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Identification
NameEstriol
Accession NumberDB04573  (EXPT01361, DB05375)
TypeSmall Molecule
GroupsApproved, Vet Approved
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
(16alpha,17beta)-Estra-1,3,5(10)-triene-3,16,17-triol
(16α,17β)-estra-1,3,5(10)-triene-3,16,17-triol
1,3,5(10)-Estratriene-3,16-alpha,17beta-triol
16-alpha-Hydroxyestradiol
16alpha-hydroxyestradiol
16α-hydroxyestradiol
3,16alpha,17beta-Trihydroxy-delta(1,3,5)-estratriene
Deuslon-a
Estriel
Estriol
Oestriol
Trihydroxyestrin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AacifemineOrganon
ColpoestriolTemis-Lostalo
OvestinMerck Sharp & Dohme
Synapause EOrganon
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Estriol tripropionate
Thumb
  • InChI Key: ONMZMZJEZHMWQL-REUUDLSRSA-N
  • Monoisotopic Mass: 456.251188884
  • Average Mass: 456.5711
DBSALT000069
Categories
UNIIFB33469R8E
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[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-triene-5,13,14-triol
SMILES
[H][C@@]12C[C@@H](O)[[email protected]](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
Taxonomy
DescriptionThis compound 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
  • 17-hydroxysteroid
  • 16-hydroxysteroid
  • 16-alpha-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • Benzenoid
  • Cyclic alcohol
  • Secondary alcohol
  • Polyol
  • 1,2-diol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.7057
Caco-2 permeable+0.7591
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor INon-inhibitor0.9208
P-glycoprotein inhibitor IINon-inhibitor0.9805
Renal organic cation transporterNon-inhibitor0.8619
CYP450 2C9 substrateNon-substrate0.7536
CYP450 2D6 substrateNon-substrate0.7993
CYP450 3A4 substrateSubstrate0.6892
CYP450 1A2 substrateNon-inhibitor0.6618
CYP450 2C9 inhibitorNon-inhibitor0.9399
CYP450 2D6 inhibitorNon-inhibitor0.9619
CYP450 2C19 inhibitorNon-inhibitor0.7086
CYP450 3A4 inhibitorNon-inhibitor0.8932
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9152
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9147
BiodegradationNot ready biodegradable0.9811
Rat acute toxicity1.9758 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.948
hERG inhibition (predictor II)Inhibitor0.7684
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
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 Solubility0.119 mg/mLALOGPS
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 Area60.69 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity81.27 m3·mol-1ChemAxon
Polarizability33.07 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (2.96 KB)
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-005a-1983000000-2f46d0d29b48132f7670View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-5900000000-2102cb581ac98fea87b0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-1900000000-1fab12be883127f80c67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-5900000000-2102cb581ac98fea87b0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-01-SG-2) , Positivesplash10-000i-4970000000-1aa2bbf3f32fd687c37dView in MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-3950000000-c2f0781bc5056d66aaf5View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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 References
  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:14634144 ]
  2. Trimesta [Link]
External Links
ATC CodesG03CA04G03CC06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (75.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 fact...
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
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:2011412 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
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...
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
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:16199482 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibited by the grapefruit juice component naringin.
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular Weight:
74144.105 Da
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:8779894 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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:15290871 ]
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Drug created on September 07, 2007 15:04 / Updated on September 16, 2013 17:25