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	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

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

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

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 127 Target ID: CHEMBL206 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf \| http://www.drugbank.ca/drugs/DB00539	Modulator 828
Thyroid carcinoma cell lines 2 Target ID: Thyroid carcinoma cell lines Sources: https://www.ncbi.nlm.nih.gov/pubmed/9448099	Inhibitor 8297
Muscle-type nicotinic acetylcholine receptor 65 Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9754928	Inhibitor 8297	1.2 µM [IC50]
Zaire ebolavirus 2 Target ID: Zaire ebolavirus Sources: https://www.ncbi.nlm.nih.gov/pubmed/23785035	Inhibitor 8297

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 8429	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/ Page: 175	unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/ Page: 175	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/ Page: 175
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/ Page: 175	unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/ Page: 175	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/ Page: 175
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/ Page: 175	unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/1385761/ Page: 175	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/ Page: 175

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
Toremifene enhances cell cycle block and growth inhibition by vinblastine in multidrug resistant human breast cancer cells.	1993	8123940
Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats.	1993 Oct 1	8402624
Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor promotion in female rats.	1995 Nov	7586193
Structure-activity relationships for triphenylethylene antiestrogens on hepatic phase-I and phase-II enzyme expression.	1998 Aug 1	9744569
Bezafibrate for tamoxifen-induced non-alcoholic steatohepatitis.	1999 May 22	10348023
Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.	2000 Dec	11078796
Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis.	2000 Jul	10959800
Inhibitory effects of toremifene on N-methyl-N-nitrosourea and estradiol-17beta-induced endometrial carcinogenesis in mice.	2002 Jun	12079510
Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer patients.	2003 Nov	14692654
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
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 Feb	25349334
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 Jun	25752796

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 `Fri Dec 15 15:09:55 GMT 2023` Edited by `admin` on `Fri Dec 15 15:09:55 GMT 2023`
Record UNII	2498Y783QT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TOREMIFENE CITRATE

Official 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

FARESTON

Brand 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