Chlorotrianisene

Identification

Generic Name
Chlorotrianisene
DrugBank Accession Number
DB00269
Background

A powerful synthetic, non-steroidal estrogen. [PubChem]

Type
Small Molecule
Groups
Investigational, Withdrawn
Structure
Weight
Average: 380.864
Monoisotopic: 380.117922245
Chemical Formula
C23H21ClO3
Synonyms
  • Chloortrianisestrol
  • Chlorestrolo
  • Chlorotrianisene
  • Chlorotrianisenum
  • Chlorotrianisine
  • Chlorotrianizen
  • Chlortrianisen
  • Chlortrianisestrol
  • Chlortrianisoestrolum
  • Chlortrianizen
  • Clorotrianiseno
External IDs
  • NSC-10108

Pharmacology

Indication

Used to treat symptoms of menopause, deficiencies in ovary function (including underdevelopment of female sexual characteristics and some types of infertility), and in rare cases, prostate cancer. Chlorotrianisene may also be used to prevent breast engorgement following childbirth.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Chlorotrianisene is a nonsteroidal synthetic estrogen. After menopause, when the body no longer produces estrogen, chlorotrianisene is used as a simple replacement of estrogen. The estrogen-stimulated endometrium may bleed within 48-72 hours after discontinuance of estrogen therapy. Paradoxically, prolonged estrogen therapy may cause shrinkage of the endometrium and an increase in size of the myometrium. Estrogens have a weak anabolic effect and may cause sodium retention with associated fluid retention and edema. Estrogens may also decrease elevated blood cholesterol and phospholipid concentrations. Estrogens affect bone by increasing calcium deposition and accelerating epiphyseal closure, following initial growth stimulation. During the preovulatory or nonovulatory phase of the menstrual cycle, estrogen is the principal determinant in the onset of menstruation. A decline of estrogenic activity at the end of the menstrual cycle also may induce menstruation; however, the cessation of progesterone secretion is the most important factor during the mature ovulatory phase of the menstrual cycle. The benefit derived from estrogen therapy in the prevention of postpartum breast engorgement must be carefully weighed against the potential increased risk of puerperal thromboembolism associated with the use of large doses of estrogens.

Mechanism of action

Chlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in 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.

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Humans
Absorption

Absorption following oral administration is rapid.

Volume of distribution

Not Available

Protein binding

50-80%

Metabolism

Metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The metabolic fate of the synthetic estrogens has not been fully elucidated.

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Acute overdosage of large doses of oral contraceptives in chidren reportedly produces almost no toxicity except nausea and vomiting. Acute overdosage of estrogens may cause nausea, 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
AbciximabChlorotrianisene may decrease the anticoagulant activities of Abciximab.
AceclofenacAceclofenac may increase the thrombogenic activities of Chlorotrianisene.
AcenocoumarolChlorotrianisene may decrease the anticoagulant activities of Acenocoumarol.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Chlorotrianisene.
AdalimumabChlorotrianisene may increase the thrombogenic activities of Adalimumab.
Food Interactions
Not Available

Products

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International/Other Brands
Merbentul (Merrell) / Tace (Merrell) / Tace FN (Merrell) / Triagen (Gentili)

Categories

ATC Codes
G03CA06 — Chlorotrianisene
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Diphenylmethanes / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Vinyl chlorides / Chloroalkenes / Organochlorides / Hydrocarbon derivatives
Substituents
Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Benzenoid / Chloroalkene / Diphenylmethane / Ether / Haloalkene / Hydrocarbon derivative / Methoxybenzene
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
chloroalkene (CHEBI:3641)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
6V5034L121
CAS number
569-57-3
InChI Key
BFPSDSIWYFKGBC-UHFFFAOYSA-N
InChI
InChI=1S/C23H21ClO3/c1-25-19-10-4-16(5-11-19)22(17-6-12-20(26-2)13-7-17)23(24)18-8-14-21(27-3)15-9-18/h4-15H,1-3H3
IUPAC Name
1-[2-chloro-1,2-bis(4-methoxyphenyl)ethenyl]-4-methoxybenzene
SMILES
COC1=CC=C(C=C1)C(Cl)=C(C1=CC=C(OC)C=C1)C1=CC=C(OC)C=C1

References

Synthesis Reference

Shelton, R.S. and Van Campen, M.G. Jr.; U S . Patent 2,430,891; November 18,1947; assigned to the Wm. S. Merrell Company.

General References
Not Available
Human Metabolome Database
HMDB0014414
KEGG Drug
D00269
PubChem Compound
11289
PubChem Substance
46508811
ChemSpider
10815
RxNav
2397
ChEBI
3641
ChEMBL
CHEMBL1200761
ZINC
ZINC000001530598
Therapeutic Targets Database
DAP001012
PharmGKB
PA164768822
Drugs.com
Drugs.com Drug Page
Wikipedia
Chlorotrianisene

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Banner pharmacaps inc
  • Sanofi aventis us llc
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)113-114REM p.988 Shelton, R.S. and Van Campen, M.G. Jr.; U S . Patent 2,430,891; November 18,1947; assigned to the Wm. S. Merrell Company.
logP6.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000199 mg/mLALOGPS
logP5.95ALOGPS
logP5.43Chemaxon
logS-6.3ALOGPS
pKa (Strongest Basic)-4.4Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area27.69 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity119.17 m3·mol-1Chemaxon
Polarizability40.68 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.651
Caco-2 permeable+0.8218
P-glycoprotein substrateNon-substrate0.6283
P-glycoprotein inhibitor IInhibitor0.5266
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8102
CYP450 2C9 substrateNon-substrate0.7764
CYP450 2D6 substrateNon-substrate0.8599
CYP450 3A4 substrateSubstrate0.6053
CYP450 1A2 substrateNon-inhibitor0.8094
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.5072
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8625
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6402
BiodegradationNot ready biodegradable0.9562
Rat acute toxicity1.9303 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8429
hERG inhibition (predictor II)Non-inhibitor0.8456
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00p1-0149000000-13ed744e89313692e56d
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-3900000000-f12188734d2d15075e1a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0012-1495000000-9f658a59776206767e09
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0009000000-43e703c002a5abf94b65
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-1009000000-fa3e8c7d6b478aced07e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-0609000000-6f918524072f252e83b3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9003000000-13d35c0b1d0c25ab4d2d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-008i-0934000000-5220dd48a78578b210d8
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-44420165bf0cd98161ae
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]-212.234069
predicted
DarkChem Lite v0.1.0
[M-H]-212.012469
predicted
DarkChem Lite v0.1.0
[M-H]-188.99774
predicted
DeepCCS 1.0 (2019)
[M+H]+213.319369
predicted
DarkChem Lite v0.1.0
[M+H]+212.584069
predicted
DarkChem Lite v0.1.0
[M+H]+191.35576
predicted
DeepCCS 1.0 (2019)
[M+Na]+211.949369
predicted
DarkChem Lite v0.1.0
[M+Na]+211.302769
predicted
DarkChem Lite v0.1.0
[M+Na]+198.42776
predicted
DeepCCS 1.0 (2019)

Targets

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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. Kupfer D, Bulger WH: Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. FEBS Lett. 1990 Feb 12;261(1):59-62. [Article]
  2. Jordan VC, Gosden B: Inhibition of the uterotropic activity of estrogens and antiestrogens by the short acting antiestrogen LY117018. Endocrinology. 1983 Aug;113(2):463-8. [Article]
  3. Wang JY, Xu BH, Tian LJ, Wang Y: [Clinical characteristics and potential prognostic factors of breast cancer patients with liver metastases]. Zhonghua Zhong Liu Za Zhi. 2006 Aug;28(8):612-6. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Adashi EY, Hsueh AJ: Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. J Biol Chem. 1982 Jun 10;257(11):6077-83. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:44