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
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-;
DescriptionSources: http://www.drugbank.ca/drugs/DB00539Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf
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 | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL206 |
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Target ID: Thyroid carcinoma cell lines Sources: https://www.ncbi.nlm.nih.gov/pubmed/9448099 |
|||
Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9754928 |
1.2 µM [IC50] | ||
Target ID: Zaire ebolavirus Sources: https://www.ncbi.nlm.nih.gov/pubmed/23785035 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FARESTON Approved UseFARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. Launch Date1997 |
Cmax
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 |
T1/2
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: 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: Page: 175 |
DLT: Nausea and vomiting, Dizziness... Other AEs: Sweating, Peripheral edema... Dose limiting toxicities: Nausea and vomiting (grade 1-4, 5 patients) Other AEs:Dizziness (grade 1-4, 4 patients) Sweating (grade 1-4, 3 patients) Sources: Page: 175Peripheral edema (grade 1-4, 3 patients) Vaginal discharge (grade 1-4, 0%) Hot flushes (grade 1-4, 2 patients) |
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: 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: Page: 175 |
Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 7 patients) Sources: Page: 175Dizziness (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) |
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: 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: Page: 175 |
Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 6 patients) Sources: Page: 175Dizziness (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) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Vaginal discharge | grade 1-4, 0% | 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: 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: Page: 175 |
Hot flushes | grade 1-4, 2 patients | 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: 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: Page: 175 |
Peripheral edema | grade 1-4, 3 patients | 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: 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: Page: 175 |
Sweating | grade 1-4, 3 patients | 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: 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: Page: 175 |
Dizziness | grade 1-4, 4 patients DLT |
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: 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: Page: 175 |
Nausea and vomiting | grade 1-4, 5 patients DLT |
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: 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: Page: 175 |
Hot flushes | grade 1-4, 1 patient | 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: 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: Page: 175 |
Dizziness | grade 1-4, 2 patients | 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: 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: Page: 175 |
Peripheral edema | grade 1-4, 2 patients | 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: 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: Page: 175 |
Sweating | grade 1-4, 2 patients | 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: 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: Page: 175 |
Vaginal discharge | grade 1-4, 2 patients | 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: 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: Page: 175 |
Nausea and vomiting | grade 1-4, 7 patients | 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: 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: Page: 175 |
Sweating | grade 1-4, 3 patients | 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: 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: Page: 175 |
Vaginal discharge | grade 1-4, 3 patients | 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: 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: Page: 175 |
Dizziness | grade 1-4, 4 patients | 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: 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: Page: 175 |
Hot flushes | grade 1-4, 4 patients | 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: 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: Page: 175 |
Peripheral edema | grade 1-4, 4 patients | 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: 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: Page: 175 |
Nausea and vomiting | grade 1-4, 6 patients | 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: 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: Page: 175 |
PubMed
Title | Date | PubMed |
---|---|---|
Peroxidase activation of tamoxifen and toremifene resulting in DNA damage and covalently bound protein adducts. | 1995 Mar |
|
Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor promotion in female rats. | 1995 Nov |
|
Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis. | 2000 Jul |
|
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells. | 2004 Dec |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods. | 2006 Nov |
|
In silico prediction of pregnane X receptor activators by machine learning approaches. | 2007 Jan |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8350365
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.
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C1821
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD