TOREMIFENE CITRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H28ClNO.C6H8O7
Molecular Weight	598.083
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.CN(C)CCOC1=CC=C(C=C1)C(=C(\CCCl)C2=CC=CC=C2)\C3=CC=CC=C3

InChI

InChIKey=IWEQQRMGNVVKQW-OQKDUQJOSA-N

InChI=1S/C26H28ClNO.C6H8O7/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-16H,17-20H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b26-25-;

HIDE SMILES / InChI

Molecular Formula	C26H28ClNO
Molecular Weight	405.96
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00539
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf

Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein. Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors. Toremifene is used for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer. Toremifene is marketed in the United States under the brand name Fareston.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor alpha 134 Target ID: CHEMBL206 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf \| http://www.drugbank.ca/drugs/DB00539	Modulator 846
Thyroid carcinoma cell lines 2 Target ID: Thyroid carcinoma cell lines Sources: https://www.ncbi.nlm.nih.gov/pubmed/9448099	Inhibitor 8504
Muscle-type nicotinic acetylcholine receptor 65 Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9754928	Inhibitor 8504	1.2 µM [IC50]
Zaire ebolavirus 2 Target ID: Zaire ebolavirus Sources: https://www.ncbi.nlm.nih.gov/pubmed/23785035	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic breast cancer 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf	Primary		Approved 8583	FARESTON Approved Use FARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
414 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
722 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
28.4 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
34.1 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.2 day EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
99 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		TOREMIFENE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	unhealthy, 38 - 79 years Health Status: unhealthy Age Group: 38 - 79 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	DLT: Nausea and vomiting, Dizziness... Other AEs: Sweating, Peripheral edema... Dose limiting toxicities: Nausea and vomiting (grade 1-4, 5 patients) Dizziness (grade 1-4, 4 patients) Other AEs: Sweating (grade 1-4, 3 patients) Peripheral edema (grade 1-4, 3 patients) Vaginal discharge (grade 1-4, 0%) Hot flushes (grade 1-4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/
200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	unhealthy, 38 - 79 years Health Status: unhealthy Age Group: 38 - 79 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 7 patients) Dizziness (grade 1-4, 2 patients) Sweating (grade 1-4, 2 patients) Peripheral edema (grade 1-4, 2 patients) Vaginal discharge (grade 1-4, 2 patients) Hot flushes (grade 1-4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/
300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	unhealthy, 38 - 79 years Health Status: unhealthy Age Group: 38 - 79 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/	Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 6 patients) Dizziness (grade 1-4, 4 patients) Sweating (grade 1-4, 3 patients) Peripheral edema (grade 1-4, 4 patients) Vaginal discharge (grade 1-4, 3 patients) Hot flushes (grade 1-4, 4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9635	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9635
ChemicalBook	CB0287854	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0287854
ZINC	ZINC000012404516	http://zinc15.docking.org/substances/ZINC000012404516

PubMed

Title	Date	PubMed
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.	2015-06	25752796
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.	2015-02	25349334
Chemoprevention of prostate cancer: agents and study designs.	2007-09	17644117
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007-01	17003167
Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs).	2007	17504144
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006-11	16497524
Histopathology and histomorphometry of the urogenital tract in 15-month old male and female rats treated neonatally with SERMs and estrogens.	2006-08	16709447
Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy.	2006-03	16503765
Estrogen receptors as therapeutic targets in breast cancer.	2006	16515478
Drug resistance in chemotherapy for breast cancer.	2005-11	16273361
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005-06	15962942
Role of 5a-reductase inhibitors and selective estrogen receptor modulators as potential chemopreventive agents for prostate cancer.	2005-03	15882476
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells.	2004-12	15316697
Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer patients.	2003-11	14692654
Inhibitory effects of toremifene on N-methyl-N-nitrosourea and estradiol-17beta-induced endometrial carcinogenesis in mice.	2002-06	12079510
[A case of locally recurrent breast cancer in which phlebothrombosis of the right leg after hormonal therapy using a high dose of toremifene citrate].	2002-01	11816466
Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.	2000-12	11078796
Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis.	2000-07	10959800
Bezafibrate for tamoxifen-induced non-alcoholic steatohepatitis.	1999-05-22	10348023
Structure-activity relationships for triphenylethylene antiestrogens on hepatic phase-I and phase-II enzyme expression.	1998-08-01	9744569
A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats.	1996-11	8972233
Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor promotion in female rats.	1995-11	7586193
Peroxidase activation of tamoxifen and toremifene resulting in DNA damage and covalently bound protein adducts.	1995-03	7697811
Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats.	1993-10-01	8402624
Toremifene enhances cell cycle block and growth inhibition by vinblastine in multidrug resistant human breast cancer cells.	1993	8123940

Patents

Sample Use Guides

In Vivo Use Guide

60 mg once daily, orally

Route of Administration: Oral

In Vitro Use Guide

Treatment of the human breast cancer cell line MCF-7 with 7.5 uM toremifene for 3 days caused approximately 60% of the cells to exhibit morphologic characteristics typical of cells undergoing apoptosis.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:48:42 GMT 2025` Edited by `admin` on `Mon Mar 31 17:48:42 GMT 2025`
Record UNII	2498Y783QT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TOREMIFENE CITRATE

Official Name

English

FARESTON

Preferred Name

English

Toremifene citrate [WHO-DD]

Common Name

English

2-[P-[(Z)-4-Chloro-1,2-diphenyl-1-butenyl]phenoxy]-N,N-dimethylethylamine citrate (1:1)

Common Name

English

TOREMIFENE CITRATE [ORANGE BOOK]

Common Name

English

FC-1157A

Code

English

TOREMIFENE CITRATE [MART.]

Common Name

English

ETHANAMINE, 2-(4-(4-CHLORO-1,2-DIPHENYL-1-BUTENYL)PHENOXY)-N,N-DIMETHYL-, (Z)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)

Common Name

English

TOREMIFENE CITRATE [VANDF]

Common Name

English

TOREMIFENE CITRATE [MI]

Common Name

English

TOREMIFENE CITRATE [USAN]

Common Name

English

TOREMIFENE CITRATE [JAN]

Common Name

English

NSC-613680

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1821