Tamoxifen
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Identification
- Summary
Tamoxifen is a selective estrogen receptor modulator used to treat estrogen receptor positive breast cancer, reduce the risk of invasive breast cancer following surgery, or reduce the risk of breast cancer in high risk women.
- Brand Names
- Soltamox
- Generic Name
- Tamoxifen
- DrugBank Accession Number
- DB00675
- Background
Tamoxifen is a non-steroidal antiestrogen used to treat estrogen receptor positive breast cancers as well as prevent the incidence of breast cancer in high risk populations.1,15,16 Tamoxifen is used alone or as an adjuvant in these treatments.15,16 Tamoxifen may no longer be the preferred treatment for these types of cancers as patients generally have better survival, side effect profiles, and compliance with anastrozole.2
Tamoxifen was granted FDA approval on 30 December 1977.15
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 371.5146
Monoisotopic: 371.224914555 - Chemical Formula
- C26H29NO
- Synonyms
- (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine
- (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine
- 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene
- 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene
- Tamoxifen
- Tamoxifène
- Tamoxifene
- Tamoxifeno
- Tamoxifenum
- trans-Tamoxifen
- External IDs
- ICI 47699
- ICI-47699
Pharmacology
- Indication
Tamoxifen is indicated to treat estrogen receptor positive metastatic breast cancer in adults, as an adjuvant in the treatment of early stage estrogen receptor positive breast cancer in adults, to reduce the risk of invasive breast cancer after surgery and radiation in adult women with ductal carcinoma in situ.16
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Breast cancer •••••••••••• ••••• •••• •••• ••••••• ••••••••• •••••• Adjunct therapy in prevention of Contralateral breast cancer •••••••••••• ••••• ••••••• ••••••••• •••••• Used in combination to treat Desmoid tumour Regimen in combination with: Sulindac (DB00605) ••• ••••• Adjunct therapy in treatment of Early stage estrogen receptor (er) positive breast cancer •••••••••••• ••••• ••••••• ••••••••• •••••• Treatment of Gynecomastia ••• ••••• - Associated Therapies
- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Tamoxifen is a selective estrogen receptor modulator that inhibits growth and promotes apoptosis in estrogen receptor positive tumors.1,8 It has a long duration of action as the active metabolite N-desmethyltamoxifen has a half life of approximately 2 weeks.15,16 It has a narrow therapeutic index as higher doses can lead to breathing difficulty or convulsions.15,16 Tamoxifen administration is also associated with an increased incidence of uterine malignancies.15,16
- Mechanism of action
Tamoxifen competitively inhibits estrogen binding to its receptor, which is critical for it's activity in breast cancer cells.1 Tamoxifen leads to a decrease in tumor growth factor α and insulin-like growth factor 1, and an increase in sex hormone binding globulin.1 The increase in sex hormon binding globulin limits the amount of freely available estradiol.1 These changes reduce levels of factors that stimulate tumor growth.1
Tamoxifen has also been shown to induce apoptosis in estrogen receptor positive cells.8 This action is thought to be the result of inhibition of protein kinase C, which prevents DNA synthesis.8 Alternate theories for the apoptotic effect of tamoxifen comes from the approximately 3 fold increase in intracellular and mitochondrial calcium ion levels after administration or the induction of tumor growth factor β.8
Target Actions Organism AEstrogen receptor antagonistagonistHumans AEstrogen receptor beta antagonistagonistHumans AProtein kinase C inhibitorHumans ASex hormone-binding globulin inducerHumans U3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase inhibitorHumans UAndrogen receptor Not Available Humans UVoltage-gated inwardly rectifying potassium channel KCNH2 inhibitorHumans UNuclear receptor subfamily 1 group I member 2 Not Available Humans UEstrogen-related receptor gamma Not Available Humans UMitogen-activated protein kinase 8 modulatorHumans - Absorption
An oral dose of 20mg reaches a Cmax of 40ng/mL with a Tmax of 5 hours.15,16 The metabolite N-desmethyltamoxifen reaches a Cmax of 15ng/mL.15,16 10mg of tamoxifen orally twice daily for 3 months results in a Css of 120ng/mL and a Css of 336ng/mL.15,16
- Volume of distribution
The volume of distribution of tamoxifen is approximately 50-60L/kg.11
- Protein binding
The protein binding of tamoxifen in plasma is over 98% and mostly to serum albumin.11
- Metabolism
Tamoxifen can by hydroxylated to α-hydroxytamoxifen which is then glucuronidated or undergoes sulfate conjugation by sulfotransferase 2A1.4,6 Tamoxifen can also undergo N-oxidation by flavin monooxygenases 1 and 3 to tamoxifen N-oxide.4,6,7 Tamoxifen is N-dealkylated to N-desmethyltamoxifen by CYP2D6, CYP1A1, CYP1A2, CYP3A4, CYP1B1, CYP2C9, CYP2C19, and CYP3A5.3,4,5,6,7 N-desmethyltamoxifen can be sulfate conjugated to form N-desmethyltamoxifen sulfate, 4-hydroxylated by CYP2D6 to form endoxifen, or N-dealkylated again by CYP3A4 and CYP3A5 to N,N-didesmethyltamoxifen.4,5,13 N,N-didesmethyltamoxifen undergoes a substitution reaction to form tamoxifen metabolite Y, followed by ether cleavage to metabolite E, which can then be sulfate conjugated by sulfotransferase 1A1 and 1E1 or O-glucuronidated.13,14
Tamoxifen can also by 4-hydroxylated by CYP2D6, CYP2B6, CYP3A4, CYP2C9, and CYP2C19 to form 4-hydroxytamoxifen.3,4,5,6 4-hydroxytamoxifen can undergo glucuronidation by UGT1A8, UGT1A10, UGT2B7, and UGT2B17 to tamoxifen glucuronides, sulfate conjugation by sulfotransferase 1A1 and 1E1 to 4-hydroxytamoxifen sulfate, or N-dealkylation by CYP3A4 and CYP3A5 to endoxifen.4,5
Endoxifen undergoes demethylation to norendoxifen, a reversible sulfate conjugation reaction via sulfotransferase 1A1 and 1E1 to 4-hydroxytamoxifen sulfate, sulfate conjugation via sulfotransferase 2A1 to 4-endoxifen sulfate, or glucuronidation via UGT1A8, UGT1A10, UGT2B7, or UGT2B15 to tamoxifen glucuronides.13,4,5
Hover over products below to view reaction partners
- Route of elimination
Tamoxifen is mainly eliminated in the feces.15,16 Animal studies have shown 75% of radiolabelled tamoxifen recovered in the feces, with negligible collection from urine.9 However, 1 human study showed 26.7% recovery in the urine and 24.7% in the feces.10
- Half-life
The terminal elimination half-life of tamoxifen is 5 to 7 days, while the half-life of N-desmethyltamoxifen, the primary circulating metabolite, is approximately 14 days.15,16
- Clearance
The clearance of tamoxifen was 189mL/min in a study of six postmenopausal women.12
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
High doses of tamoxifen in animals lead to respiratory difficulty and convulsions.15,16 High doses in advanced metastatic cancer patients resulted in acute neurotoxicity seen by tremor, hyperreflexia, unsteady gait, and dizziness.15,16 Patients experiencing and overdose should be given supportive treatment as no specific treatment for overdose is suggested.15,16
- Pathways
Pathway Category Tamoxifen Metabolism Pathway Drug metabolism Tamoxifen Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*4 (A;A) A Allele, homozygote Effect Directly Studied Patients with this genotype have reduced metabolism of tamoxifen resulting in reduced plasma concentrations its active form endoxifen. Details Coagulation factor V --- (A;A) / (A;G) A allele ADR Directly Studied Patients with this genotype have increased risk of a thromboembolic event with tamoxifen. Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor response to drug treatment, shorter time to relapse Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Tamoxifen can be increased when it is combined with Abametapir. Abatacept The metabolism of Tamoxifen can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Tamoxifen is combined with Abciximab. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Tamoxifen. Abiraterone The metabolism of Tamoxifen can be decreased when combined with Abiraterone. - Food Interactions
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of tamoxifen.
- Take with a full glass of water.
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Tamoxifen citrate 7FRV7310N6 54965-24-1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N - Product Images
- International/Other Brands
- Adifen (Medicamerc) / Adopan (Sawai Seiyaku) / Bilem (Teva Int'l) / Caditam (Cadila) / Citofen / Crisafeno (LKM) / Doctamoxifene (Docpharma) / Ebefen (Ebewe) / Fenahex (Sandoz) / Genox (Merck Serono) / Gynatam (Biogalenic) / Istubal (AstraZeneca) / Mammonex (CP Pharmaceuticals) / Neophedan (Aspen Pharmacare) / Noltam / Nolvadex-D (AstraZeneca) / Novofen (Remedica) / Oncomox (Sun) / Tadex (Orion) / Tamifen (Medochemie) / Tamizam (Mithra) / Tamofen (Sanofi-Aventis) / Tamoneprin (Actavis) / Tamoplex (Pharmachemie) / Tamoxen (Ascent) / Tamoxilon (Celon) / Tamtero (Hetero) / Tecnotax (Zodiac) / Tomifen (Alkem) / Valodex / Zemide
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nolvadex Tablet 20 mg/1 Oral Astrazeneca Ab 1994-03-31 2008-03-31 US Nolvadex Tablet 10 mg/1 Oral Astrazeneca Ab 1990-09-01 2008-03-31 US Nolvadex Tab 10mg Tablet 10 mg Oral Astrazeneca Ab 1994-12-31 2003-04-01 Canada Nolvadex-D Tab 20mg Tablet 20 mg Oral Astrazeneca Ab 1995-12-31 2023-03-22 Canada Soltamox Liquid 20 mg/10mL Oral Fortovia Therapeutics, Inc. 2005-10-29 2022-06-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-tamox Tab 10mg Tablet 10 mg Oral Apotex Corporation 1989-12-31 Not applicable Canada Apo-tamox Tab 20mg Tablet 20 mg Oral Apotex Corporation 1989-12-31 Not applicable Canada Dom-tamoxifen Tablet 10 mg / tab Oral Dominion Pharmacal Not applicable 2016-10-25 Canada Dom-tamoxifen Tablet 20 mg / tab Oral Dominion Pharmacal Not applicable Not applicable Canada Mylan-tamoxifen Tablet 10 mg Oral Mylan Pharmaceuticals Inc. 1994-12-31 2017-01-09 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Nuvya Tamoxifen citrate (0.1 g/0.1g) + Adapalene (0.15 g/0.15g) + Diclofenac sodium (1 g/1g) Kit Topical Accumix Pharmaceuticals 2014-12-15 2015-07-17 US
Categories
- ATC Codes
- L02BA01 — Tamoxifen
- Drug Categories
- Anti-Estrogens
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Benzene Derivatives
- Benzylidene Compounds
- BSEP/ABCB11 Inhibitors
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP2A6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (moderate)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Endocrine Therapy
- Estrogen Agonist/Antagonist
- Estrogen Antagonists
- Estrogen Receptor Modulators
- Hormone Antagonists
- Hormone Antagonists and Related Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Narrow Therapeutic Index Drugs
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Selective Estrogen Receptor Modulators
- Stilbenes
- Thyroxine-binding globulin inducers
- UGT2B17 substrates
- UGT2B7 substrates
- UGT2B7 Substrates with a Narrow Therapeutic Index
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Stilbenes
- Sub Class
- Not Available
- Direct Parent
- Stilbenes
- Alternative Parents
- Diphenylmethanes / Phenylpropanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Benzenoid / Diphenylmethane / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxygen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- tertiary amino compound, stilbenoid (CHEBI:41774)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 094ZI81Y45
- CAS number
- 10540-29-1
- InChI Key
- NKANXQFJJICGDU-QPLCGJKRSA-N
- InChI
- 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-
- IUPAC Name
- (2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
- SMILES
- CC\C(=C(/C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1
References
- Synthesis Reference
Chengjian Mao, "Tamoxifen and 4-hydroxytamoxifen-activated system for regulated production of proteins in eukaryotic cells." U.S. Patent US20030199022, issued October 23, 2003.
US20030199022- General References
- Jordan VC: Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol. 1993 Oct;110(2):507-17. [Article]
- Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [Article]
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Squirewell EJ, Qin X, Duffel MW: Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50. doi: 10.1124/dmd.114.059709. Epub 2014 Aug 25. [Article]
- Cronin-Fenton DP, Damkier P, Lash TL: Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168. [Article]
- White IN: The tamoxifen dilemma. Carcinogenesis. 1999 Jul;20(7):1153-60. doi: 10.1093/carcin/20.7.1153. [Article]
- Parte P, Kupfer D: Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3 to tamoxifen-N-oxide and its novel reduction back to tamoxifen by human cytochromes P450 and hemoglobin. Drug Metab Dispos. 2005 Oct;33(10):1446-52. doi: 10.1124/dmd.104.000802. Epub 2005 Jun 29. [Article]
- Radin DP, Patel P: Delineating the molecular mechanisms of tamoxifen's oncolytic actions in estrogen receptor-negative cancers. Eur J Pharmacol. 2016 Jun 15;781:173-80. doi: 10.1016/j.ejphar.2016.04.017. Epub 2016 Apr 12. [Article]
- Fromson JM, Pearson S, Bramah S: The metabolism of tamoxifen (I.C.I. 46,474). I. In laboratory animals. Xenobiotica. 1973 Nov;3(11):693-709. doi: 10.3109/00498257309151594. [Article]
- Kisanga ER, Mellgren G, Lien EA: Excretion of hydroxylated metabolites of tamoxifen in human bile and urine. Anticancer Res. 2005 Nov-Dec;25(6C):4487-92. [Article]
- Lien EA, Solheim E, Lea OA, Lundgren S, Kvinnsland S, Ueland PM: Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res. 1989 Apr 15;49(8):2175-83. [Article]
- Lien EA, Anker G, Lonning PE, Solheim E, Ueland PM: Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res. 1990 Sep 15;50(18):5851-7. [Article]
- Klein DJ, Thorn CF, Desta Z, Flockhart DA, Altman RB, Klein TE: PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics. 2013 Nov;23(11):643-7. doi: 10.1097/FPC.0b013e3283656bc1. [Article]
- Kemp JV, Adam HK, Wakeling AE, Slater R: Identification and biological activity of tamoxifen metabolites in human serum. Biochem Pharmacol. 1983 Jul 1;32(13):2045-52. doi: 10.1016/0006-2952(83)90425-2. [Article]
- FDA Approved Drug Products: Tamoxifen Oral Tablets [Link]
- FDA Approved Drug Products: Tamoxifen Oral Solution [Link]
- External Links
- Human Metabolome Database
- HMDB0014813
- KEGG Drug
- D08559
- KEGG Compound
- C07108
- PubChem Compound
- 2733526
- PubChem Substance
- 46505515
- ChemSpider
- 2015313
- BindingDB
- 20607
- 10324
- ChEBI
- 41774
- ChEMBL
- CHEMBL83
- ZINC
- ZINC000001530689
- Therapeutic Targets Database
- DAP000108
- PharmGKB
- PA451581
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- CTX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tamoxifen
- PDB Entries
- 1ya4 / 6ohu / 6sxf
- FDA label
- Download (102 KB)
- MSDS
- Download (74.8 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Antineoplastic Agents / Breast Neoplasms / Survival Analysis / Therapeutic Uses 1 somestatus stop reason just information to hide Not Available Completed Not Available Breast Cancer 2 somestatus stop reason just information to hide Not Available Completed Not Available Breast Cancer / Depression / Hot Flashes / Psychosocial Effects of Cancer and Its Treatment 1 somestatus stop reason just information to hide Not Available Completed Not Available Breast Cancer / Joint Pain / Obesity 1 somestatus stop reason just information to hide Not Available Completed Not Available HR+ HER2- Men, Pre/Postmenopausal Advanced Breast Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Rosemont group ltd
- Astrazeneca pharmaceuticals lp
- Aegis pharmaceuticals inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Mylan pharmaceuticals inc
- Pharmachemie bv
- Roxane laboratories inc
- Teva pharmaceuticals usa inc
- Teva pharmaceuticals usa
- Watson laboratories inc
- Watson laboratories inc florida
- Packagers
- Amerisource Health Services Corp.
- AQ Pharmaceuticals Inc.
- AstraZeneca Inc.
- Barr Pharmaceuticals
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Egis Pharmaceuticals Public Ltd. Co.
- Imperial Chemical Industrial Ltd.
- Innovative Manufacturing and Distribution Services Inc.
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Mckesson Corp.
- Medisca Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Pharmedix
- Physicians Total Care Inc.
- Ranbaxy Laboratories
- Resource Optimization and Innovation LLC
- Roxane Labs
- Southwood Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- Wampole Laboratories
- Watson Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 10.000 mg Tablet, film coated Oral Tablet, coated Oral 20 mg Tablet, coated Oral 10 MG Kit Topical Liquid Oral 10 mg/5mL Liquid Oral 20 mg/10mL Tablet Oral 10 mg Tablet, film coated Oral 30.4 MG Tablet Oral 10 mg / tab Tablet Oral 20 mg / tab Tablet, film coated Oral 30.34 mg Tablet, film coated Oral 10 MG Tablet Oral 30.34 mg Tablet, film coated Oral 20 mg Tablet, film coated Oral 30 MG Tablet, film coated Oral 40 MG Tablet Oral 30 MG Tablet Oral 10 mg/1 Tablet Oral 20 mg/1 Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 20 mg/1 Tablet Oral 20 mg Tablet Oral 20.000 mg Tablet Oral 15.1714 mg - Prices
Unit description Cost Unit Tamoxifen citrate powder 50.03USD g Nolvadex 20 mg tablet 4.46USD tablet Tamoxifen Citrate 20 mg tablet 3.94USD tablet Tamoxifen 20 mg tablet 3.79USD tablet Nolvadex 10 mg tablet 2.04USD tablet Tamoxifen Citrate 10 mg tablet 1.97USD tablet Tamoxifen 10 mg tablet 1.89USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6127425 No 2000-10-03 2018-06-26 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 97 °C http://www.chemspider.com/Chemical-Structure.2015313.html?rid=1b2fa2ba-dc6c-450e-bcf7-467741bd4eb1 - Predicted Properties
Property Value Source Water Solubility 0.00102 mg/mL ALOGPS logP 5.93 ALOGPS logP 6.35 Chemaxon logS -5.6 ALOGPS pKa (Strongest Basic) 8.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 128.43 m3·mol-1 Chemaxon Polarizability 44.19 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.997 Blood Brain Barrier + 0.5838 Caco-2 permeable + 0.8866 P-glycoprotein substrate Substrate 0.7718 P-glycoprotein inhibitor I Inhibitor 0.8564 P-glycoprotein inhibitor II Non-inhibitor 0.6225 Renal organic cation transporter Inhibitor 0.6715 CYP450 2C9 substrate Non-substrate 0.8071 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.7407 CYP450 1A2 substrate Inhibitor 0.8535 CYP450 2C9 inhibitor Non-inhibitor 0.9072 CYP450 2D6 inhibitor Inhibitor 0.8448 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5054 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.6058 Biodegradation Not ready biodegradable 0.9048 Rat acute toxicity 1.9882 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.7402 hERG inhibition (predictor II) Inhibitor 0.6898
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 209.8623073 predictedDarkChem Lite v0.1.0 [M-H]- 205.3501951 predictedDarkChem Lite v0.1.0 [M-H]- 206.1413073 predictedDarkChem Lite v0.1.0 [M-H]- 207.2886073 predictedDarkChem Lite v0.1.0 [M-H]- 193.0686 predictedDeepCCS 1.0 (2019) [M+H]+ 210.0216073 predictedDarkChem Lite v0.1.0 [M+H]+ 198.8827 predictedDarkChem Lite v0.1.0 [M+H]+ 206.0743073 predictedDarkChem Lite v0.1.0 [M+H]+ 207.4181073 predictedDarkChem Lite v0.1.0 [M+H]+ 195.42662 predictedDeepCCS 1.0 (2019) [M+Na]+ 209.6959073 predictedDarkChem Lite v0.1.0 [M+Na]+ 201.9844656 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.8263073 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.0269073 predictedDarkChem Lite v0.1.0 [M+Na]+ 202.25468 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- 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. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
- Specific Function
- 14-3-3 protein binding
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. [Article]
- Fabian CJ, Kimler BF: Chemoprevention for high-risk women: tamoxifen and beyond. Breast J. 2001 Sep-Oct;7(5):311-20. [Article]
- Cyrus K, Wehenkel M, Choi EY, Lee H, Swanson H, Kim KB: Jostling for position: optimizing linker location in the design of estrogen receptor-targeting PROTACs. ChemMedChem. 2010 Jul 5;5(7):979-85. doi: 10.1002/cmdc.201000146. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)
- Specific Function
- DNA binding
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Chen B, Gajdos C, Dardes R, Kidwai N, Johnston SR, Dowsett M, Jordan VC: Potential of endogenous estrogen receptor beta to influence the selective ER modulator ERbeta complex. Int J Oncol. 2005 Aug;27(2):327-35. [Article]
- Horner-Glister E, Maleki-Dizaji M, Guerin CJ, Johnson SM, Styles J, White IN: Influence of oestradiol and tamoxifen on oestrogen receptors-alpha and -beta protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells. J Mol Endocrinol. 2005 Dec;35(3):421-32. [Article]
- Girault I, Bieche I, Lidereau R: Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer. Maturitas. 2006 Jul 20;54(4):342-51. Epub 2006 Jul 5. [Article]
- Mc Ilroy M, Fleming FJ, Buggy Y, Hill AD, Young LS: Tamoxifen-induced ER-alpha-SRC-3 interaction in HER2 positive human breast cancer; a possible mechanism for ER isoform specific recurrence. Endocr Relat Cancer. 2006 Dec;13(4):1135-45. [Article]
- Gruvberger-Saal SK, Bendahl PO, Saal LH, Laakso M, Hegardt C, Eden P, Peterson C, Malmstrom P, Isola J, Borg A, Ferno M: Estrogen receptor beta expression is associated with tamoxifen response in ERalpha-negative breast carcinoma. Clin Cancer Res. 2007 Apr 1;13(7):1987-94. [Article]
- Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. [Article]
- Hayes DF, Skaar TC, Rae JM, Henry NL, Nguyen AT, Stearns V, Li L, Philips S, Desta Z, Flockhart DA: Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results. Clin Pharmacol Ther. 2010 Nov;88(5):626-9. doi: 10.1038/clpt.2010.143. Epub 2010 Sep 8. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231)
- Specific Function
- ATP binding
Components:
References
- O'Brian CA, Liskamp RM, Solomon DH, Weinstein IB: Inhibition of protein kinase C by tamoxifen. Cancer Res. 1985 Jun;45(6):2462-5. [Article]
- Radin DP, Patel P: Delineating the molecular mechanisms of tamoxifen's oncolytic actions in estrogen receptor-negative cancers. Eur J Pharmacol. 2016 Jun 15;781:173-80. doi: 10.1016/j.ejphar.2016.04.017. Epub 2016 Apr 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
- Specific Function
- androgen binding
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
- Radin DP, Patel P: Delineating the molecular mechanisms of tamoxifen's oncolytic actions in estrogen receptor-negative cancers. Eur J Pharmacol. 2016 Jun 15;781:173-80. doi: 10.1016/j.ejphar.2016.04.017. Epub 2016 Apr 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers
- Specific Function
- C-8 sterol isomerase activity
- Gene Name
- EBP
- Uniprot ID
- Q15125
- Uniprot Name
- 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
- Molecular Weight
- 26352.615 Da
References
- Paul R, Silve S, De Nys N, Dupuy PH, Bouteiller CL, Rosenfeld J, Ferrara P, Le Fur G, Casellas P, Loison G: Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. J Pharmacol Exp Ther. 1998 Jun;285(3):1296-302. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3
- Specific Function
- androgen binding
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 99187.115 Da
References
- Yamasaki K, Sawaki M, Noda S, Muroi T, Takakura S, Mitoma H, Sakamoto S, Nakai M, Yakabe Y: Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals. Toxicology. 2004 Feb 15;195(2-3):177-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
- Specific Function
- delayed rectifier potassium channel activity
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Voltage-gated inwardly rectifying potassium channel KCNH2
- Molecular Weight
- 126653.52 Da
References
- Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
- Specific Function
- DNA-binding transcription activator activity, RNA polymerase II-specific
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [Article]
- Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle
- Specific Function
- AF-2 domain binding
- Gene Name
- ESRRG
- Uniprot ID
- P62508
- Uniprot Name
- Estrogen-related receptor gamma
- Molecular Weight
- 51305.485 Da
References
- Gowda K, Marks BD, Zielinski TK, Ozers MS: Development of a coactivator displacement assay for the orphan receptor estrogen-related receptor-gamma using time-resolved fluorescence resonance energy transfer. Anal Biochem. 2006 Oct 1;357(1):105-15. Epub 2006 Jul 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Modulator
- General Function
- Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572)
- Specific Function
- ATP binding
- Gene Name
- MAPK8
- Uniprot ID
- P45983
- Uniprot Name
- Mitogen-activated protein kinase 8
- Molecular Weight
- 48295.14 Da
References
- Radin DP, Patel P: Delineating the molecular mechanisms of tamoxifen's oncolytic actions in estrogen receptor-negative cancers. Eur J Pharmacol. 2016 Jun 15;781:173-80. doi: 10.1016/j.ejphar.2016.04.017. Epub 2016 Apr 12. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Higgins MJ, Stearns V: CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15. doi: 10.1007/s11912-009-0076-5. [Article]
- Kuderer NM, Peppercorn J: CYP2D6 testing in breast cancer: ready for prime time? Oncology (Williston Park). 2009 Dec;23(14):1223-32. [Article]
- Goetz MP: Tamoxifen, endoxifen, and CYP2D6: the rules for evaluating a predictive factor. Oncology (Williston Park). 2009 Dec;23(14):1233-4, 1236. [Article]
- Desta Z, Ward BA, Soukhova NV, Flockhart DA: Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. Epub 2004 May 24. [Article]
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Desta Z, Ward BA, Soukhova NV, Flockhart DA: Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. Epub 2004 May 24. [Article]
- Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
- Zhao XJ, Jones DR, Wang YH, Grimm SW, Hall SD: Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites. Xenobiotica. 2002 Oct;32(10):863-78. doi: 10.1080/00498250210158230 . [Article]
- Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL: Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279-304. doi: 10.2165/00003088-200544030-00005. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- all-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Boruban MC, Yasar U, Babaoglu MO, Sencan O, Bozkurt A: Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4. doi: 10.1179/joc.2006.18.4.421. [Article]
- Saladores P, Murdter T, Eccles D, Chowbay B, Zgheib NK, Winter S, Ganchev B, Eccles B, Gerty S, Tfayli A, Lim JS, Yap YS, Ng RC, Wong NS, Dent R, Habbal MZ, Schaeffeler E, Eichelbaum M, Schroth W, Schwab M, Brauch H: Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J. 2015 Feb;15(1):84-94. doi: 10.1038/tpj.2014.34. Epub 2014 Aug 5. [Article]
- Tamoxifen FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Desta Z, Ward BA, Soukhova NV, Flockhart DA: Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. Epub 2004 May 24. [Article]
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Desta Z, Ward BA, Soukhova NV, Flockhart DA: Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. Epub 2004 May 24. [Article]
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Hedrich WD, Hassan HE, Wang H: Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425. doi: 10.1016/j.apsb.2016.07.016. Epub 2016 Aug 9. [Article]
- Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)
- Specific Function
- aromatase activity
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Zhao XJ, Jones DR, Wang YH, Grimm SW, Hall SD: Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites. Xenobiotica. 2002 Oct;32(10):863-78. doi: 10.1080/00498250210158230 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad spectrum monooxygenase that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including xenobiotics (PubMed:32156684). Catalyzes the S-oxygenation of hypotaurine to produce taurine, an organic osmolyte involved in cell volume regulation as well as a variety of cytoprotective and developmental processes (PubMed:32156684). In vitro, catalyzes the N-oxygenation of trimethylamine (TMA) to produce trimethylamine N-oxide (TMAO) and could therefore participate to the detoxification of this compound that is generated by the action of gut microbiota from dietary precursors such as choline, choline containing compounds, betaine or L-carnitine (By similarity)
- Specific Function
- flavin adenine dinucleotide binding
- Gene Name
- FMO1
- Uniprot ID
- Q01740
- Uniprot Name
- Flavin-containing monooxygenase 1
- Molecular Weight
- 60310.285 Da
References
- Krueger SK, Vandyke JE, Williams DE, Hines RN: The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev. 2006;38(1-2):139-47. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds (PubMed:10759686, PubMed:30381441, PubMed:32156684). Plays an important role in the metabolism of trimethylamine (TMA), via the production of trimethylamine N-oxide (TMAO) metabolite (PubMed:9776311). TMA is generated by the action of gut microbiota using dietary precursors such as choline, choline containing compounds, betaine or L-carnitine. By regulating TMAO concentration, FMO3 directly impacts both platelet responsiveness and rate of thrombus formation (PubMed:29981269)
- Specific Function
- albendazole monooxygenase activity
- Gene Name
- FMO3
- Uniprot ID
- P31513
- Uniprot Name
- Flavin-containing monooxygenase 3
- Molecular Weight
- 60032.975 Da
References
- Krueger SK, Vandyke JE, Williams DE, Hines RN: The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev. 2006;38(1-2):139-47. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [Article]
- Jernstrom H, Bageman E, Rose C, Jonsson PE, Ingvar C: CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients. Br J Cancer. 2009 Dec 1;101(11):1817-23. doi: 10.1038/sj.bjc.6605428. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
- Specific Function
- carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR: Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil. J Mol Biol. 2005 Sep 9;352(1):165-77. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874)
- Specific Function
- aromatase activity
- Gene Name
- CYP19A1
- Uniprot ID
- P11511
- Uniprot Name
- Aromatase
- Molecular Weight
- 57882.48 Da
References
- Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML: Estrogen synthesis in human colon cancer epithelial cells. J Steroid Biochem Mol Biol. 1999 Dec 31;71(5-6):223-30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- 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. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56517.005 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Styles JA, Davies A, Lim CK, De Matteis F, Stanley LA, White IN, Yuan ZX, Smith LL: Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9. doi: 10.1093/carcin/15.1.5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:18719240, PubMed:23288867, PubMed:26220143). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A10
- Uniprot ID
- Q9HAW8
- Uniprot Name
- UDP-glucuronosyltransferase 1A10
- Molecular Weight
- 59809.075 Da
References
- Sun D, Sharma AK, Dellinger RW, Blevins-Primeau AS, Balliet RM, Chen G, Boyiri T, Amin S, Lazarus P: Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14. Epub 2007 Jul 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine groupe. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Displays broad substrate specificity for small phenolic compounds. Plays an important role in the sulfonation of endogenous molecules such as steroid hormones and 3,3'-diiodothyronin (PubMed:10199779, PubMed:12471039, PubMed:16221673, PubMed:21723874, PubMed:22069470, PubMed:7834621). Mediates the sulfate conjugation of a variety of xenobiotics, including the drugs acetaminophen and minoxidil (By similarity). Mediates also the metabolic activation of carcinogenic N-hydroxyarylamines leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis (PubMed:7834621). May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system
- Specific Function
- 3'-phosphoadenosine 5'-phosphosulfate binding
- Gene Name
- SULT1A1
- Uniprot ID
- P50225
- Uniprot Name
- Sulfotransferase 1A1
- Molecular Weight
- 34165.13 Da
References
- Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S: Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res. 2007;9(1):R7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands. Mediates the sulfation of a wide range of steroids and sterols, including pregnenolone, androsterone, DHEA, bile acids, cholesterol and as well many xenobiotics that contain alcohol and phenol functional groups (PubMed:14573603, PubMed:18042734, PubMed:19589875, PubMed:21187059, PubMed:2268288, PubMed:29671343, PubMed:7678732, PubMed:7854148). Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Plays an important role in maintening steroid and lipid homeostasis (PubMed:14573603, PubMed:19589875, PubMed:21187059). Plays a key role in bile acid metabolism (PubMed:2268288). In addition, catalyzes the metabolic activation of potent carcinogenic polycyclic arylmethanols (By similarity)
- Specific Function
- 3'-phosphoadenosine 5'-phosphosulfate binding
- Gene Name
- SULT2A1
- Uniprot ID
- Q06520
- Uniprot Name
- Sulfotransferase 2A1
- Molecular Weight
- 33779.57 Da
References
- Squirewell EJ, Qin X, Duffel MW: Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50. doi: 10.1124/dmd.114.059709. Epub 2014 Aug 25. [Article]
- White IN: The tamoxifen dilemma. Carcinogenesis. 1999 Jul;20(7):1153-60. doi: 10.1093/carcin/20.7.1153. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM: Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74. [Article]
- Squirewell EJ, Qin X, Duffel MW: Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50. doi: 10.1124/dmd.114.059709. Epub 2014 Aug 25. [Article]
- Cronin-Fenton DP, Damkier P, Lash TL: Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168. [Article]
- White IN: The tamoxifen dilemma. Carcinogenesis. 1999 Jul;20(7):1153-60. doi: 10.1093/carcin/20.7.1153. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- Cronin-Fenton DP, Damkier P, Lash TL: Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:8798464). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol) (PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:8798464)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B17
- Uniprot ID
- O75795
- Uniprot Name
- UDP-glucuronosyltransferase 2B17
- Molecular Weight
- 61094.915 Da
References
- Cronin-Fenton DP, Damkier P, Lash TL: Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone (PubMed:11006110, PubMed:11884392, PubMed:7779757). Is a key enzyme in estrogen homeostasis, the sulfation of estrogens leads to their inactivation. Also sulfates dehydroepiandrosterone (DHEA), pregnenolone, (24S)-hydroxycholesterol and xenobiotic compounds like ethinylestradiol, equalenin, diethyl stilbesterol and 1-naphthol at significantly lower efficiency (PubMed:11006110, PubMed:19589875). Does not sulfonate cortisol, testosterone and dopamine (PubMed:11006110, PubMed:7779757). May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system
- Specific Function
- aryl sulfotransferase activity
- Gene Name
- SULT1E1
- Uniprot ID
- P49888
- Uniprot Name
- Sulfotransferase 1E1
- Molecular Weight
- 35126.185 Da
References
- Cronin-Fenton DP, Damkier P, Lash TL: Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Lien EA, Solheim E, Lea OA, Lundgren S, Kvinnsland S, Ueland PM: Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res. 1989 Apr 15;49(8):2175-83. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- Major thyroid hormone transport protein in serum
- Specific Function
- serine-type endopeptidase inhibitor activity
- Gene Name
- SERPINA7
- Uniprot ID
- P05543
- Uniprot Name
- Thyroxine-binding globulin
- Molecular Weight
- 46324.12 Da
References
- CYTOMEL (liothyronine) FDA label [File]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- Curator comments
- Induces MDR1 expression but inhibits transporter action.
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Riley J, Styles J, Verschoyle RD, Stanley LA, White IN, Gant TW: Association of tamoxifen biliary excretion rate with prior tamoxifen exposure and increased mdr1b expression. Biochem Pharmacol. 2000 Jul 15;60(2):233-9. [Article]
- Bekaii-Saab TS, Perloff MD, Weemhoff JL, Greenblatt DJ, von Moltke LL: Interactions of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen with P-glycoprotein and CYP3A. Biopharm Drug Dispos. 2004 Oct;25(7):283-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW: Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51. Epub 2003 Mar 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Kiyotani K, Mushiroda T, Imamura CK, Hosono N, Tsunoda T, Kubo M, Tanigawara Y, Flockhart DA, Desta Z, Skaar TC, Aki F, Hirata K, Takatsuka Y, Okazaki M, Ohsumi S, Yamakawa T, Sasa M, Nakamura Y, Zembutsu H: Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. J Clin Oncol. 2010 Mar 10;28(8):1287-93. doi: 10.1200/JCO.2009.25.7246. Epub 2010 Feb 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- ABC-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs (PubMed:14754908). Transports preferentially phosphatidylcholine over phosphatidylserine (PubMed:24097981). May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908, PubMed:24097981, PubMed:35974019). Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain (PubMed:35974019)
- Specific Function
- ABC-type transporter activity
- Gene Name
- ABCA1
- Uniprot ID
- O95477
- Uniprot Name
- Phospholipid-transporting ATPase ABCA1
- Molecular Weight
- 254299.89 Da
References
- Klein DJ, Thorn CF, Desta Z, Flockhart DA, Altman RB, Klein TE: PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics. 2013 Nov;23(11):643-7. doi: 10.1097/FPC.0b013e3283656bc1. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:04