DrugBank: Estriol (DB04573)

targets (2) transporters (2)

Identification

Name

Estriol

Accession Number

DB04573 (DB05375, EXPT01361)

Type

small molecule

Groups

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.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

(16alpha,17beta)-estra-1,3,5(10)-triene-3,16,17-triol
(16alpha,17beta)-Oestra-1,3,5(10)-triene-3,16,17-triol
1,3,5-Estratriene-3beta,16alpha,17beta-triol
1,3,5-Oestratriene-3beta,16alpha,17beta-triol
1,3,5(10)-Estratriene-3,16,17-Triol
1,3,5(10)-Estratriene-3,16alpha,17beta-triol
16-alpha-Hydroxyestradiol
16-alpha-Hydroxyoestradiol
16-alpha,17-beta-Estriol
16-alpha,17-beta-Oestriol
16alpha-Hydroxy-17beta-estradiol
16alpha-hydroxyestradiol
16alpha-Hydroxyoestradiol
16alpha,17beta-Estriol
16alpha,17beta-Oestriol
3,16-alpha,17-beta-Estriol
3,16-alpha,17-beta-Oestriol
3,16-alpha,17-beta-Trihydroxy-delta-1,3,5-estratriene
3,16-alpha,17-beta-Trihydroxy-delta-1,3,5-oestratriene
3,16-alpha,17-beta-Trihydroxyestra-1,3,5(10)-triene
3,16-alpha,17-beta-Trihydroxyoestra-1,3,5(10)-triene
3,16alpha,17beta-Estriol
3,16alpha,17beta-Trihydroxy-1,3,5(10)-estratriene
3,16alpha,17beta-Trihydroxy-delta-1,3,5-oestratriene
3,16alpha,17beta-trihydroxy-Delta(1,3,5)-estratriene
ESL
Estra-1,3,5(10)-trien-3,16alpha,17beta-triol
Estra-1,3,5(10)-triene-3,16,17-triol
Estratriol
Estriolo [italian]
Oestra-1,3,5(10)-triene-3,16alpha,17beta-triol
Oestriol
Oestriolum
Ovestrion
Tridestrin

Brand names

Deuslon-A
Estriel

Brand name mixtures

Not Available

Categories

Estrogens

CAS number

50-27-1

Weight

Average: 288.3814
Monoisotopic: 288.172544634

Chemical Formula

C₁₈H₂₄O₃

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

show (3 KB)

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Hydroxy Compounds
Naphthalenes
Phenols and Derivatives
Benzene and Derivatives
Phenanthrenes
Alcohols and Polyols
Aromatic compounds
Cyclohexenes and Derivatives
Phenyl Esters

Pharmacology

Indication

Used as a test to determine the general health of an unborn fetus.

Pharmacodynamics

Estriol (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 action

Estriol 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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

ORAL (LD50): Acute: >2000 mg/kg [Rat].

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

282 oC

Experimental Properties

Property	Value	Source
logP	2.45 [HANSCH,C ET AL. (1995)]	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.19e-01 g/l	ALOGPS
logP	2.54	ALOGPS
logP	2.67	ChemAxon Molconvert
logS	-3.38	ALOGPS
pKa	13.62	ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	60.69	ChemAxon Molconvert
rotatable bond count	0	ChemAxon Molconvert
refractivity	81.27	ChemAxon Molconvert
polarizability	33.07	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

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

External Links

Resource	Link
KEGG Drug	D00185
KEGG Compound	C05141
PubChem Compound	5756
PubChem Substance	46505881
ChemSpider	5553
ChEBI	27974
ChEMBL	27974
Therapeutic Targets Database	DAP001019
HET	ESL
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Estriol

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (75.9 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Estrogen receptor Pharmacological action: yes Actions: agonist 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 Organism class: human UniProt ID: P03372 Gene: ESR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 Pharmacological action: unknown Actions: agonist 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. 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 ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual Organism class: human UniProt ID: Q92731 Gene: ESR2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Targets

1. Estrogen receptor

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P03372 Link_out

Gene: ESR1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Pharmacological action: unknown
Actions: agonist

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. 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 ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual

Organism class: human
UniProt ID: Q92731 Link_out

Gene: ESR2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 Actions: inhibitor Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity) UniProt ID: P46721 Gene: SLCO1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: substrate, inducer Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Transporters

1. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out

Gene: SLCO1A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: substrate, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 October 11, 2011 16:49

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.