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Record Information
Version2.0
Creation Date2014-09-11 05:14:33 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4746
Identification
Common NameEstrone
ClassSmall Molecule
DescriptionEstrone, one of the major mammalian estrogens, is an aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone. It is produced in vivo from androstenedione or from testosterone via estradiol. It is produced primarily in the ovaries, placenta, and in peripheral tissues (especially adipose tissue) through conversion of adrostenedione. Estrone may be further metabolized to 16-alpha-hydroxyestrone, which may be reduced to estriol by estradiol dehydrogenase.
Compound Type
  • Animal Toxin
  • Anti-Menopausal Agent
  • Drug
  • Estrogen
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Estrone
1,3,5(10)-Estratrien-3-ol-17-one
3-Hydroxy-1,3,5(10)-estratrien-17-one
3-Hydroxy-17-keto-estra-1,3,5-triene
3-Hydroxyestra-1,3,5(10)-trien-17-one
3-Hydroxyestra-1,3,5(10)-triene-17-one
3-Hydroxyoestra-1,3,5(10)-trien-17-one
D1,3,5(10)-Estratrien-3-ol-17-one
Estrona
Estronum
follicular hormone
Folliculin
Oestrone
Chemical FormulaC18H22O2
Average Molecular Mass270.366 g/mol
Monoisotopic Mass270.162 g/mol
CAS Registry Number53-16-7
IUPAC Name(1S,10R,11S,15S)-5-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-one
Traditional Name(1S,10R,11S,15S)-5-hydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-one
SMILES[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3CC[C@@]21[H]
InChI IdentifierInChI=1S/C18H22O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-16,19H,2,4,6-9H2,1H3/t14-,15-,16+,18+/m1/s1
InChI KeyInChIKey=DNXHEGUUPJUMQT-CBZIJGRNSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 3-hydroxysteroid
  • Hydroxysteroid
  • 17-oxosteroid
  • Oxosteroid
  • Phenanthrene
  • Tetralin
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Ketone
  • Carbonyl group
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Androgen and Estrogen MetabolismSMP00068 map00150
Sulfate/Sulfite MetabolismSMP00041 map00920
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point260.2°C
Boiling Point154°C
Solubility30 mg/L (at 25°C)
LogP3.13
Predicted Properties
PropertyValueSource
Water Solubility0.0039 g/LALOGPS
logP4.03ALOGPS
logP4.31ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.08 m³·mol⁻¹ChemAxon
Polarizability31.24 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-05ox-3951000000-8bc438f505b3cf49b21fJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-003u-4942000000-a72ea34d85d9d524c247JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-0019-8931000000-aad9803af812c7c40f53JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-2940000000-2d417e7ecb4a8b87b817JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-0980000000-5b293db89a0f2efeb784JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-05ox-3951000000-8bc438f505b3cf49b21fJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-003u-4942000000-a72ea34d85d9d524c247JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0019-8931000000-aad9803af812c7c40f53JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0adl-1970000000-871531490fb22b8fe12fJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-009t-1093000000-a8d755d13e3b819514c8JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-0190000000-071e67516e11357ff64eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4j-4910000000-20e059a7c508ba492af3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-067i-9700000000-9ff5214f08822f238fa9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-00di-2940000000-3b9744c27d6a3d2eff6eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0ukc-2690000000-7afb48e267c7b334213bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0690000000-a76244de959b06ec896eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a59-0910000000-4a1bc1cbc90c3e5281e6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a59-0900000000-0830d4ad43804976f508JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0390000000-41440e74b3f0b5f365d7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0390000000-fdc0255246e3a9013d0aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a59-2910000000-fc5173d435c3c7fc603cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00di-0390000000-25cecb1c4785e7bffd56JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0190000000-64cf013a5b0ad5e8bf56JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00fr-0590000000-40418c285df2157226dcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fb9-6980000000-724c68b368fbe3d38f5eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-6778bd7122813b501c1eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0090000000-0f2e0b96bc30b346c581JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f9i-1090000000-9ccbd9f351dd1f8e52cbJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-00di-2930000000-c99df908474247066a2bJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of Exposure43%
Mechanism of ToxicityEstrogens enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) release from the anterior pituitary.
MetabolismHepatic. Half Life: 19 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor management of perimenopausal and postmenopausal symptoms.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include nausea and vomiting. Estrogen related side effects include nausea, breast tenderness, fluid retention and edema, headaches and/or migraines, chloasma and poor contact lens fit. Estrogen hormone deficiency is associated with breakthrough bleeding, hypomenorrhea, irritability, depression and menopausal symptoms. Withdrawal bleeds may occur in females.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00655
HMDB IDHMDB00145
PubChem Compound ID5870
ChEMBL IDCHEMBL1405
ChemSpider ID5660
KEGG IDC00468
UniProt IDNot Available
OMIM ID
ChEBI ID17263
BioCyc IDESTRONE
CTD IDNot Available
Stitch IDNot Available
PDB IDJ3Z
ACToR IDNot Available
Wikipedia LinkEstrone
References
Synthesis Reference

Seiichi Takano, Kunio Ogasawara, “Method for producing (+)-estrone derivatives.” U.S. Patent US5424462, issued January, 1965.

MSDSLink
General References
  1. Miyoshi Y, Tanji Y, Taguchi T, Tamaki Y, Noguchi S: Association of serum estrone levels with estrogen receptor-positive breast cancer risk in postmenopausal Japanese women. Clin Cancer Res. 2003 Jun;9(6):2229-33. [12796390 ]
  2. Kajta M, Lason W, Bien E, Marszal M: Neuroprotective effects of estrone on NMDA-induced toxicity in primary cultures of rat cortical neurons are independent of estrogen receptors. Pol J Pharmacol. 2002 Nov-Dec;54(6):727-9. [12866733 ]
  3. Czernik PJ, Little JM, Barone GW, Raufman JP, Radominska-Pandya A: Glucuronidation of estrogens and retinoic acid and expression of UDP-glucuronosyltransferase 2B7 in human intestinal mucosa. Drug Metab Dispos. 2000 Oct;28(10):1210-6. [10997942 ]
  4. Pfeiffer E, Graf E, Gerstner S, Metzler M: Stimulation of estradiol glucuronidation: a protective mechanism against estradiol-mediated carcinogenesis? Mol Nutr Food Res. 2006 Apr;50(4-5):385-9. [16598814 ]
  5. Kuhl H, Wiegratz I: Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications? Climacteric. 2007 Aug;10(4):344-53. [17653961 ]
  6. Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS: Ovarian conservation at the time of hysterectomy for benign disease. Clin Obstet Gynecol. 2007 Jun;50(2):354-61. [17513923 ]
  7. Stanway SJ, Delavault P, Purohit A, Woo LW, Thurieau C, Potter BV, Reed MJ: Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist. 2007 Apr;12(4):370-4. [17470679 ]
  8. Ito K: Hormone replacement therapy and cancers: the biological roles of estrogen and progestin in tumorigenesis are different between the endometrium and breast. Tohoku J Exp Med. 2007 May;212(1):1-12. [17464097 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0061 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.0303 uMATG_ERa_TRANSAttagene
AC500.091 uMATG_ERE_CISAttagene
AC500.000795 uMNVS_NR_hERNovascreen
AC500.315 uMOT_ER_ERaERa_0480Odyssey Thera
AC500.661 uMOT_ER_ERaERa_1440Odyssey Thera
AC500.00145 uMOT_ERa_EREGFP_0120Odyssey Thera
AC500.00146 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.000878 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.000458 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0601 uMNVS_NR_hARNovascreen
AC501.21 uMTox21_AR_LUC_MDAKB2_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0881 uMOT_ER_ERaERb_0480Odyssey Thera
AC500.879 uMOT_ER_ERaERb_1440Odyssey Thera
AC500.0916 uMOT_ER_ERbERb_0480Odyssey Thera
AC500.424 uMOT_ER_ERbERb_1440Odyssey Thera
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.105 uMNVS_NR_hPRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.67 uMATG_PXR_TRANSAttagene
AC507.71 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]