoxifen-induced cell death in breast cancer cells.
2010 Feb 18
Identification of novel ER-alpha target genes in breast cancer cells: gene- and cell-selective co-regulator recruitment at target promoters determines the response to 17beta-estradiol and tamoxifen.
2010 Jan 15
E-cadherin mediates the aggregation of breast cancer cells induced by tamoxifen and epidermal growth factor.
2010 May
Estrogen and selective estrogen receptor modulators regulate vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in human endometrial stromal cells.
2010 May 15
Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling.
2010 Nov
High content imaging-based assay to classify estrogen receptor-α ligands based on defined mechanistic outcomes.
2011 May 15
Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells.
2012 Apr
Cloning of circadian rhythmic pathway genes and perturbation of oscillation patterns in endocrine disrupting chemicals (EDCs)-exposed mangrove killifish Kryptolebias marmoratus.
2014 Aug
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.
2014 Oct 1
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.
2015 Feb
Patents

Sample Use Guides

A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Premenopausal women aged at least 18 years experiencing moderate to severe symptoms were randomized to receive placebo, 2 mg, or 4 mg of Afimoxifene daily delivered as a transdermal hydroalcoholic gel for 4 menstrual cycles.
Route of Administration: Transdermal
Viability of T47D, MCF-7 and BT-474 cell lines to 4-hydroxytamoxifen was dependent of its dose, and IC50 values after 96 h of treatment were 4.2, 3.2 and 5.7 μM, respectively
Substance Class Mixture
Created
by admin
on Fri Dec 15 16:35:51 UTC 2023
Edited
by admin
on Fri Dec 15 16:35:51 UTC 2023
Record UNII
17197F0KYM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AFIMOXIFENE
INN   USAN  
USAN   INN  
Official Name English
4-OHT
Code English
4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol
Common Name English
PHENOL, 4-(1-(4-(2-(DIMETHYLAMINO)ETHOXY)PHENYL)-2-PHENYL-1-BUTENYL)-
Common Name English
AFIMOXIFENE [USAN]
Common Name English
TAMOGEL
Brand Name English
afimoxifene [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1821
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
Code System Code Type Description
INN
8742
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DRUG BANK
DB04468
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SMS_ID
300000034088
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EPA CompTox
DTXSID3037094
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CHEBI
44616
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
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WIKIPEDIA
AFIMOXIFENE
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
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ChEMBL
CHEMBL10041
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
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NCI_THESAURUS
C975
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
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USAN
RR-104
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
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FDA UNII
17197F0KYM
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
PRIMARY
CAS
68392-35-8
Created by admin on Fri Dec 15 16:35:51 UTC 2023 , Edited by admin on Fri Dec 15 16:35:51 UTC 2023
PRIMARY
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Definition References