Dienestrol

Identification

Summary

Dienestrol is a non steroidal estrogen used to treat atrophic vaginitis and kraurosis vulvae.

Generic Name
Dienestrol
DrugBank Accession Number
DB00890
Background

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).

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 266.34
Monoisotopic: 266.13067982
Chemical Formula
C18H18O2
Synonyms
  • 4,4'-Hydroxy-γ,δ-diphenyl-β,δ-hexadiene
  • alpha-dienestrol diacetate
  • Cycladiene
  • Dehydrostilbestrol
  • Dienestrol
  • Diènestrol
  • Dienestrolum
  • p,p'-(Diethylideneethylene)diphenol

Pharmacology

Indication

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

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Contraindications & Blackbox Warnings
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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
Humans
USex hormone-binding globulinNot AvailableHumans
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

Adverse Effects
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Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabDienestrol may increase the thrombogenic activities of Abciximab.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dienestrol.
AdalimumabDienestrol may increase the thrombogenic activities of Adalimumab.
AducanumabDienestrol may increase the thrombogenic activities of Aducanumab.
AlemtuzumabDienestrol may increase the thrombogenic activities of Alemtuzumab.
Food Interactions
Not Available

Products

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International/Other Brands
Estraguard / Estroral / Ortho Dienestrol (Ortho-McNeil Pharmaceutical) / Restrol / Retalon / Sexadien (LEO Pharma A/S) / Synestrol
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ortho Dienestrol CrmCream.01 %VaginalOrtho Pharmaceutical, Division Of Janssen Ortho Inc.1951-12-312002-08-02Canada flag

Categories

ATC Codes
G03CB01 — DienestrolG03CC02 — Dienestrol
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
RRW32X4U1F
CAS number
13029-44-2
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-[(2E,4E)-4-(4-hydroxyphenyl)hexa-2,4-dien-3-yl]phenol
SMILES
[H]\C(C)=C(/C(=C(\[H])C)/C1=CC=C(O)C=C1)\C1=CC=C(O)C=C1

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
KEGG Drug
D00898
KEGG Compound
C08090
PubChem Compound
667476
PubChem Substance
46504661
ChemSpider
580857
BindingDB
40491
RxNav
3368
ChEBI
4518
ChEMBL
CHEMBL1018
ZINC
ZINC000000001283
Therapeutic Targets Database
DAP001015
PharmGKB
PA164745534
RxList
RxList Drug Page
Wikipedia
Dienestrol
MSDS
Download (75.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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
Polarizability30.27 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 MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kr-0910000000-9291c1e2fa636ec8565e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kr-0090000000-c670775f754081733d9c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-f8c951570ab4a1bc73f8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0960000000-20158229372eeffedefd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-1970000000-53e7cdedced591f88be2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014r-0930000000-b5b9c6a4b6c6205533e1
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-177.0453826
predicted
DarkChem Lite v0.1.0
[M-H]-178.3554
predicted
DeepCCS 1.0 (2019)
[M+H]+177.9022826
predicted
DarkChem Lite v0.1.0
[M+H]+180.7134
predicted
DeepCCS 1.0 (2019)
[M+Na]+187.51936
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  2. Grove RI, Korach KS: Estrogen stimulation of phosphatidylinositol metabolism in mouse uterine tissue. Endocrinology. 1987 Sep;121(3):1083-8. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:45