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Details

Stereochemistry ACHIRAL
Molecular Formula C26H29NO
Molecular Weight 371.5146
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TAMOXIFEN

SMILES

CC\C(C1=CC=CC=C1)=C(/C2=CC=CC=C2)C3=CC=C(OCCN(C)C)C=C3

InChI

InChIKey=NKANXQFJJICGDU-QPLCGJKRSA-N
InChI=1S/C26H29NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18H,4,19-20H2,1-3H3/b26-25-

HIDE SMILES / InChI

Molecular Formula C26H29NO
Molecular Weight 371.5146
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00675 | https://www.ncbi.nlm.nih.gov/pubmed/18316672 | https://www.ncbi.nlm.nih.gov/pubmed/2021551 | https://www.drugs.com/tamoxifen.html | http://reference.medscape.com/drug/soltamox-tamoxifen-342183

Tamoxifen (brand name Nolvadex), is selective estrogen receptor modulators (SERM) with tissue-specific activities for the treatment and prevention of estrogen receptor positive breast cancer. Tamoxifen itself is a prodrug, having relatively little affinity for its target protein, the estrogen receptor (ER). It is metabolized in the liver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen (4-OHT) (afimoxifene) and N-desmethyl-4-hydroxytamoxifen (endoxifen) which have 30–100 times more affinity with the ER than tamoxifen itself. These active metabolites compete with estrogen in the body for binding to the ER. In breast tissue, 4-OHT acts as an ER antagonist so that transcription of estrogen-responsive genes is inhibited. Tamoxifen has 7% and 6% of the affinity of estradiol for the ERα and ERβ, respectively, whereas 4-OHT has 178% and 338% of the affinity of estradiol for the ERα and ERβ. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects. Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER)-positive (ER+) breast cancer in pre- and post-menopausal women. Additionally, it is the most common hormone treatment for male breast cancer. Patients with variant forms of the gene CYP2D6 (also called simply 2D6) may not receive full benefit from tamoxifen because of too slow metabolism of the tamoxifen prodrug into its active metabolites. Tamoxifen is used as a research tool to trigger tissue-specific gene expression in many conditional expression constructs in genetically modified animals including a version of the Cre-Lox recombination technique. Tamoxifen has been shown to be effective in the treatment of mania in patients with bipolar disorder by blocking protein kinase C (PKC), an enzyme that regulates neuron activity in the brain. Researchers believe PKC is over-active during the mania in bipolar patients.

CNS Activity

Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/18316672

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
39.0 nM [IC50]
1660.0 nM [IC50]
580.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NOLVADEX

Approved Use

Metastatic Breast Cancer Tamoxifen citrate tablets are effective in the treatment of metastatic breast cancer in women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation. Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy. Adjuvant Treatment of Breast Cancer Tamoxifen citrate tablets are indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes. Tamoxifen citrate tablets are indicated for the treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial. Tamoxifen reduces the occurrence of contralateral breast cancer in patients receiving adjuvant tamoxifen therapy for breast cancer. Ductal Carcinoma in Situ (DCIS) In women with DCIS, following breast surgery and radiation, tamoxifen citrate tablets are indicated to reduce the risk of invasive breast cancer (see BOXED WARNING at the beginning of the label). The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer. Reduction in Breast Cancer Incidence in High Risk Women Tamoxifen citrate tablets are indicated to reduce the incidence of breast cancer in women at high risk for breast cancer. This effect was shown in a study of 5 years planned duration with a median follow-up of 4.2 years. Twenty-five percent of the participants received drug for 5 years. The longer-term effects are not known. In this study, there was no impact of tamoxifen on overall or breast cancer-related mortality (see BOXED WARNING at the beginning of the label). Tamoxifen citrate tablets are indicated only for high-risk women. “High risk” is defined as women at least 35 years of age with a 5 year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. Examples of combinations of factors predicting a 5 year risk ≥ 1.67% are: Age 35 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, and a history of a breast biopsy showing atypical hyperplasia; or •At least 2 first degree relatives with a history of breast cancer, and a personal history of at least 1 breast biopsy; or •LCIS Age 40 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, age at first live birth 25 or older, and age at menarche 11 or younger; or •At least 2 first degree relatives with a history of breast cancer, and age at first live birth 19 or younger; or •One first degree relative with a history of breast cancer, and a personal history of a breast biopsy showing atypical hyperplasia. Age 45 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer and age at first live birth 24 or younger; or •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, age at menarche 11 or less and age at first live birth 20 or more. Age 50 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer; or •History of 1 breast biopsy showing atypical hyperplasia, and age at first live birth 30 or older and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 30 or more. Age 55 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 20 or older. Age 60 or older and: •Five-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. For women whose risk factors are not described in the above examples, the Gail Model is necessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-888-838-2872. There are insufficient data available regarding the effect of tamoxifen on breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of tamoxifen in these patients. After an assessment of the risk of developing breast cancer, the decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. In the NSABP P-1 trial, tamoxifen treatment lowered the risk of developing breast cancer during the follow-up period of the trial, but did not eliminate breast cancer risk (see Table 3 in CLINICAL PHARMACOLOGY ).

Launch Date

2.52288008E11
Preventing
NOLVADEX

Approved Use

Metastatic Breast Cancer Tamoxifen citrate tablets are effective in the treatment of metastatic breast cancer in women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation. Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy. Adjuvant Treatment of Breast Cancer Tamoxifen citrate tablets are indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes. Tamoxifen citrate tablets are indicated for the treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial. Tamoxifen reduces the occurrence of contralateral breast cancer in patients receiving adjuvant tamoxifen therapy for breast cancer. Ductal Carcinoma in Situ (DCIS) In women with DCIS, following breast surgery and radiation, tamoxifen citrate tablets are indicated to reduce the risk of invasive breast cancer (see BOXED WARNING at the beginning of the label). The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer. Reduction in Breast Cancer Incidence in High Risk Women Tamoxifen citrate tablets are indicated to reduce the incidence of breast cancer in women at high risk for breast cancer. This effect was shown in a study of 5 years planned duration with a median follow-up of 4.2 years. Twenty-five percent of the participants received drug for 5 years. The longer-term effects are not known. In this study, there was no impact of tamoxifen on overall or breast cancer-related mortality (see BOXED WARNING at the beginning of the label). Tamoxifen citrate tablets are indicated only for high-risk women. “High risk” is defined as women at least 35 years of age with a 5 year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. Examples of combinations of factors predicting a 5 year risk ≥ 1.67% are: Age 35 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, and a history of a breast biopsy showing atypical hyperplasia; or •At least 2 first degree relatives with a history of breast cancer, and a personal history of at least 1 breast biopsy; or •LCIS Age 40 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, age at first live birth 25 or older, and age at menarche 11 or younger; or •At least 2 first degree relatives with a history of breast cancer, and age at first live birth 19 or younger; or •One first degree relative with a history of breast cancer, and a personal history of a breast biopsy showing atypical hyperplasia. Age 45 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer and age at first live birth 24 or younger; or •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, age at menarche 11 or less and age at first live birth 20 or more. Age 50 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer; or •History of 1 breast biopsy showing atypical hyperplasia, and age at first live birth 30 or older and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 30 or more. Age 55 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 20 or older. Age 60 or older and: •Five-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. For women whose risk factors are not described in the above examples, the Gail Model is necessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-888-838-2872. There are insufficient data available regarding the effect of tamoxifen on breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of tamoxifen in these patients. After an assessment of the risk of developing breast cancer, the decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. In the NSABP P-1 trial, tamoxifen treatment lowered the risk of developing breast cancer during the follow-up period of the trial, but did not eliminate breast cancer risk (see Table 3 in CLINICAL PHARMACOLOGY ).

Launch Date

2.52288008E11
Primary
NOLVADEX

Approved Use

Metastatic Breast Cancer Tamoxifen citrate tablets are effective in the treatment of metastatic breast cancer in women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation. Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy. Adjuvant Treatment of Breast Cancer Tamoxifen citrate tablets are indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes. Tamoxifen citrate tablets are indicated for the treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial. Tamoxifen reduces the occurrence of contralateral breast cancer in patients receiving adjuvant tamoxifen therapy for breast cancer. Ductal Carcinoma in Situ (DCIS) In women with DCIS, following breast surgery and radiation, tamoxifen citrate tablets are indicated to reduce the risk of invasive breast cancer (see BOXED WARNING at the beginning of the label). The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer. Reduction in Breast Cancer Incidence in High Risk Women Tamoxifen citrate tablets are indicated to reduce the incidence of breast cancer in women at high risk for breast cancer. This effect was shown in a study of 5 years planned duration with a median follow-up of 4.2 years. Twenty-five percent of the participants received drug for 5 years. The longer-term effects are not known. In this study, there was no impact of tamoxifen on overall or breast cancer-related mortality (see BOXED WARNING at the beginning of the label). Tamoxifen citrate tablets are indicated only for high-risk women. “High risk” is defined as women at least 35 years of age with a 5 year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. Examples of combinations of factors predicting a 5 year risk ≥ 1.67% are: Age 35 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, and a history of a breast biopsy showing atypical hyperplasia; or •At least 2 first degree relatives with a history of breast cancer, and a personal history of at least 1 breast biopsy; or •LCIS Age 40 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer, 2 or more benign biopsies, age at first live birth 25 or older, and age at menarche 11 or younger; or •At least 2 first degree relatives with a history of breast cancer, and age at first live birth 19 or younger; or •One first degree relative with a history of breast cancer, and a personal history of a breast biopsy showing atypical hyperplasia. Age 45 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer and age at first live birth 24 or younger; or •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, age at menarche 11 or less and age at first live birth 20 or more. Age 50 or older and any of the following combination of factors: •At least 2 first degree relatives with a history of breast cancer; or •History of 1 breast biopsy showing atypical hyperplasia, and age at first live birth 30 or older and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 30 or more. Age 55 or older and any of the following combination of factors: •One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, and age at menarche 11 or less; or •History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 20 or older. Age 60 or older and: •Five-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. For women whose risk factors are not described in the above examples, the Gail Model is necessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-888-838-2872. There are insufficient data available regarding the effect of tamoxifen on breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of tamoxifen in these patients. After an assessment of the risk of developing breast cancer, the decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. In the NSABP P-1 trial, tamoxifen treatment lowered the risk of developing breast cancer during the follow-up period of the trial, but did not eliminate breast cancer risk (see Table 3 in CLINICAL PHARMACOLOGY ).

Launch Date

2.52288008E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
63.6 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAMOXIFEN blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
187 ng/mL
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TAMOXIFEN plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3370.1 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAMOXIFEN blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
4110 ng × h/mL
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TAMOXIFEN plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
209.8 h
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAMOXIFEN blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (grade 1-4)
Vomiting (grade 1-4)
Dizziness (grade 1-4)
Unsteadiness (grade 1-4)
Malaise (grade 1-4)
Sources:
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Other AEs: Neutropenia, Thrombocytopenia...
Other AEs:
Neutropenia (grade 4, 10%)
Thrombocytopenia (grade 2, 10%)
Hemoglobin decreased
Serum creatinine increased
Sources:
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
DLT: Neutropenia, Thrombocytopenia...
Disc. AE: Nausea, Vomiting...
Other AEs: Serum creatinine increased...
Dose limiting toxicities:
Neutropenia (grade 4, 22.2%)
Thrombocytopenia (grade 4, 22.2%)
AEs leading to
discontinuation/dose reduction:
Nausea (11.1%)
Vomiting (11.1%)
Anorexia (11.1%)
Septicemia (11.1%)
Other AEs:
Serum creatinine increased (11.1%)
Sources:
30 mg 2 times / day multiple, oral
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 74
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 74
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (grade 3, 1.3%)
Vomiting (grade 3, 1.3%)
Sources:
60 mg 2 times / day multiple, oral
Studied dose
Dose: 60 mg, 2 times / day
Route: oral
Route: multiple
Dose: 60 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 120
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 120
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (grade 3, 0.8%)
Vomiting (grade 3, 0.8%)
Sources:
10 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 902
Other AEs: Uterine neoplasms malignant NEC, Stroke...
700 mg 1 times / day multiple, oral
Highest studied dose
Dose: 700 mg, 1 times / day
Route: oral
Route: multiple
Dose: 700 mg, 1 times / day
Co-administed with::
daunorubicin(50 mg/m2 intravenously on days 5, 6 and 7)
Sources:
unhealthy, median age 50 years
n = 3
Health Status: unhealthy
Condition: acute leukemia
Age Group: median age 50 years
Sex: M+F
Population Size: 3
Sources:
100 mg/m2 2 times / day multiple, oral
MTD
Dose: 100 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 3
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 3
Sources:
Other AEs: Mental status changes...
Other AEs:
Mental status changes (grade 3, 33.3%)
Sources:
125 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 125 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 6
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 6
Sources:
DLT: Thrombocytopenia...
Other AEs: QT interval prolonged, Thrombosis venous deep...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 16.7%)
Other AEs:
QT interval prolonged (16.7%)
Thrombosis venous deep (16.7%)
Sources:
75 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 75 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 75 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Other AEs: Thrombosis venous deep...
Other AEs:
Thrombosis venous deep (grade 3, 25%)
Sources:
680 mg/m2 1 times / day single, oral
Highest studied dose
Dose: 680 mg/m2, 1 times / day
Route: oral
Route: single
Dose: 680 mg/m2, 1 times / day
Co-administed with::
Vinblastine(1.5 mg/m2 per day intravenous; on days 9-13)
Sources:
unhealthy, median age 58 years
n = 3
Health Status: unhealthy
Condition: epithelial tumors
Age Group: median age 58 years
Population Size: 3
Sources:
230 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 230 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 230 mg/m2, 2 times / day
Co-administed with::
Vinblastine(1.5 mg/m2 per day intravenous; on days 9-13)
Sources:
unhealthy, median age 58 years
n = 3
Health Status: unhealthy
Condition: epithelial tumors
Age Group: median age 58 years
Population Size: 3
Sources:
DLT: Grand mal seizure...
Dose limiting toxicities:
Grand mal seizure (33.3%)
Sources:
250 mg/m2 multiple, oral (starting)
Studied dose
Dose: 250 mg/m2
Route: oral
Route: multiple
Dose: 250 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Other AEs: QT interval prolonged...
400 mg/m2 multiple, oral (starting)
Studied dose
Dose: 400 mg/m2
Route: oral
Route: multiple
Dose: 400 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Other AEs: Tremor, Hyperreflexia...
Other AEs:
Tremor
Hyperreflexia
Unsteady gait
Dizziness
Sources:
AEs

AEs

AESignificanceDosePopulation
Dizziness grade 1-4
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Malaise grade 1-4
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Nausea grade 1-4
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Unsteadiness grade 1-4
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Vomiting grade 1-4
240 mg 3 times / day multiple, oral
MTD
Dose: 240 mg, 3 times / day
Route: oral
Route: multiple
Dose: 240 mg, 3 times / day
Co-administed with::
etoposide(300 mg orally; day-1 for 3 days)
Sources:
unhealthy, Median age 50 years
n = 16
Health Status: unhealthy
Condition: cancer
Age Group: Median age 50 years
Sex: M+F
Population Size: 16
Sources:
Hemoglobin decreased
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Serum creatinine increased
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Thrombocytopenia grade 2, 10%
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Neutropenia grade 4, 10%
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Serum creatinine increased 11.1%
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Anorexia 11.1%
Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Nausea 11.1%
Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Septicemia 11.1%
Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Vomiting 11.1%
Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Neutropenia grade 4, 22.2%
DLT, Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Thrombocytopenia grade 4, 22.2%
DLT, Disc. AE
280 mg 1 times / day multiple, oral
Studied dose
Dose: 280 mg, 1 times / day
Route: oral
Route: multiple
Dose: 280 mg, 1 times / day
Co-administed with::
cisplatin(80 mg/m2 intravenous; once weekly)
Sources:
unhealthy, Median age 53 years
n = 3
Health Status: unhealthy
Condition: metastatic melanoma
Age Group: Median age 53 years
Sex: M+F
Population Size: 3
Sources:
Nausea grade 3, 1.3%
30 mg 2 times / day multiple, oral
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 74
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 74
Sources:
Vomiting grade 3, 1.3%
30 mg 2 times / day multiple, oral
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 74
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 74
Sources:
Nausea grade 3, 0.8%
60 mg 2 times / day multiple, oral
Studied dose
Dose: 60 mg, 2 times / day
Route: oral
Route: multiple
Dose: 60 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 120
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 120
Sources:
Vomiting grade 3, 0.8%
60 mg 2 times / day multiple, oral
Studied dose
Dose: 60 mg, 2 times / day
Route: oral
Route: multiple
Dose: 60 mg, 2 times / day
Sources:
unhealthy, Median age 61 years
n = 120
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: Median age 61 years
Sex: M+F
Population Size: 120
Sources:
Pulmonary embolism
10 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 902
Stroke
10 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 902
Uterine neoplasms malignant NEC
10 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 902
Mental status changes grade 3, 33.3%
100 mg/m2 2 times / day multiple, oral
MTD
Dose: 100 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 3
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 3
Sources:
QT interval prolonged 16.7%
125 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 125 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 6
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 6
Sources:
Thrombosis venous deep 16.7%
125 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 125 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 6
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 6
Sources:
Thrombocytopenia grade 4, 16.7%
DLT
125 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 125 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 6
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 6
Sources:
Thrombosis venous deep grade 3, 25%
75 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 75 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 75 mg/m2, 2 times / day
Co-administed with::
temozolomide(75 mg/m2 orally; 6 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: high-grade glioma
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Grand mal seizure 33.3%
DLT
230 mg/m2 2 times / day multiple, oral
Studied dose
Dose: 230 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 230 mg/m2, 2 times / day
Co-administed with::
Vinblastine(1.5 mg/m2 per day intravenous; on days 9-13)
Sources:
unhealthy, median age 58 years
n = 3
Health Status: unhealthy
Condition: epithelial tumors
Age Group: median age 58 years
Population Size: 3
Sources:
QT interval prolonged
250 mg/m2 multiple, oral (starting)
Studied dose
Dose: 250 mg/m2
Route: oral
Route: multiple
Dose: 250 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Dizziness
400 mg/m2 multiple, oral (starting)
Studied dose
Dose: 400 mg/m2
Route: oral
Route: multiple
Dose: 400 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Hyperreflexia
400 mg/m2 multiple, oral (starting)
Studied dose
Dose: 400 mg/m2
Route: oral
Route: multiple
Dose: 400 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Tremor
400 mg/m2 multiple, oral (starting)
Studied dose
Dose: 400 mg/m2
Route: oral
Route: multiple
Dose: 400 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
Unsteady gait
400 mg/m2 multiple, oral (starting)
Studied dose
Dose: 400 mg/m2
Route: oral
Route: multiple
Dose: 400 mg/m2
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced metastatic cancer
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
yes [EC50 0.178 uM]
yes [EC50 0.187 uM]
yes [EC50 0.3 uM]
yes [EC50 0.4 uM]
yes [EC50 0.488 uM]
yes [EC50 0.518 uM]
yes [IC50 0.21 uM]
yes [IC50 0.32 uM]
yes [IC50 2.4 uM]
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
unknown (co-administration study)
Comment: Although concomitant administration of CYP2D6 inhibitors reduces the plasma concentration of endoxifen, a potent metabolite, the clinical significance is not well established [see Drug Interactions (7.4)]. The mean steady-state endoxifen plasma concentration in patients taking CYP2D6 inhibitors was significantly reduced compared to those not taking concomitant CYP2D6 inhibitors (14.8 ± 10.6 versus 26.7 ± 15.4 ng/mL). The mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors was 31.4 ± 14.7 ng/mL compared to 8.8 ± 3.5 ng/mL in CYP2D6 normal metabolizers receiving potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) with tamoxifen. The plasma levels of endoxifen in CYP2D6 normal metabolizers taking potent CYP2D6 inhibitors were similar to the levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors (8.8 versus 7.2 ng/mL).
Page: 15.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study.
1999
Life-threatening tamoxifen-induced hypercalcaemia.
1999
Ocular toxicity in low-dose tamoxifen: a prospective study.
1999 Dec
[Fatal hypercalcemia in tamoxifen. Chief symptom: increasing somnolence in a 68-year-old patient].
1999 Nov 11
The Italian Tamoxifen Prevention Trial.
1999 Oct
Non-alcoholic steatohepatitis.
1999 Oct 9
The relationship of tamoxifen with dementia, depression, and dependence in activities of daily living in elderly nursing home residents.
2000
A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea--a review.
2000
The effects of tamoxifen therapy on the endometrium.
2000
The endometrium in breast cancer patients on tamoxifen.
2000 Apr
Acquired cystic kidney disease: rapid progression from small to enlarged kidneys simulating adult polycystic kidney disease.
2000 Apr
Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer.
2000 Apr 15
The interferon-beta and tamoxifen combination induces apoptosis using thioredoxin reductase.
2000 Apr 17
[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].
2000 Aug
[Endometrial adenocarcinoma appearing during tamoxifen therapy. Report of a clinical case].
2000 Dec
Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.
2000 Dec
Proteinase inhibitor 9, an inhibitor of granzyme B-mediated apoptosis, is a primary estrogen-inducible gene in human liver cells.
2000 Feb 25
Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis.
2000 Jul
Acute onset of auditory hallucinations after initiation of celecoxib therapy.
2000 Jun
Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.
2000 Mar 15
Occurrence of stroke with tamoxifen in NSABP B-24.
2000 Mar 4
Effective tamoxifen therapy of breast cancer involves both antiproliferative and pro-apoptotic changes.
2000 May
Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen.
2000 Nov
[Cirrhosis with non alcoholic steatohepatitis: role of tamoxifen].
2000 Nov
Differential estrogen receptor binding of estrogenic substances: a species comparison.
2000 Nov 15
Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients.
2000 Nov-Dec
Hepatocellular carcinoma after long-term tamoxifen therapy.
2000 Sep
Drug approval summaries: arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene.
2001
Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists.
2001 Feb
Tamoxifen and cardiac risk factors in healthy women: Suggestion of an anti-inflammatory effect.
2001 Feb
In vivo regulation of syndecan-3 expression in the rat uterus by 17 beta-estradiol.
2001 Jan 5
Combination chemotherapy of cisplatin, methotrexate, vinblastine, and high-dose tamoxifen for transitional cell carcinoma.
2001 Jan-Feb
Detection of endometrial cancer in asymptomatic postmenopausal breast cancer patient treated with tamoxifen: a case report.
2001 Jul
4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma.
2001 Jul 17
Cell response endpoints enhance sensitivity of the immature mouse uterotropic assay.
2001 May-Jun
A case with cerebral thrombosis receiving tamoxifen treatment.
2001 Nov
Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.
2001 Nov-Dec
Tamoxifen-induced cirrhotic process.
2001 Nov-Dec
Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.
2002 Dec
[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 Jan
Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites.
2002 Oct
Chemoimmunohormonal therapy with carmustine, dacarbazine, cisplatin, tamoxifen, and interferon for metastatic melanoma: a prospective phase II study.
2002 Oct
In vitro antiestrogenic effects of aryl methyl sulfone metabolites of polychlorinated biphenyls and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene on 17beta-estradiol-induced gene expression in several bioassay systems.
2002 Oct
Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites.
2003 Apr
Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand.
2003 Apr
Comparison of the reporter gene assay for ER-alpha antagonists with the immature rat uterotrophic assay of 10 chemicals.
2003 Apr 30
Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 actions in human breast cancer cells.
2003 Feb
Inhibition of TNF-alpha-induced RANTES expression in human hepatocyte-derived cells by fibrates, the hypolipidemic drugs.
2003 Feb
The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen.
2003 Mar-Apr
Extensive pelvic endometriosis with malignant change in tamoxifen-treated postmenopausal women.
2003 May-Jun
Patents

Sample Use Guides

For patients with breast cancer, the recommended daily dose is 20-40 mg. Dosages greater than 20 mg per day should be given in divided doses (morning and evening).
Route of Administration: Oral
HELNalpha and HELNbeta two human cervix adenocarcinoma cell lines derived from HeLa cells stably transfected with the reporter gene ERE-betaGlob-Luc-SVNeo and the expression plasmids ERalpha or ERbeta respectively, were used to quantify the antiestrogenic and estrogenic effects of Tamoxifen. These cells were routinely cultivated in DMEM phenol red free, supplemented with 5% sFBS, 2 mM glutamine, 1% penicillin/streptomycin, 1 mg/mL Geneticin, and 0.5 mkg/mL puromycin to ensure appropriate antibiotic selection. For the assay, cells were trypsinized from the maintenance flask with phenol red free trypsin (0.05%)-EDTA (0.02%) (HyClone, Logan, UT) and seeded in an opaque 96-well plate (Nunc) at a density of 7.5 x 10^4 cells/well in a final volume of 100 mkL of assay medium (DMEM, phenol red free, supplemented with 3% sFBS, 2 mM glutamine, and penicillin/streptomycin). Five hours later, cells were adherent. Serial dilutions of Tamoxifen or DMSO as diluent control were then added in the presence of a fixed concentration of 17beta-estradiol (10^-10 M in HELNalpha and 10^-9 M in HELNbeta) to triplicate microcultures. Faslodex (Tocris, 10^-8 M) was used as a baseline indicator. Cells were incubated for 20 h at 37 °C in a 5% CO2 humidified incubator before being processed for luciferase determination. Medium was aspirated and 100 mkL of a 1:1 mixture of LucLite (Perkin-Elmer, Life Science, Boston, MA)/assay medium was added to each well. Plates were then sealed with a Topseal and left in the dark for 10 min before luminescence activity was determined by counting the plates for 6 s in a beta-TopCount (Packard Instrument Company, Meriden, CT).
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:01:40 UTC 2023
Edited
by admin
on Wed Jul 05 23:01:40 UTC 2023
Record UNII
094ZI81Y45
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAMOXIFEN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
TAMOXIFEN [HSDB]
Common Name English
TAMOPLEX
Brand Name English
Tamoxifen [WHO-DD]
Common Name English
ICI-47699
Code English
tamoxifen [INN]
Common Name English
NOVALDEX
Brand Name English
NSC-727681
Code English
TAMOXIFEN [IARC]
Common Name English
(Z)-2-(4-(1,2-DIPHENYL-1-BUTENYL)PHENOXY)-N,N-DIMETHYLETHANAMINE
Systematic Name English
ETHANAMINE, 2-(4-((1Z)-1,2-DIPHENYL-1-BUTEN-1-YL)PHENOXY)-N,N-DIMETHYL-
Systematic Name English
TAMOXIFEN [VANDF]
Common Name English
MAMMATON
Brand Name English
TAMOXIFEN [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC L02BA01
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
LIVERTOX NBK548902
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
NCI_THESAURUS C1821
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
NCI_THESAURUS C2089
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 8.3
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
NDF-RT N0000175826
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
NDF-RT N0000000168
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
WHO-VATC QL02BA01
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
Code System Code Type Description
MERCK INDEX
M10450
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY Merck Index
LACTMED
Tamoxifen
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
HSDB
6782
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
INN
3299
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
EVMPD
SUB10825MIG
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
FDA UNII
094ZI81Y45
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
RXCUI
10324
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID1034187
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
MESH
D013629
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
DRUG CENTRAL
2561
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
DRUG BANK
DB00675
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
CAS
10540-29-1
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
NSC
727681
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
WIKIPEDIA
TAMOXIFEN
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
ECHA (EC/EINECS)
234-118-0
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
CHEBI
41774
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
PUBCHEM
2733526
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
IUPHAR
1016
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
DAILYMED
094ZI81Y45
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
ChEMBL
CHEMBL83
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
NCI_THESAURUS
C62078
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
SMS_ID
100000091546
Created by admin on Wed Jul 05 23:01:40 UTC 2023 , Edited by admin on Wed Jul 05 23:01:40 UTC 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Binding Assay
IC50
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
IC50
TARGET -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC