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Identification
NameEstriol
Accession NumberDB04573  (DB05375, EXPT01361)
Typesmall molecule
Groupsapproved
Description

A hydroxylated metabolite of estradiol or estrone that has a hydroxyl group at C3-beta, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Though estriol is used as part of the primarily North American phenomenon of bioidentical hormone replacement therapy, it is not approved for use by the FDA or Health Canada. It is however available in the United States by prescription filled only by compounding pharmacies. It has also been approved and marketed throughout Europe and Asia for approximately 40 years for the treatment of post-menopausal hot flashes.

Structure
Thumb
Synonyms
SynonymLanguageCode
(16alpha,17beta)-Estra-1,3,5(10)-triene-3,16,17-triolNot AvailableNot Available
(16α,17β)-estra-1,3,5(10)-triene-3,16,17-triolNot AvailableNot Available
1,3,5(10)-Estratriene-3,16-alpha,17beta-triolNot AvailableNot Available
16-alpha-HydroxyestradiolNot AvailableNot Available
16alpha-hydroxyestradiolNot AvailableNot Available
16α-hydroxyestradiolNot AvailableNot Available
3,16alpha,17beta-Trihydroxy-delta(1,3,5)-estratrieneNot AvailableNot Available
Deuslon-aNot AvailableNot Available
EstrielNot AvailableNot Available
EstriolNot AvailableNot Available
OestriolNot AvailableNot Available
TrihydroxyestrinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Estriol tripropionate
Thumb
  • InChI Key: ONMZMZJEZHMWQL-REUUDLSRSA-N
  • Monoisotopic Mass: 456.251188884
  • Average Mass: 456.5711
DBSALT000069
Brand names
NameCompany
AacifemineOrganon
ColpoestriolTemis-Lostalo
OvestinMerck Sharp & Dohme
Synapause EOrganon
Brand mixturesNot Available
CategoriesNot Available
CAS number50-27-1
WeightAverage: 288.3814
Monoisotopic: 288.172544634
Chemical FormulaC18H24O3
InChI KeyPROQIPRRNZUXQM-ZXXIGWHRSA-N
InChI
InChI=1S/C18H24O3/c1-18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-17,19-21H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,17+,18+/m1/s1
IUPAC Name
(1S,10R,11S,13R,14R,15S)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,13,14-triol
SMILES
[H][C@@]12C[C@@H](O)[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
Mass Specshow(2.96 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassHydroxysteroids
Direct parentHydroxysteroids
Alternative parentsPhenanthrenes and Derivatives; Tetralins; Phenols and Derivatives; 1,2-Diols; Secondary Alcohols; Cyclic Alcohols and Derivatives; Enols; Polyamines
Substituentsphenanthrene; tetralin; phenol derivative; benzene; cyclic alcohol; secondary alcohol; 1,2-diol; polyol; polyamine; enol; alcohol
Classification descriptionThis compound belongs to the hydroxysteroids. These are compounds containing an steroid backbone, with at least one hydrogen substituted by an hydroxyl group.
Pharmacology
IndicationUsed as a test to determine the general health of an unborn fetus.
PharmacodynamicsEstriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.
Mechanism of actionEstriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estriol upon the target cell. 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) from the anterior pituitary.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Estriol
Not Available
Estriol-16-GlucuronideDetails
Estriol
Not Available
Estriol-17-glucuronideDetails
Estriol
Not Available
Estriol-3-glucuronideDetails
Estriol
Not Available
16-alpha,17-beta-estriol 17-beta-D-glucuronideDetails
Estriol
Not Available
Estriol 3-sulfate 16-glucuronideDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityORAL (LD50): Acute: >2000 mg/kg [Rat].
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 + 0.9966
Blood Brain Barrier + 0.7057
Caco-2 permeable + 0.7591
P-glycoprotein substrate Substrate 0.7862
P-glycoprotein inhibitor I Non-inhibitor 0.9208
P-glycoprotein inhibitor II Non-inhibitor 0.9805
Renal organic cation transporter Non-inhibitor 0.8619
CYP450 2C9 substrate Non-substrate 0.7536
CYP450 2D6 substrate Non-substrate 0.7993
CYP450 3A4 substrate Substrate 0.6892
CYP450 1A2 substrate Non-inhibitor 0.6618
CYP450 2C9 substrate Non-inhibitor 0.9399
CYP450 2D6 substrate Non-inhibitor 0.9619
CYP450 2C19 substrate Non-inhibitor 0.7086
CYP450 3A4 substrate Non-inhibitor 0.8932
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9152
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.9147
Biodegradation Not ready biodegradable 0.9811
Rat acute toxicity 1.9758 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.948
hERG inhibition (predictor II) Inhibitor 0.7684
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
CreamIntravaginal0.5mg
CreamIntravaginal1.0mg
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point82-86Organon Laboratories Limited, England; British Patent 879,014; October 4, 1961.
logP2.45HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility1.19e-01 g/lALOGPS
logP2.54ALOGPS
logP2.67ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)10.33ChemAxon
pKa (strongest basic)-3.2ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count3ChemAxon
polar surface area60.69ChemAxon
rotatable bond count0ChemAxon
refractivity81.27ChemAxon
polarizability33.07ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
References
Synthesis Reference

James V. Freeman, Gary M. Johnson, “Synthesis of 6.alpha.-functionalized estriol haptens and protein conjugates thereof.” U.S. Patent US5902888, issued June, 1973.

US5902888
General Reference
  1. Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR: Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol. 2003 Dec 1;171(11):6267-74. Pubmed
  2. Trimesta
External Links
ResourceLink
KEGG DrugD00185
KEGG CompoundC05141
PubChem Compound5756
PubChem Substance46505881
ChemSpider5553
ChEBI27974
ChEMBLCHEMBL193482
Therapeutic Targets DatabaseDAP001019
PharmGKBPA164769104
HETESL
WikipediaEstriol
ATC CodesG03CC06G03CA04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(75.9 KB)
Interactions
Drug Interactions
Drug
FosphenytoinThe enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estriol.
GriseofulvinThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estriol.
PhenobarbitalThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estriol.
PhenytoinThe enzyme inducer, phenytoin, decreases the effect of the hormone agent, estriol.
PrednisoloneThe estrogenic agent, estriol, may increase the effect of the corticosteroid, prednisolone.
PrednisoneThe estrogenic agent, estriol, may increase the effect of corticosteroid, prednisone.
PrimidoneThe enzyme inducer, primidone, decreases the effect of the hormone agent, estriol.
RaloxifeneAssociation not recommended
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. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen receptor beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Estrogen receptor beta Q92731 Details

References:

  1. Mishra RG, Stanczyk FZ, Burry KA, Oparil S, Katzenellenbogen BS, Nealen ML, Katzenellenbogen JA, Hermsmeyer RK: Metabolite ligands of estrogen receptor-beta reduce primate coronary hyperreactivity. Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H295-303. Epub 2005 Sep 30. Pubmed

Transporters

1. 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

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. 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

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Drug created on September 07, 2007 15:04 / Updated on September 16, 2013 17:25