Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
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
(16α,17β)-estra-1,3,5(10)-triene-3,16,17-triolNot AvailableNot Available
16-alpha-HydroxyestradiolNot AvailableNot Available
16alpha-hydroxyestradiolNot AvailableNot Available
16α-hydroxyestradiolNot AvailableNot Available
OestriolNot 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
TrimestaNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number50-27-1
WeightAverage: 288.3814
Monoisotopic: 288.172544634
Chemical FormulaC18H24O3
InChI KeyInChIKey=PROQIPRRNZUXQM-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
    Estriol-16-GlucuronideDetails
    Estriol
      Estriol-17-glucuronideDetails
      Estriol
        Estriol-3-glucuronideDetails
        Estriol
          16-alpha,17-beta-estriol 17-beta-D-glucuronideDetails
          Estriol
            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 point282 °CPhysProp
            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
            Spectra
            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

            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

            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

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