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targets (2) transporters (2)
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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. 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(16α,17β)-estra-1,3,5(10)-triene-3,16,17-triol
16-alpha-Hydroxyestradiol
16alpha-hydroxyestradiol
16α-hydroxyestradiol
Oestriol
Salts
  • Estriol tripropionate
Brand names
Name Company
Trimesta
Brand 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 (2.96 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 Not Available
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
Form Route Strength
Cream Intravaginal 0.5mg
Cream Intravaginal 1.0mg
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 282 °C PhysProp
logP 2.45 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.19e-01 g/l ALOGPS
logP 2.54 ALOGPS
logP 2.67 ChemAxon
logS -3.4 ALOGPS
pKa (strongest acidic) 10.33 ChemAxon
pKa (strongest basic) -3.2 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 60.69 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 81.27 ChemAxon
polarizability 33.07 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00185 Link_out
KEGG Compound C05141 Link_out
PubChem Compound 5756 Link_out
PubChem Substance 46505881 Link_out
ChemSpider 5553 Link_out
ChEBI 27974 Link_out
ChEMBL 27974 Link_out
Therapeutic Targets Database DAP001019 Link_out
PharmGKB PA164769104 Link_out
HET ESL Link_out
Wikipedia http://en.wikipedia.org/wiki/Estriol Link_out
ATC Codes
  • G03CC06
  • G03CA04
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (75.9 KB)
Interactions
Drug Interactions
Drug Interaction
Fosphenytoin The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estriol.
Griseofulvin The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estriol.
Phenobarbital The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estriol.
Phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estriol.
Prednisolone The estrogenic agent, estriol, may increase the effect of the corticosteroid, prednisolone.
Prednisone The estrogenic agent, estriol, may increase the effect of corticosteroid, prednisone.
Primidone The enzyme inducer, primidone, decreases the effect of the hormone agent, estriol.
Raloxifene Association not recommended
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 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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:
  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

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:
  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

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:
  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 February 08, 2013 16:23