Page last updated: 2024-11-06

4-methoxyestradiol

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

Description

4-Methoxyestradiol (4-OHE2) is a naturally occurring catechol estrogen metabolite. It is synthesized in the body from estradiol by the action of the enzyme catechol-O-methyltransferase (COMT). 4-OHE2 has been shown to have a wide range of biological effects, including anti-angiogenic, anti-proliferative, and apoptotic activities. It has been studied for its potential therapeutic applications in cancer, neurodegenerative diseases, and cardiovascular diseases. 4-OHE2 is also a potent inhibitor of the enzyme tyrosine kinase, which is involved in cell growth and proliferation. Its anti-angiogenic properties are attributed to its ability to inhibit the formation of new blood vessels, which are essential for tumor growth and metastasis. Its anti-proliferative activity stems from its ability to induce cell cycle arrest and apoptosis. Additionally, 4-OHE2 has shown neuroprotective effects in animal models of Parkinson's disease and Alzheimer's disease. Its importance lies in its potential as a therapeutic agent for a variety of diseases. Extensive research is ongoing to better understand its mechanisms of action and its potential clinical applications.'

4-methoxyestradiol: RN given refers to (17beta)-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

4-methoxy-17beta-estradiol : A 17beta-hydroxy steroid that is 17beta-estradiol in which the hydrogen at position 4 has been replaced by a methoxy group. [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]

Cross-References

ID SourceID
PubMed CID68578
CHEMBL ID4084860
CHEBI ID136975
SCHEMBL ID2596534
MeSH IDM0131129

Synonyms (27)

Synonym
(17beta)-4-methoxyestra-1,3,5(10)-triene-3,17-diol
4-methoxy-17beta-estradiol
4-meoe2
26788-23-8
4-methoxy-3,17beta-dihydroxy-1,3,5[10]-estratriene
CHEBI:136975
4-methoxyestradiol-17beta
4-methoxyestradiol
(8r,9s,13s,14s,17s)-4-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
r6yv5q2lks ,
estra-1,3,5(10)-triene-3,17-diol, 4-methoxy-, (17beta)-
unii-r6yv5q2lks
SCHEMBL2596534
4-methoxy-estradiol
4-methoxy-estra-1,3,5(10)-triene-3beta-ol
4-methoxy 17??-estradiol
AKOS027378613
3,4,17beta-trihydroxy-1,3,5[10]-estratriene 4-methyl ether
4-methoxy-1,3,5[10]-estratriene-3,17beta-diol
3,17beta-dihydroxy-4-methoxy-1,3,5[10]-estratriene
1,3,5(10)-estratrien-3,4,17beta-triol 4-methyl ether
bdbm50252402
4-methoxy 17beta-estradiol
CHEMBL4084860 ,
DTXSID50949596
4-methoxy 17?-estradiol
(1s,3as,3br,9bs,11as)-6-methoxy-11a-methyl-1h,2h,3h,3ah,3bh,4h,5h,9bh,10h,11h,11ah-cyclopenta[a]phenanthrene-1,7-diol

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"Interindividual differences in the bioavailability of potentially carcinogenic estrogen and estrogen metabolites (EMs) may play a role in the risk of breast cancer."( Dietary Fat and Fiber Intakes Are Not Associated with Patterns of Urinary Estrogen Metabolites in Premenopausal Women.
Eliassen, AH; Fuhrman, BJ; Hankinson, SE; Oh, H; Smith-Warner, SA; Tamimi, RM; Wang, M; Xu, X; Ziegler, RG, 2015
)
0.42
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
estrogenA hormone that stimulates or controls the development and maintenance of female sex characteristics in mammals by binding to oestrogen receptors. The oestrogens are named for their importance in the oestrous cycle. The oestrogens that occur naturally in the body, notably estrone, estradiol, estriol, and estetrol are steroids. Other compounds with oestrogenic activity are produced by plants (phytoestrogens) and fungi (mycoestrogens); synthetic compounds with oestrogenic activity are known as xenoestrogens.
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
rat metaboliteAny mammalian metabolite produced during a metabolic reaction in rat (Rattus norvegicus).
[role 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]

Drug Classes (4)

ClassDescription
17beta-hydroxy steroidA 17-hydroxy steroid in which the hydroxy group at position 17 has a beta-configuration.
3-hydroxy steroidAny hydroxy steroid carrying a hydroxy group at position 3.
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
phenolsOrganic aromatic compounds having one or more hydroxy groups attached to a benzene or other arene ring.
[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 (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Cytochrome P450 1A1Homo sapiens (human)Ki149.00000.01200.94693.8000AID1453015
Cytochrome P450 1B1Homo sapiens (human)Ki149.00000.00300.97417.4600AID1453015
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (88)

Processvia Protein(s)Taxonomy
cellular response to organic cyclic compoundCytochrome P450 1A1Homo sapiens (human)
response to hypoxiaCytochrome P450 1A1Homo sapiens (human)
long-chain fatty acid metabolic processCytochrome P450 1A1Homo sapiens (human)
lipid hydroxylationCytochrome P450 1A1Homo sapiens (human)
fatty acid metabolic processCytochrome P450 1A1Homo sapiens (human)
steroid biosynthetic processCytochrome P450 1A1Homo sapiens (human)
porphyrin-containing compound metabolic processCytochrome P450 1A1Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 1A1Homo sapiens (human)
steroid metabolic processCytochrome P450 1A1Homo sapiens (human)
estrogen metabolic processCytochrome P450 1A1Homo sapiens (human)
amine metabolic processCytochrome P450 1A1Homo sapiens (human)
response to nematodeCytochrome P450 1A1Homo sapiens (human)
response to herbicideCytochrome P450 1A1Homo sapiens (human)
ethylene metabolic processCytochrome P450 1A1Homo sapiens (human)
coumarin metabolic processCytochrome P450 1A1Homo sapiens (human)
flavonoid metabolic processCytochrome P450 1A1Homo sapiens (human)
response to iron(III) ionCytochrome P450 1A1Homo sapiens (human)
insecticide metabolic processCytochrome P450 1A1Homo sapiens (human)
dibenzo-p-dioxin catabolic processCytochrome P450 1A1Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 1A1Homo sapiens (human)
response to foodCytochrome P450 1A1Homo sapiens (human)
response to lipopolysaccharideCytochrome P450 1A1Homo sapiens (human)
response to vitamin ACytochrome P450 1A1Homo sapiens (human)
response to immobilization stressCytochrome P450 1A1Homo sapiens (human)
vitamin D metabolic processCytochrome P450 1A1Homo sapiens (human)
retinol metabolic processCytochrome P450 1A1Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 1A1Homo sapiens (human)
9-cis-retinoic acid biosynthetic processCytochrome P450 1A1Homo sapiens (human)
camera-type eye developmentCytochrome P450 1A1Homo sapiens (human)
nitric oxide metabolic processCytochrome P450 1A1Homo sapiens (human)
response to arsenic-containing substanceCytochrome P450 1A1Homo sapiens (human)
digestive tract developmentCytochrome P450 1A1Homo sapiens (human)
tissue remodelingCytochrome P450 1A1Homo sapiens (human)
hydrogen peroxide biosynthetic processCytochrome P450 1A1Homo sapiens (human)
response to hyperoxiaCytochrome P450 1A1Homo sapiens (human)
maternal process involved in parturitionCytochrome P450 1A1Homo sapiens (human)
hepatocyte differentiationCytochrome P450 1A1Homo sapiens (human)
cellular response to copper ionCytochrome P450 1A1Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 1A1Homo sapiens (human)
positive regulation of G1/S transition of mitotic cell cycleCytochrome P450 1A1Homo sapiens (human)
response to 3-methylcholanthreneCytochrome P450 1A1Homo sapiens (human)
cellular response to organic cyclic compoundCytochrome P450 1B1Homo sapiens (human)
angiogenesisCytochrome P450 1B1Homo sapiens (human)
trabecular meshwork developmentCytochrome P450 1B1Homo sapiens (human)
DNA modificationCytochrome P450 1B1Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 1B1Homo sapiens (human)
nitric oxide biosynthetic processCytochrome P450 1B1Homo sapiens (human)
cell adhesionCytochrome P450 1B1Homo sapiens (human)
response to nutrientCytochrome P450 1B1Homo sapiens (human)
steroid metabolic processCytochrome P450 1B1Homo sapiens (human)
estrogen metabolic processCytochrome P450 1B1Homo sapiens (human)
negative regulation of cell population proliferationCytochrome P450 1B1Homo sapiens (human)
male gonad developmentCytochrome P450 1B1Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to oxidative stressCytochrome P450 1B1Homo sapiens (human)
toxin metabolic processCytochrome P450 1B1Homo sapiens (human)
positive regulation of vascular endothelial growth factor productionCytochrome P450 1B1Homo sapiens (human)
positive regulation of smooth muscle cell migrationCytochrome P450 1B1Homo sapiens (human)
sterol metabolic processCytochrome P450 1B1Homo sapiens (human)
arachidonic acid metabolic processCytochrome P450 1B1Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 1B1Homo sapiens (human)
collagen fibril organizationCytochrome P450 1B1Homo sapiens (human)
adrenal gland developmentCytochrome P450 1B1Homo sapiens (human)
negative regulation of cell migrationCytochrome P450 1B1Homo sapiens (human)
negative regulation of NF-kappaB transcription factor activityCytochrome P450 1B1Homo sapiens (human)
response to follicle-stimulating hormoneCytochrome P450 1B1Homo sapiens (human)
response to estradiolCytochrome P450 1B1Homo sapiens (human)
negative regulation of cell adhesion mediated by integrinCytochrome P450 1B1Homo sapiens (human)
benzene-containing compound metabolic processCytochrome P450 1B1Homo sapiens (human)
retinol metabolic processCytochrome P450 1B1Homo sapiens (human)
retinal metabolic processCytochrome P450 1B1Homo sapiens (human)
positive regulation of apoptotic processCytochrome P450 1B1Homo sapiens (human)
blood vessel endothelial cell migrationCytochrome P450 1B1Homo sapiens (human)
endothelial cell migrationCytochrome P450 1B1Homo sapiens (human)
estrous cycleCytochrome P450 1B1Homo sapiens (human)
positive regulation of translationCytochrome P450 1B1Homo sapiens (human)
positive regulation of angiogenesisCytochrome P450 1B1Homo sapiens (human)
positive regulation of receptor signaling pathway via JAK-STATCytochrome P450 1B1Homo sapiens (human)
membrane lipid catabolic processCytochrome P450 1B1Homo sapiens (human)
response to arsenic-containing substanceCytochrome P450 1B1Homo sapiens (human)
blood vessel morphogenesisCytochrome P450 1B1Homo sapiens (human)
retinal blood vessel morphogenesisCytochrome P450 1B1Homo sapiens (human)
ganglion developmentCytochrome P450 1B1Homo sapiens (human)
cellular response to hydrogen peroxideCytochrome P450 1B1Homo sapiens (human)
cellular response to cAMPCytochrome P450 1B1Homo sapiens (human)
cellular response to tumor necrosis factorCytochrome P450 1B1Homo sapiens (human)
cellular response to luteinizing hormone stimulusCytochrome P450 1B1Homo sapiens (human)
cellular response to cortisol stimulusCytochrome P450 1B1Homo sapiens (human)
cellular response to progesterone stimulusCytochrome P450 1B1Homo sapiens (human)
response to dexamethasoneCytochrome P450 1B1Homo sapiens (human)
endothelial cell-cell adhesionCytochrome P450 1B1Homo sapiens (human)
response to indole-3-methanolCytochrome P450 1B1Homo sapiens (human)
cellular response to toxic substanceCytochrome P450 1B1Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 1B1Homo sapiens (human)
response to 3-methylcholanthreneCytochrome P450 1B1Homo sapiens (human)
regulation of reactive oxygen species metabolic processCytochrome P450 1B1Homo sapiens (human)
positive regulation of reactive oxygen species metabolic processCytochrome P450 1B1Homo sapiens (human)
positive regulation of DNA biosynthetic processCytochrome P450 1B1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (22)

Processvia Protein(s)Taxonomy
monooxygenase activityCytochrome P450 1A1Homo sapiens (human)
iron ion bindingCytochrome P450 1A1Homo sapiens (human)
protein bindingCytochrome P450 1A1Homo sapiens (human)
arachidonic acid monooxygenase activityCytochrome P450 1A1Homo sapiens (human)
oxidoreductase activityCytochrome P450 1A1Homo sapiens (human)
oxidoreductase activity, acting on diphenols and related substances as donorsCytochrome P450 1A1Homo sapiens (human)
flavonoid 3'-monooxygenase activityCytochrome P450 1A1Homo sapiens (human)
oxygen bindingCytochrome P450 1A1Homo sapiens (human)
enzyme bindingCytochrome P450 1A1Homo sapiens (human)
heme bindingCytochrome P450 1A1Homo sapiens (human)
Hsp70 protein bindingCytochrome P450 1A1Homo sapiens (human)
demethylase activityCytochrome P450 1A1Homo sapiens (human)
Hsp90 protein bindingCytochrome P450 1A1Homo sapiens (human)
aromatase activityCytochrome P450 1A1Homo sapiens (human)
vitamin D 24-hydroxylase activityCytochrome P450 1A1Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 1A1Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 1A1Homo sapiens (human)
long-chain fatty acid omega-hydroxylase activityCytochrome P450 1A1Homo sapiens (human)
hydroperoxy icosatetraenoate dehydratase activityCytochrome P450 1A1Homo sapiens (human)
long-chain fatty acid omega-1 hydroxylase activityCytochrome P450 1A1Homo sapiens (human)
monooxygenase activityCytochrome P450 1B1Homo sapiens (human)
iron ion bindingCytochrome P450 1B1Homo sapiens (human)
protein bindingCytochrome P450 1B1Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 1B1Homo sapiens (human)
heme bindingCytochrome P450 1B1Homo sapiens (human)
aromatase activityCytochrome P450 1B1Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 1B1Homo sapiens (human)
hydroperoxy icosatetraenoate dehydratase activityCytochrome P450 1B1Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygenCytochrome P450 1B1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (4)

Processvia Protein(s)Taxonomy
mitochondrial inner membraneCytochrome P450 1A1Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 1A1Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1A1Homo sapiens (human)
mitochondrionCytochrome P450 1B1Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 1B1Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1B1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (1)

Assay IDTitleYearJournalArticle
AID1453015Inhibition of recombinant CYP1B1 (unknown origin) expressed in Escherichia coli DH5alphaF'Iq coexpressing human NADPH-P450 reductase using E2-d4 as substrate after 10 mins in presence of NADP+2017European journal of medicinal chemistry, Jul-28, Volume: 135Inhibitors of cytochrome P450 (CYP) 1B1.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (21)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902 (9.52)18.7374
1990's4 (19.05)18.2507
2000's6 (28.57)29.6817
2010's9 (42.86)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 16.87

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 Index16.87 (24.57)
Research Supply Index3.09 (2.92)
Research Growth Index4.78 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (16.87)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (4.76%)6.00%
Case Studies0 (0.00%)4.05%
Observational1 (4.76%)0.25%
Other19 (90.48%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]