You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
FolliculinNot 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 KeyDNXHEGUUPJUMQT-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
Not Available
Estrone sulfateDetails
Estrone
Not Available
Estrone glucuronideDetails
Estrone
Not Available
2-Hydroxyestrone sulfateDetails
Estrone
Not Available
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 Solubility0.00394ALOGPS
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 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.08 m3·mol-1ChemAxon
Polarizability31.27 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
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

Targets

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

Enzymes

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

Carriers

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

Transporters

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11