Identification
- Generic Name
- Chlorotrianisene
- DrugBank Accession Number
- DB00269
- Background
A powerful synthetic, non-steroidal estrogen. [PubChem]
- Type
- Small Molecule
- Groups
- Investigational, Withdrawn
- Structure
Structure for Chlorotrianisene (DB00269)
- 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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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AEstrogen receptor alpha agonistHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab Chlorotrianisene may decrease the anticoagulant activities of Abciximab. Aceclofenac Aceclofenac may increase the thrombogenic activities of Chlorotrianisene. Acenocoumarol Chlorotrianisene may decrease the anticoagulant activities of Acenocoumarol. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Chlorotrianisene. Adalimumab Chlorotrianisene may increase the thrombogenic activities of Adalimumab. - Food Interactions
- Not Available
Products
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- Merbentul (Merrell) / Tace (Merrell) / Tace FN (Merrell) / Triagen (Gentili)
Categories
- ATC Codes
- G03CA06 — Chlorotrianisene
- Drug Categories
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Benzene Derivatives
- Benzylidene Compounds
- Estrogens
- Estrogens, Non-Steroidal
- Genito Urinary System and Sex Hormones
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Natural and Semisynthetic Estrogens, Plain
- Sex Hormones and Modulators of the Genital System
- Stilbenes
- 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
- External Links
- Human Metabolome Database
- HMDB0014414
- KEGG Drug
- D00269
- PubChem Compound
- 11289
- PubChem Substance
- 46508811
- ChemSpider
- 10815
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
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
Property Value Source melting point (°C) 113-114 REM 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. logP 6.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000199 mg/mL ALOGPS logP 5.95 ALOGPS logP 5.43 Chemaxon logS -6.3 ALOGPS pKa (Strongest Basic) -4.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 27.69 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 119.17 m3·mol-1 Chemaxon Polarizability 40.68 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.651 Caco-2 permeable + 0.8218 P-glycoprotein substrate Non-substrate 0.6283 P-glycoprotein inhibitor I Inhibitor 0.5266 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.8102 CYP450 2C9 substrate Non-substrate 0.7764 CYP450 2D6 substrate Non-substrate 0.8599 CYP450 3A4 substrate Substrate 0.6053 CYP450 1A2 substrate Non-inhibitor 0.8094 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Inhibitor 0.5072 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8625 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.6402 Biodegradation Not ready biodegradable 0.9562 Rat acute toxicity 1.9303 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8429 hERG inhibition (predictor II) Non-inhibitor 0.8456
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 212.234069 predictedDarkChem Lite v0.1.0 [M-H]- 212.012469 predictedDarkChem Lite v0.1.0 [M-H]- 188.99774 predictedDeepCCS 1.0 (2019) [M+H]+ 213.319369 predictedDarkChem Lite v0.1.0 [M+H]+ 212.584069 predictedDarkChem Lite v0.1.0 [M+H]+ 191.35576 predictedDeepCCS 1.0 (2019) [M+Na]+ 211.949369 predictedDarkChem Lite v0.1.0 [M+Na]+ 211.302769 predictedDarkChem Lite v0.1.0 [M+Na]+ 198.42776 predictedDeepCCS 1.0 (2019)
Targets
- 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
- 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]
- 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]
- 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]
- 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
- 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