Active Ingredient History
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. NCATS
Drug Pricing (per unit)
Note: This drug pricing data is preliminary, incomplete, and may contain errors.
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
| Organization | Org Type | FDA approvals | Clinical Trials involvement | Org ID | Force Sort |
|---|
Breast Neoplasms (approved 1977)
Carcinoma, Intraductal, Noninfiltrating (approved 1977)
Adenoma (Phase 2)
Adrenocortical Carcinoma (Phase 2)
Aging (Phase 3)
Amyotrophic Lateral Sclerosis (Phase 2)
Arthralgia (Phase 2)
Barrett Esophagus (Early Phase 1)
Bipolar Disorder (Phase 3)
Bone Density (Phase 3)
Brain Neoplasms (Phase 2)
Breast Carcinoma In Situ (Phase 2/Phase 3)
Breast Density (Phase 1/Phase 2)
Breast Diseases (Phase 4)
Breast Neoplasms (Phase 4)
Breast Neoplasms, Male (Phase 3)
Carcinoma in Situ (Phase 3)
Carcinoma, Intraductal, Noninfiltrating (Phase 3)
Cardiotoxicity (Phase 3)
Cardiovascular Diseases (Phase 3)
Cognition (Phase 3)
Colonic Neoplasms (Phase 3)
Colorectal Neoplasms (Phase 3)
Coronary Disease (Phase 3)
COVID-19 (Phase 2)
Cyclophosphamide (Phase 3)
DNA (Phase 1/Phase 2)
Doxorubicin (Phase 3)
Drug Therapy (Phase 2/Phase 3)
Endometrial Neoplasms (Phase 3)
Endometrium (Phase 4)
Erectile Dysfunction (Phase 2)
Esophageal Neoplasms (Phase 2)
Estrogen Receptor Antagonists (Phase 2)
Estrogens (Phase 2)
Fallopian Tube Neoplasms (Phase 3)
Familial Primary Pulmonary Hypertension (Phase 2)
Fatigue (Phase 3)
Fibroadenoma (Phase 4)
Fibrocystic Breast Disease (Phase 4)
Flushing (Phase 2)
Gastrointestinal Neoplasms (Phase 1)
Glioblastoma (Phase 2)
Glioma (Phase 2)
Gynecology (Phase 2)
Hamartoma (Phase 3)
Head and Neck Neoplasms (Phase 2)
Healthy Volunteers (Phase 1)
Heart Diseases (Phase 3)
Hemorrhage (Phase 2)
Hepatitis C, Chronic (Phase 1)
HIV (Phase 2)
HIV Infections (Early Phase 1)
Hormone Antagonists (Phase 2)
Hormones (Phase 3)
Hot Flashes (Phase 2)
Hyperplasia (Phase 3)
Hypertension (Phase 3)
Infertility (Phase 4)
Infertility, Male (Phase 2)
Inflammatory Breast Neoplasms (Phase 3)
Intrauterine Devices, Medicated (Phase 4)
Liver Neoplasms (Phase 3)
Lower Urinary Tract Symptoms (Phase 2)
Lung Diseases (Phase 2)
Lung Neoplasms (Phase 3)
Lymph Nodes (Phase 3)
Mammography (Phase 2)
Mania (Phase 2)
Mastectomy (Phase 2)
Mastodynia (Phase 4)
Melanoma (Phase 2)
Meningitis (Phase 2)
Meningoencephalitis (Phase 2)
Menorrhagia (Phase 4)
Menstruation Disturbances (Phase 4)
Mesothelioma, Malignant (Phase 2)
Metrorrhagia (Phase 4)
mTOR Associated Protein, LST8 Homolog (Phase 1/Phase 2)
Muscular Dystrophy, Duchenne (Phase 3)
Mutation (Phase 2)
Myocardial Ischemia (Phase 3)
Myopathies, Structural, Congenital (Phase 1/Phase 2)
Neoplasm Metastasis (Phase 3)
Neoplasm Recurrence, Local (Phase 3)
Neoplasms ()
Neuroendocrine Tumors (Phase 2)
Oligospermia (Phase 2)
Osteosarcoma (Phase 1)
Ovarian Neoplasms (Phase 3)
Pain (Phase 2/Phase 3)
Pharmacokinetics (Phase 4)
Pheochromocytoma (Phase 2)
Polycystic Ovary Syndrome (Phase 4)
Postmenopause (Phase 4)
Prostatic Neoplasms (Phase 3)
Prostheses and Implants (Phase 2)
Psychotic Disorders (Phase 2)
Pulmonary Arterial Hypertension (Phase 2)
Pulmonary Fibrosis (Phase 3)
Quality of Life (Phase 3)
Retroperitoneal Fibrosis (Phase 2)
Risk Reduction Behavior (Phase 2)
Sarcoma (Phase 2)
Sexuality (Phase 4)
Sleep Wake Disorders (Phase 3)
Stomach Neoplasms (Phase 3)
Tamoxifen (Phase 2)
Telangiectasia, Hereditary Hemorrhagic (Phase 2)
TOR Serine-Threonine Kinases (Phase 2)
Urinary Bladder Neoplasms (Phase 2)
Uterine Cervical Neoplasms (Phase 2)
Uterine Hemorrhage (Phase 4)
Uterine Neoplasms (Phase 2)
Vulvar Diseases (Phase 1/Phase 2)
| Trial | Phase | Start Date | Organizations | Indications |
|---|
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