Page last updated: 2024-12-05

nafoxidine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Nafoxidine: An estrogen antagonist that has been used in the treatment of breast cancer. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID4416
CHEMBL ID28211
CHEBI ID34881
SCHEMBL ID153125
MeSH IDM0014421

Synonyms (40)

Synonym
BIDD:ER0063
nafoxidinum [inn-latin]
nsc 70735
nafoxidine [inn]
brn 1440873
pyrrolidine, 1-(2-(p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy)ethyl)-
nafoxidina [inn-spanish]
pyrrolidine, 1-(2-(4-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl)phenoxy)ethyl)-
u-11000a
1-(2-(p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy)ethyl)pyrrolidine
1845-11-0
nafoxidine
SPECTRUM5_000222
1-[2-[4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine
11100a (*hydrochloride*)
nsc70735
u 11100a (*hydrochloride*)
u-11100a (*hydrochloride*)
u 11100 (*hydrochloride*)
1-{2-[4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine
CHEMBL28211 ,
chebi:34881 ,
1-{2-[4-(6-methoxy-2-phenyl-3,4-dihydro-naphthalen-1-yl)-phenoxy]-ethyl}-pyrrolidine
bdbm50065941
NCGC00188970-01
nafoxidina
4riy10wm82 ,
5-20-01-00210 (beilstein handbook reference)
nafoxidinum
unii-4riy10wm82
gtpl4263
nafoxidine [who-dd]
SCHEMBL153125
1-(2-(4-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl)phenoxy)ethyl)pyrrolidine
1-(2-[4-(6-methoxy-2-phenyl-3,4-dihydro-1-naphthalenyl)phenoxy]ethyl)pyrrolidine #
DTXSID7022386
Q6958201
pyrrolidine,1-[2-[4-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl)phenoxy]ethyl]-
1-(2-(4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy)ethyl)pyrrolidine
AKOS040744832

Research Excerpts

Overview

Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the National Cancer Institute. It acts as an estrogen agonist or antagonist depending on the animal model used.

ExcerptReferenceRelevance
"Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. "( Nafoxidine--an antiestrogen for the treatment of breast cancer.
Carter, SK; Legha, SS; Slavik, M, 1976
)
3.14
"Nafoxidine (NAF) acts as an estrogen agonist or antagonist depending on the animal model used. "( Response of the mouse uterus to nafoxidine stimulation: agonism and antagonism.
Fox-Davies, C; Korach, KS; Newbold, RR; Quarmby, VE, 1988
)
2

Treatment

Nafoxidine treatment not only arrested the development of the mammary glands in female GR mice (causing them to appear "masculinized") but it also produced abnormalities within the glands. In naf Oxidine-treated OVX rats, concurrent progesterone administration had no effect on adipose tissue LPL activity, but progester one did increase food intake, body weight, and carcass fat content.

ExcerptReferenceRelevance
"Thus Nafoxidine treatment not only arrested the development of the mammary glands in female GR mice (causing them to appear "masculinized") but it also produced abnormalities within the glands."( Nafoxidine administered to newborn female GR mice arrests the development of their mammary glands.
Strum, JM, 1983
)
2.16
"In nafoxidine-treated OVX rats, concurrent progesterone administration had no effect on adipose tissue LPL activity, but progesterone did increase food intake, body weight, and carcass fat content."( Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens.
Gray, JM; Wade, GN, 1981
)
0.78
"Pretreatment with nafoxidine was less effective."( Effect of nafoxidine (U-11,100A) on the induction of uterine peroxidase.
Jellinck, PH; McNabb, T, 1976
)
0.98

Dosage Studied

ExcerptRelevanceReference
" A correlation between the levels of nuclear [3H]-estradiol binding at 24 hr and phosphoprotein at 48 hr is shown in a dose-response experiment."( (3H)-estradiol binding by chick liver nuclear extracts: mechanism of increase in binding following estradiol injection.
Lazier, C, 1975
)
0.25
" The effect of varying the dosage of injected E2 (0."( Different nuclear binding sites for antiestrogen and estrogen receptor complexes.
Baudendistel, LJ; Ruh, TS, 1977
)
0.26
" Hence, in these studies, we compare the action of a long-acting estrogen (17alpha-ethinyl estriol-3-cyclopentyl ether, EE3CPE) and a long-acting antiestrogen (U-11,100AUA) on the immature rat uterus and analyze different dosage regimens (single and multiple injections) in studying the effects of these compounds on the uterine estrogen receptor and on uterine growth and sensitivity to estradiol."( Fundamental differences in the action of estrogens and antiestrogens on the uterus: comparison between compounds with similar duration of action.
Ferguson, ER; Katzenellenbogen, BS; Lan, NC, 1977
)
0.26
" Five weeks of oral dosing confirmed that ethynyl estradiol, tamoxifen, and raloxifene are potent inhibitors of the loss in volumetric bone mineral density (BMD, mg/cc) induced by ovariectomy, as measured by computed tomography."( Raloxifene, tamoxifen, nafoxidine, or estrogen effects on reproductive and nonreproductive tissues in ovariectomized rats.
Bryant, HU; Rippy, MK; Sato, M, 1996
)
0.6
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (3)

ClassDescription
naphthalenesAny benzenoid aromatic compound having a skeleton composed of two ortho-fused benzene rings.
ring assemblyTwo or more cyclic systems (single rings or fused systems) which are directly joined to each other by double or single bonds are named ring assemblies when the number of such direct ring junctions is one less than the number of cyclic systems involved.
benzenesAny benzenoid aromatic compound consisting of the benzene skeleton and its substituted derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Estrogen receptorRattus norvegicus (Norway rat)IC50 (µMol)0.04090.00074.152114.1600AID69383
Androgen receptorRattus norvegicus (Norway rat)IC50 (µMol)12.88250.00101.979414.1600AID255211
C-8 sterol isomeraseSaccharomyces cerevisiae S288CKi0.23200.00000.90487.1500AID239296
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)Ki0.00090.00040.54906.7000AID239597
Estrogen receptor betaRattus norvegicus (Norway rat)IC50 (µMol)0.04090.00124.765214.1600AID69383
Sigma non-opioid intracellular receptor 1Homo sapiens (human)Ki0.03000.00000.490110.0000AID239347
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (11)

Processvia Protein(s)Taxonomy
cholesterol biosynthetic process3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
cholesterol metabolic process3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
hemopoiesis3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
cholesterol biosynthetic process via desmosterol3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
cholesterol biosynthetic process via lathosterol3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
ossification involved in bone maturation3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
lipid transportSigma non-opioid intracellular receptor 1Homo sapiens (human)
nervous system developmentSigma non-opioid intracellular receptor 1Homo sapiens (human)
G protein-coupled opioid receptor signaling pathwaySigma non-opioid intracellular receptor 1Homo sapiens (human)
regulation of neuron apoptotic processSigma non-opioid intracellular receptor 1Homo sapiens (human)
protein homotrimerizationSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
C-8 sterol isomerase activity3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
steroid delta-isomerase activity3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
protein binding3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
identical protein binding3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
cholestenol delta-isomerase activity3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
G protein-coupled opioid receptor activitySigma non-opioid intracellular receptor 1Homo sapiens (human)
protein bindingSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (14)

Processvia Protein(s)Taxonomy
nuclear envelope3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
endoplasmic reticulum3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
endoplasmic reticulum membrane3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
cytoplasmic vesicle3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
nuclear membrane3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
endoplasmic reticulum3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseHomo sapiens (human)
nuclear envelopeSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear inner membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear outer membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulum membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
lipid dropletSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytosolSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic densitySigma non-opioid intracellular receptor 1Homo sapiens (human)
membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
growth coneSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytoplasmic vesicleSigma non-opioid intracellular receptor 1Homo sapiens (human)
anchoring junctionSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic density membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (21)

Assay IDTitleYearJournalArticle
AID38613Relative binding affinity(RBA) against AEBS (Antiestrogen binding site) in guinea pig uterus1992Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8
Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis.
AID189169Relative binding affinity for uterine cytosolic estrogen receptors of immature rats1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Studies in antifertility agents. 50. Stereoselective binding of d- and l-centchromans to estrogen receptors and their antifertility activity.
AID195685Uterotrophic activity in rats relative to estradiol (E2 = 100%)1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Studies in antifertility agents. 50. Stereoselective binding of d- and l-centchromans to estrogen receptors and their antifertility activity.
AID69383Inhibition of estradiol binding to estrogen receptor1998Journal of medicinal chemistry, Jul-30, Volume: 41, Issue:16
Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene.
AID1676123Antiviral activity against pseudotyped Ebola virus - Zaire (1995) Kikwit infected in human A549 cells assessed as reduction in viral infection incubated for 24 hrs by Hoechst staining based fluorescence assay2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID183483Antiestrogenic potency was measured by inhibition of estrus in ovariectomized rats treated with 17-beta-estradiol at a dose of 0.5 mg1982Journal of medicinal chemistry, Mar, Volume: 25, Issue:3
Antiestrogenic properties of substituted benz[a]anthracene-3,9-diols.
AID239296Affinity for ERG2 of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine radioligand2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening.
AID226387Relative binding affinity(RBA) against AEBS (Antiestrogen binding site) in rat liver1992Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8
Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis.
AID255211Inhibitory concentration against recombinant rat androgen receptor expressed in Escherichia coli using [3H]methyltrienolone (R 1881)2005Journal of medicinal chemistry, Sep-08, Volume: 48, Issue:18
Impact of induced fit on ligand binding to the androgen receptor: a multidimensional QSAR study to predict endocrine-disrupting effects of environmental chemicals.
AID1676121Antiviral activity against pseudotyped Marburgvirus-Angola infected in human A549 cells assessed as reduction in viral infection incubated for 24 hrs by Hoechst staining based fluorescence assay2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID1676126Antiviral activity against pseudotyped Ebola virus - Mayinga, Zaire infected in human A549 cells assessed as reduction in viral infection incubated for 48 hrs by luciferase reporter gene assay2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID1676122Selectivity index, ratio of CC50 for human A549 cells to IC50 for antiviral activity against pseudotyped Ebola virus - Zaire (1995) Kikwit infected in human A549 cells2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID1676120Selectivity index, ratio of CC50 for human A549 cells to IC50 for antiviral activity against pseudotyped Marburgvirus-Angola infected in human A549 cells2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID38610Relative binding affinity(RBA) against AEBS (Antiestrogen binding site) in chicken liver1992Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8
Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis.
AID184492Antiimplantation activity in sperm-positive female albino rats mated to coeval males of proven fertility1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
Studies in antifertility agents. 50. Stereoselective binding of d- and l-centchromans to estrogen receptors and their antifertility activity.
AID1676127Antiviral activity against pseudotyped Marburgvirus-Musoke infected in human A549 cells assessed as reduction in viral infection incubated for 48 hrs by luciferase reporter gene assay2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID239597Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening.
AID239347Affinity for sigma receptor type 1 of guinea pig using [3H]ifenprodil or (+)-[3H]pentazocine radioligand2005Journal of medicinal chemistry, Jul-28, Volume: 48, Issue:15
Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening.
AID1676124Selectivity index, ratio of CC50 for human A549 cells to IC50 for antiviral activity against pseudotyped Marburgvirus-Musoke infected in human A549 cells2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID1676125Selectivity index, ratio of CC50 for human A549 cells to IC50 for antiviral activity against pseudotyped Ebola virus - Mayinga, Zaire infected in human A549 cells2020Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19
Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.
AID681359TP_TRANSPORTER: ATP hydrolysis in MDR1-expressing Sf9 cells1994Biochemical pharmacology, Jul-19, Volume: 48, Issue:2
Antiestrogens and steroid hormones: substrates of the human P-glycoprotein.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (230)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990195 (84.78)18.7374
1990's27 (11.74)18.2507
2000's5 (2.17)29.6817
2010's2 (0.87)24.3611
2020's1 (0.43)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 20.14

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index20.14 (24.57)
Research Supply Index5.53 (2.92)
Research Growth Index4.02 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (20.14)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (2.88%)5.53%
Reviews8 (3.29%)6.00%
Case Studies2 (0.82%)4.05%
Observational0 (0.00%)0.25%
Other226 (93.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]