Identification

Name
Dienestrol
Accession Number
DB00890  (APRD00917)
Type
Small Molecule
Groups
Approved, Investigational
Description

Dienestrol is a synthetic, non-steroidal estrogen. It is an estrogen receptor agonist. Estrogens work partly by increasing a normal clear discharge from the vagina and making the vulva and urethra healthy. Using or applying an estrogen relieves or lessens: dryness and soreness in the vagina, itching, redness, or soreness of the vulva. Conditions that are treated with vaginal estrogens include a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis), and inflammation of the urethra (atrophic urethritis).

Structure
Thumb
Synonyms
  • alpha-dienestrol diacetate
  • Cycladiene
  • Dehydrostilbestrol
  • Dienestrol
  • Diènestrol
  • Dienestrolum
  • DV
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ortho Dienestrol CrmCream.01 %VaginalOrtho Pharmaceutical, Division Of Janssen Ortho Inc.1951-12-312002-08-02Canada
International/Other Brands
Estraguard / Estraguard / Estroral / Ortho Dienestrol (Ortho-McNeil Pharmaceutical) / Restrol / Retalon / Sexadien (LEO Pharma A/S) / Synestrol
Categories
UNII
RRW32X4U1F
CAS number
13029-44-2
Weight
Average: 266.3343
Monoisotopic: 266.13067982
Chemical Formula
C18H18O2
InChI Key
NFDFQCUYFHCNBW-SCGPFSFSSA-N
InChI
InChI=1S/C18H18O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h3-12,19-20H,1-2H3/b17-3+,18-4+
IUPAC Name
4-[4-(4-hydroxyphenyl)hexa-2,4-dien-3-yl]phenol
SMILES
CC=C(C(=CC)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1

Pharmacology

Indication

For use in the treatment of atrophic vaginitis and kraurosis vulvae.

Pharmacodynamics

Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

Mechanism of action

Dienestrol is a synthetic, non-steroidal estrogen. Estrogens passively diffuse into target cells of responsive tissues, complex with the estrogen receptors, and enter the cell's nucleus to initiate or enhance gene transcription of protein synthesis after binding to DNA.

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Human
USex hormone-binding globulinNot AvailableHuman
Absorption

Systemic absorption and mode of action of dienestrol are undetermined.Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

Volume of distribution
Not Available
Protein binding

50 to 80%

Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe serum concentration of 16-Bromoepiandrosterone can be increased when it is combined with Dienestrol.
19-norandrostenedioneThe serum concentration of 19-norandrostenedione can be increased when it is combined with Dienestrol.
5-androstenedioneThe serum concentration of 5-androstenedione can be increased when it is combined with Dienestrol.
AbciximabDienestrol may decrease the anticoagulant activities of Abciximab.
AceclofenacAceclofenac may increase the thrombogenic activities of Dienestrol.
AcenocoumarolDienestrol may decrease the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidDienestrol may decrease the anticoagulant activities of Acetylsalicylic acid.
AldosteroneThe serum concentration of Aldosterone can be increased when it is combined with Dienestrol.
AlemtuzumabDienestrol may increase the thrombogenic activities of Alemtuzumab.
AlteplaseDienestrol may decrease the anticoagulant activities of Alteplase.
Food Interactions
Not Available

References

Synthesis Reference

Short, W.F. and Hobday, G.1; U.S. Patent 2,464,203; March 15,1949; assigned to Boots Pure Drug Company Limited, England. Adler, E.; U.S. Patent 2,465,505; March 29,1949; assigned to Hoffmann-La Roche Inc.

General References
Not Available
External Links
KEGG Drug
D00898
KEGG Compound
C08090
PubChem Compound
667476
PubChem Substance
46504661
ChemSpider
580857
BindingDB
40491
ChEBI
4518
ChEMBL
CHEMBL1018
Therapeutic Targets Database
DAP001015
PharmGKB
PA164745534
RxList
RxList Drug Page
Wikipedia
Dienestrol
ATC Codes
G03CB01 — DienestrolG03CC02 — Dienestrol
MSDS
Download (75.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentBipolar Disorder (BD) / Mania1

Pharmacoeconomics

Manufacturers
  • Ortho mcneil pharmaceutical inc
  • Sanofi aventis us llc
  • Solvay pharmaceuticals
Packagers
  • Spectrum Pharmaceuticals
Dosage forms
FormRouteStrength
CreamVaginal.01 %
Prices
Unit descriptionCostUnit
Dienestrol powder442.23USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)233-234Short, W.F. and Hobday, G.1; U.S. Patent 2,464,203; March 15,1949; assigned to Boots Pure Drug Company Limited, England.
water solubility3 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP5.9Not Available
logS-4.95ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0123 mg/mLALOGPS
logP5.18ALOGPS
logP4.83ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.1ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity84.36 m3·mol-1ChemAxon
Polarizability30.3 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9971
Blood Brain Barrier-0.7087
Caco-2 permeable+0.8916
P-glycoprotein substrateNon-substrate0.5491
P-glycoprotein inhibitor INon-inhibitor0.7795
P-glycoprotein inhibitor IINon-inhibitor0.9557
Renal organic cation transporterNon-inhibitor0.8322
CYP450 2C9 substrateNon-substrate0.7849
CYP450 2D6 substrateNon-substrate0.8857
CYP450 3A4 substrateNon-substrate0.544
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8605
CYP450 2D6 inhibitorNon-inhibitor0.8201
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8844
Ames testNon AMES toxic0.9658
CarcinogenicityNon-carcinogens0.7133
BiodegradationNot ready biodegradable0.7876
Rat acute toxicity1.8229 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7994
hERG inhibition (predictor II)Non-inhibitor0.8584
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.48 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Styrenes / 1-hydroxy-2-unsubstituted benzenoids / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Stilbene / Styrene / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Benzenoid / Monocyclic benzene moiety / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Aromatic homomonocyclic compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, olefinic compound (CHEBI:4518)

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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Juriansz RL, Huseby RA, Wilcox RB: Interactions of putative estrogens with the intracellular receptor complex in mouse Leydig cells: relationship to preneoplastic hyperplasia. Cancer Res. 1988 Jan 1;48(1):14-8. [PubMed:3334987]
  2. Grove RI, Korach KS: Estrogen stimulation of phosphatidylinositol metabolism in mouse uterine tissue. Endocrinology. 1987 Sep;121(3):1083-8. [PubMed:3622377]
  3. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997 Mar;138(3):863-70. [PubMed:9048584]
  4. Chae K, Lindzey J, McLachlan JA, Korach KS: Estrogen-dependent gene regulation by an oxidative metabolite of diethylstilbestrol, diethylstilbestrol-4',4"-quinone. Steroids. 1998 Mar;63(3):149-57. [PubMed:9558716]
  5. Bovee TF, Helsdingen RJ, Rietjens IM, Keijer J, Hoogenboom RL: Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types. J Steroid Biochem Mol Biol. 2004 Jul;91(3):99-109. [PubMed:15276617]
  6. Maru BS, Tobias JH, Rivers C, Caunt CJ, Norman MR, McArdle CA: Potential use of an estrogen-glucocorticoid receptor chimera as a drug screen for tissue selective estrogenic activity. Bone. 2009 Jan;44(1):102-12. doi: 10.1016/j.bone.2008.09.016. Epub 2008 Oct 11. [PubMed:18976723]
  7. 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
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 12:55