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PubChem
| Name: | Tamoxifen |
|---|---|
| PubChem Compound ID: | 11451630 |
| Description: | One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM. |
| Molecular formula: | C26H29NO |
| Molecular weight: | 374.533 g/mol |
DrugBank
Identification
| Name: | Tamoxifen |
|---|---|
| Name (isomeric): | DB00675 |
| Drug Type: | small molecule |
| Description: | One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM. |
| Synonyms: |
Tamoxifen Citrate; Tamoxifenum [INN-Latin]; Tamoxifeno [INN-Spanish]; Trans-Tamoxifen; Tamoxifene [INN-French]
|
| Brand: | Nolvadex-D, Tamone, Crisafeno, Diemon, Novo-Tamoxifen, Zemide, Tamizam, Nourytam, PMS-Tamoxifen, Noltam, Apo-Tamox, Gen-Tamoxifen, Nolvadex, Tamofen, Retaxim, Tamoxasta, Citofen, Tamoxen, Valodex, Istubol, Oncomox, Kessar |
| Category: | Estrogen Antagonists, Antineoplastic Agents, Hormonal, Bone Density Conservation Agents, Selective Estrogen Receptor Modulators |
| CAS number: | 10540-29-1 |
Pharmacology
| Indication: | For the treatment of breast cancer. |
|---|---|
| Pharmacology: | Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity. |
| Mechanism of Action: |
Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptak...
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Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. 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.
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| Biotransformation: | Hepatic. Tamoxifen is extensively metabolized after oral administration. N-Desmethyl-tamoxifen is the major metabolite found in plasma. N-Desmethyl-tamoxifen activity is similar to tamoxifen. 4-hydroxy-tamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. 4-Hydroxy-tamoxifen formation is catalyzed mainly by cytochrome P450 (CYP) 2D6, and also by CYP2C9 and 3A4. At high tamoxifen concentrations, CYP2B6 also catalyzes 4-hydroxylation of the parent drug. 4-Hydroxy-tamoxifen possesses 30- to 100-times greater affinity for the estrogen receptor and 30- to 100-times greater potency at inhibiting estrogen-dependent cell proliferation compared to tamoxifen. |
| Route of elimination: | The drug is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity. |
| Half Life: | Distribution t1/2=7 to 14 hours; Elimination t1/2=5 to 7 days; Elimination t1/2 of N-desmethyl-tamoxifen=9-14 days. |
| Toxicity: | Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions. |
| Affected organisms: | Humans and other mammals |
Interactions
| Drug interaction: |
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Targets
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues
| UniProt ID: | P03372 | ||||
|---|---|---|---|---|---|
| Gene: | ESR1 | ||||
| Actions: | antagonist, agonist | ||||
| References: |
|
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual
| UniProt ID: | Q92731 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | ESR2 | ||||||||
| Actions: | antagonist, agonist | ||||||||
| References: |
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Enzymes
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
| UniProt ID: | P10635 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | CYP2D6 | ||||||||
| Actions: | substrate, inhibitor | ||||||||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide
| UniProt ID: | P08684 | |||||
|---|---|---|---|---|---|---|
| Gene: | CYP3A4 | |||||
| Actions: | substrate, inhibitor, inducer | |||||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P20815 | |||
|---|---|---|---|---|
| Gene: | CYP3A5 | |||
| Actions: | substrate | |||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P24462 | |
|---|---|---|
| Gene: | CYP3A7 | |
| Actions: | substrate | |
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan
| UniProt ID: | P11712 | |||
|---|---|---|---|---|
| Gene: | CYP2C9 | |||
| Actions: | substrate, inhibitor | |||
| References: |
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Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine
| UniProt ID: | P33261 | ||||
|---|---|---|---|---|---|
| Gene: | CYP2C19 | ||||
| Actions: | substrate | ||||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P20813 | ||||
|---|---|---|---|---|---|
| Gene: | CYP2B6 | ||||
| Actions: | substrate, inhibitor | ||||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
| UniProt ID: | P04798 | |||
|---|---|---|---|---|
| Gene: | CYP1A1 | |||
| Actions: | substrate | |||
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen
| UniProt ID: | P05177 | ||
|---|---|---|---|
| Gene: | CYP1A2 | ||
| Actions: | substrate | ||
| References: |
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Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development
| UniProt ID: | Q16678 | |||
|---|---|---|---|---|
| Gene: | CYP1B1 | |||
| Actions: | substrate, inhibitor | |||
| References: |
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This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines
| UniProt ID: | Q01740 | |
|---|---|---|
| Gene: | FMO1 | |
| Actions: | substrate | |
| References: |
|
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds
| UniProt ID: | P31513 | |
|---|---|---|
| Gene: | FMO3 | |
| Actions: | substrate | |
| References: |
|
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)
| UniProt ID: | P10632 | ||
|---|---|---|---|
| Gene: | CYP2C8 | ||
| Actions: | inhibitor | ||
| References: |
|
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl CoA ester
| UniProt ID: | P23141 | |
|---|---|---|
| Gene: | CES1 | |
| Actions: | inhibitor | |
| References: |
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Catalyzes the formation of aromatic C18 estrogens from C19 androgens
| UniProt ID: | P11511 | |
|---|---|---|
| Gene: | CYP19A1 | |
| Actions: | inhibitor | |
| References: |
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Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase
| UniProt ID: | P11509 | |
|---|---|---|
| Gene: | CYP2A6 | |
| Actions: | substrate | |
| References: |
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Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms
| UniProt ID: | P05181 | |
|---|---|---|
| Gene: | CYP2E1 | |
| Actions: | substrate | |
| References: |
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Transporters
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
| UniProt ID: | P08183 | ||||||
|---|---|---|---|---|---|---|---|
| Gene: | ABCB1 | ||||||
| Actions: | substrate, inhibitor, inducer | ||||||
| References: |
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Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
| UniProt ID: | Q9UNQ0 | |
|---|---|---|
| Gene: | ABCG2 | |
| Actions: | substrate | |
| References: |
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Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
| UniProt ID: | O95342 | |
|---|---|---|
| Gene: | ABCB11 | |
| Actions: | inhibitor | |
| References: |
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