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Identification
NameEstrone
Accession NumberDB00655  (APRD00588)
Typesmall molecule
Groupsapproved
Description

Estrone, 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
3-Hydroxy-1,3,5(10)-estratrien-17-oneNot AvailableNot Available
EstronaSpanishINN
EstroneNot AvailableINN, USAN
EstronumLatinINN
follicular hormoneNot AvailableNot Available
OestroneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
EstroneWatson
Brand mixtures
Brand NameIngredients
Cimicifuga PlexCaulophyllum Thalictroides + Cimicifuga Racemosa + Copper + Cotton Plant + Estrone + Histamine Dihydrochloride + Hypothalamus + Magnesium Phosphate Dibasic + Pituitary Whole + Platinum + Sepia Officinalis L + Thyroid
Categories
CAS number53-16-7
WeightAverage: 270.3661
Monoisotopic: 270.161979948
Chemical FormulaC18H22O2
InChI KeyInChIKey=DNXHEGUUPJUMQT-CBZIJGRNSA-N
InChI
InChI=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
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
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
Mass Specshow(9.95 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassKetosteroids
Direct parentKetosteroids
Alternative parentsHydroxysteroids; Phenanthrenes and Derivatives; Tetralins; Phenols and Derivatives; Ketones; Polyamines; Enols
Substituentsphenanthrene; tetralin; phenol derivative; benzene; ketone; polyamine; enol; carbonyl group
Classification descriptionThis compound belongs to the ketosteroids. These are steroid derivatives comprising a ketone group attached to steroid skeleton.
Pharmacology
IndicationFor management of perimenopausal and postmenopausal symptoms.
PharmacodynamicsEstrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency.
Mechanism of actionEstrogens 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.
Absorption43%
Volume of distributionNot Available
Protein binding> 95%
Metabolism

Hepatic.

SubstrateEnzymesProduct
Estrone
2-hydroxyestroneDetails
Estrone
4-hydroxyestroneDetails
Estrone
    Estrone sulfateDetails
    Estrone
      Estrone glucuronideDetails
      Estrone
        2-Hydroxyestrone sulfateDetails
        Estrone
          4-Hydroxyestrone sulfateDetails
          Route of eliminationNot Available
          Half life19 hours
          ClearanceNot Available
          ToxicitySymptoms 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.
          Affected organisms
          • Humans and other mammals
          PathwaysNot Available
          SNP Mediated EffectsNot Available
          SNP Mediated Adverse Drug ReactionsNot Available
          ADMET
          Predicted ADMET features
          Property Value Probability
          Human Intestinal Absorption + 1.0
          Blood Brain Barrier + 0.9529
          Caco-2 permeable + 0.8934
          P-glycoprotein substrate Substrate 0.6001
          P-glycoprotein inhibitor I Non-inhibitor 0.9066
          P-glycoprotein inhibitor II Non-inhibitor 0.8882
          Renal organic cation transporter Non-inhibitor 0.73
          CYP450 2C9 substrate Non-substrate 0.6624
          CYP450 2D6 substrate Non-substrate 0.9116
          CYP450 3A4 substrate Substrate 0.729
          CYP450 1A2 substrate Inhibitor 0.9017
          CYP450 2C9 substrate Non-inhibitor 0.9353
          CYP450 2D6 substrate Non-inhibitor 0.9599
          CYP450 2C19 substrate Non-inhibitor 0.8954
          CYP450 3A4 substrate Non-inhibitor 0.8309
          CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8681
          Ames test Non AMES toxic 0.9268
          Carcinogenicity Non-carcinogens 0.8917
          Biodegradation Not ready biodegradable 0.9717
          Rat acute toxicity 1.9267 LD50, mol/kg Not applicable
          hERG inhibition (predictor I) Weak inhibitor 0.8711
          hERG inhibition (predictor II) Inhibitor 0.5459
          Pharmacoeconomics
          Manufacturers
          • Wyeth ayerst laboratories
          • Watson laboratories inc
          • Parkedale pharmaceuticals inc
          Packagers
          Dosage forms
          FormRouteStrength
          CreamIntravaginal1 mg/g
          LiquidOral
          Solution / dropsOral
          Prices
          Unit descriptionCostUnit
          Estrone powder21.42USDg
          Estrone crystal11.76USDg
          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
          PatentsNot Available
          Properties
          Statesolid
          Experimental Properties
          PropertyValueSource
          melting point260.2 °CPhysProp
          boiling point154 °CPhysProp
          water solubility30 mg/L (at 25 °C)MERCK INDEX (1996)
          logP3.13HANSCH,C ET AL. (1995)
          logS-3.96ADME Research, USCD
          Predicted Properties
          PropertyValueSource
          water solubility3.94e-03 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 area37.3ChemAxon
          rotatable bond count0ChemAxon
          refractivity79.08ChemAxon
          polarizability31.27ChemAxon
          number of rings4ChemAxon
          bioavailability1ChemAxon
          rule of fiveYesChemAxon
          Ghose filterYesChemAxon
          Veber's ruleYesChemAxon
          MDDR-like ruleNoChemAxon
          Spectra
          Spectra
          References
          Synthesis Reference

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

          US5424462
          General Reference
          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. Pubmed
          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. Pubmed
          External Links
          ResourceLink
          KEGG DrugD00067
          KEGG CompoundC00468
          PubChem Compound5870
          PubChem Substance46505916
          ChemSpider5660
          BindingDB17289
          ChEBI17263
          ChEMBLCHEMBL1405
          Therapeutic Targets DatabaseDAP001020
          PharmGKBPA449512
          IUPHAR2818
          Guide to Pharmacology2818
          HETE3G
          Drug Product Database727369
          WikipediaEstrone
          ATC CodesG03CA07G03CC04
          AHFS Codes
          • 68:16.04
          • 92:02.00*
          PDB EntriesNot Available
          FDA labelNot Available
          MSDSshow(76.2 KB)
          Interactions
          Drug Interactions
          Drug
          FosphenytoinThe enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estrone.
          GriseofulvinThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estrone.
          PhenobarbitalThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estrone.
          PhenytoinThe enzyme inducer, phenytoin, decreases the effect of the hormone agent, estrone.
          PrednisoloneThe estrogenic agent, estrone, may increase the effect of the corticosteroid, prednisolone.
          PrednisoneThe estrogenic agent, estrone, may increase the effect of corticosteroid, prednisone.
          PrimidoneThe enzyme inducer, primidone, decreases the effect of the hormone agent, estrone.
          TipranavirEstropipate may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Estropipate. Monitor for estrogen deficiency during concomitant therapy.
          Food InteractionsNot Available

          1. Estrogen receptor

          Kind: protein

          Organism: Human

          Pharmacological action: yes

          Actions: agonist

          Components

          Name UniProt ID Details
          Estrogen receptor P03372 Details

          References:

          1. Margeat E, Bourdoncle A, Margueron R, Poujol N, Cavailles V, Royer C: Ligands differentially modulate the protein interactions of the human estrogen receptors alpha and beta. J Mol Biol. 2003 Feb 7;326(1):77-92. Pubmed
          2. Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. Pubmed
          3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

          1. Cytochrome P450 1A1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 1A1 P04798 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          2. Cytochrome P450 1A2

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 1A2 P05177 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
          2. Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M: Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):368-74. Pubmed

          3. Cytochrome P450 3A4

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 3A4 P08684 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
          2. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. Pubmed

          4. Cytochrome P450 1B1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 1B1 Q16678 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          5. Cytochrome P450 2B6

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 2B6 P20813 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          6. Cytochrome P450 2C9

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 2C9 P11712 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          7. Cytochrome P450 2E1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 2E1 P05181 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          8. Cytochrome P450 3A5

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 3A5 P20815 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          9. Cytochrome P450 4A11

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Cytochrome P450 4A11 Q02928 Details

          References:

          1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          1. Serum albumin

          Kind: protein

          Organism: Human

          Pharmacological action: no

          Components

          Name UniProt ID Details
          Serum albumin P02768 Details

          References:

          1. Tan E, Lu T, Pang KS: Futile cycling of estrone sulfate and estrone in the recirculating perfused rat liver preparation. J Pharmacol Exp Ther. 2001 Apr;297(1):423-36. Pubmed

          1. Solute carrier organic anion transporter family member 2B1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Solute carrier organic anion transporter family member 2B1 O94956 Details

          References:

          1. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. Pubmed

          2. Multidrug resistance protein 1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate inducer

          Components

          Name UniProt ID Details
          Multidrug resistance protein 1 P08183 Details

          References:

          1. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. Epub 2009 May 12. Pubmed
          2. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. Pubmed

          3. Solute carrier organic anion transporter family member 1A2

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Solute carrier organic anion transporter family member 1A2 P46721 Details

          References:

          1. Kanai N, Lu R, Bao Y, Wolkoff AW, Vore M, Schuster VL: Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. Am J Physiol. 1996 Feb;270(2 Pt 2):F326-31. Pubmed

          4. ATP-binding cassette sub-family G member 2

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: inhibitor

          Components

          Name UniProt ID Details
          ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

          References:

          1. Imai Y, Tsukahara S, Asada S, Sugimoto Y: Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res. 2004 Jun 15;64(12):4346-52. Pubmed
          2. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. Pubmed
          3. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. Pubmed
          4. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 2003 Sep;64(3):610-8. Pubmed
          5. Miwa M, Tsukahara S, Ishikawa E, Asada S, Imai Y, Sugimoto Y: Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants. Int J Cancer. 2003 Dec 10;107(5):757-63. Pubmed
          6. Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Estrone and 17beta-estradiol reverse breast cancer resistance protein-mediated multidrug resistance. Jpn J Cancer Res. 2002 Mar;93(3):231-5. Pubmed

          5. Solute carrier organic anion transporter family member 1B1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

          References:

          1. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. Pubmed

          Comments
          Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11