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Identification
Name Tamoxifen
Accession Number DB00675 (APRD00123)
Type small molecule
Groups approved
Description

One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Tamoxifen Citrate
  • Tamoxifene [INN-French]
  • Tamoxifeno [INN-Spanish]
  • Tamoxifenum [INN-Latin]
  • Trans-Tamoxifen
Brand names
  • Apo-Tamox
  • Citofen
  • Crisafeno
  • Diemon
  • Gen-Tamoxifen (Genpharm)
  • Istubol
  • Kessar
  • Noltam
  • Nolvadex (AstraZeneca)
  • Nolvadex-D (AstraZeneca)
  • Nourytam
  • Novo-Tamoxifen (Novopharm)
  • Oncomox
  • PMS-Tamoxifen (Pharmascience)
  • Retaxim
  • Tamizam
  • Tamofen (Sanofi-Aventis)
  • Tamone
  • Tamoxasta
  • Tamoxen
  • Valodex
  • Zemide
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents, Hormonal
  • Selective Estrogen Receptor Modulators
  • Estrogen Antagonists
  • Bone Density Conservation Agents
CAS number 10540-29-1
Weight Average: 371.5146
Monoisotopic: 371.224914555
Chemical Formula C26H29NO
InChI Key InChIKey=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-
Plain Text
IUPAC Name
(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
SMILES
CC\C(C1=CC=CC=C1)=C(/C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Stilbenes
Substructures
  • Stilbenes
  • Alkanes and Alkenes
  • Phenols and Derivatives
  • Phenylpropenes
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Aromatic compounds
  • Anisoles
  • Styrene Derivatives
  • Phenyl Esters
Pharmacology
Indication For the treatment of breast cancer.
Pharmacodynamics Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity.
Mechanism of action Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic. Tamoxifen is extensively metabolized after oral administration. N-Desmethyl-tamoxifen is the major metabolite found in plasma. N-Desmethyl-tamoxifen activity is similar to tamoxifen. 4-hydroxy-tamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. 4-Hydroxy-tamoxifen formation is catalyzed mainly by cytochrome P450 (CYP) 2D6, and also by CYP2C9 and 3A4. At high tamoxifen concentrations, CYP2B6 also catalyzes 4-hydroxylation of the parent drug. 4-Hydroxy-tamoxifen possesses 30- to 100-times greater affinity for the estrogen receptor and 30- to 100-times greater potency at inhibiting estrogen-dependent cell proliferation compared to tamoxifen.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 1B1 4-Hydroxy-tamoxifen 4-hydroxytamoxifen cis-trans isomerization
Cytochrome P450 3A5 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 3A5 4-Hydroxy-tamoxifen oxidation
Cytochrome P450 3A5 3-Hydroxy-tamoxifen oxidation
Cytochrome P450 2D6 4-Hydroxy-tamoxifen oxidation
Cytochrome P450 2D6 4-Hydroxy-N-desmethyl-tamoxifen (endoxifen) oxidation of N-desmethyltamoxifen
Cytochrome P450 2D6 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 1A2 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 3A4 N-Desmethyl-tamoxifen N-demethylation 50 174.38
Cytochrome P450 3A4 4-Hydroxy-tamoxifen oxidation
Cytochrome P450 3A4 3-Hydroxy-tamoxifen oxidation
Cytochrome P450 3A4 α-Hydroxy-N-desmethyl-tamoxifen oxidation of N-desmethyl-tamoxifen
Cytochrome P450 3A4 N-Didesmethyl-tamoxifen demethylation of N-desmethyl-tamoxifen
Cytochrome P450 3A4 3,4-Dihydroxy-tamoxifen oxidation of 4-hydroxy-tamoxifen
Cytochrome P450 3A4 4-Hydroxy-N-desmethyl-tamoxifen (endoxifen) demethylation of 4-hydroxy-tamoxifen
Cytochrome P450 2C9 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 2C9 4-Hydroxy-tamoxifen oxidation
Cytochrome P450 2C19 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 2C19 4-Hydroxy-tamoxifen oxidation, 4-hydroxytamoxifen cis-trans isomerization
Cytochrome P450 1A1 N-Desmethyl-tamoxifen N-demethylation
Cytochrome P450 2B6 4-Hydroxy-tamoxifen oxidation, 4-hydroxytamoxifen cis-trans isomerization
Cytochrome P450 2B6 3-Hydroxy-tamoxifen oxidation
Dimethylaniline monooxygenase [N-oxide-forming] 3 Tamoxifen N-oxide oxidation
Dimethylaniline monooxygenase [N-oxide-forming] 1 Tamoxifen N-oxide oxidation
Route of elimination The drug is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
Half life Distribution t1/2=7 to 14 hours; Elimination t1/2=5 to 7 days; Elimination t1/2 of N-desmethyl-tamoxifen=9-14 days.
Clearance Not Available
Toxicity Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00471 Tamoxifen Pathway SMP00471
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
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 20 mg
Prices
Unit description Cost Unit
Tamoxifen citrate powder 50.03 USD g
Nolvadex 20 mg tablet 4.46 USD tablet
Tamoxifen Citrate 20 mg tablet 3.94 USD tablet
Tamoxifen 20 mg tablet 3.79 USD tablet
Nolvadex 10 mg tablet 2.04 USD tablet
Tamoxifen Citrate 10 mg tablet 1.97 USD tablet
Tamoxifen 10 mg tablet 1.89 USD tablet
Patents
Country Patent Number Approved Expires
United States 6127425 1998-06-26 2018-06-26
Properties
State solid
Melting point 97 oC
Experimental Properties
Property Value Source
water solubility 0.000167 mg/mL at 25 oC [MEYLAN,WM et al. (1996)] PhysProp
logP 7.1 PhysProp
Predicted Properties
Property Value Source
water solubility 1.02e-03 g/l ALOGPS
logP 5.93 ALOGPS
logP 6.35 ChemAxon Molconvert
logS -5.56 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 12.47 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 128.43 ChemAxon Molconvert
polarizability 44.19 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Jordan VC: Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol. 2006 Jan;147 Suppl 1:S269-76. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. Steiner AZ, Terplan M, Paulson RJ: Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005 Jun;20(6):1511-5. Epub 2005 Apr 21. Pubmed
  5. van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG: Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis. Ann Intern Med. 2006 Jan 17;144(2):101-6. Pubmed
External Links
Resource Link
KEGG Drug D00966 Link_out
KEGG Compound C07108 Link_out
PubChem Compound 2733526 Link_out
PubChem Substance 46505515 Link_out
ChemSpider 2015313 Link_out
BindingDB 20607 Link_out
ChEBI 9396 Link_out
ChEMBL 9396 Link_out
Therapeutic Targets Database DAP000108 Link_out
PharmGKB PA451581 Link_out
HET OHT Link_out
Drug Product Database 2237460 Link_out
RxList http://www.rxlist.com/cgi/generic/tamox.htm Link_out
Drugs.com http://www.drugs.com/tamoxifen.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tamoxifen Link_out
ATC Codes
  • L02BA01
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (101.6 KB)
MSDS show (74.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Estrogen receptor

Pharmacological action: yes
Actions: antagonist, agonist

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

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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. Pubmed
  3. Fabian CJ, Kimler BF: Chemoprevention for high-risk women: tamoxifen and beyond. Breast J. 2001 Sep-Oct;7(5):311-20. Pubmed
  4. 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. Pubmed

2. Estrogen receptor beta

Pharmacological action: yes
Actions: antagonist, agonist

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual

Organism class: human
UniProt ID: Q92731 Link_out
Gene: ESR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. 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. Pubmed
  7. 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. Pubmed
  8. 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 Sep 8. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Higgins MJ, Stearns V: CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Kuderer NM, Peppercorn J: CYP2D6 testing in breast cancer: ready for prime time? Oncology (Williston Park). 2009 Dec;23(14):1223-32. Pubmed, Link.
  5. Goetz MP: Tamoxifen, endoxifen, and CYP2D6: the rules for evaluating a predictive factor. Oncology (Williston Park). 2009 Dec;23(14):1233-4, 1236. Pubmed, Link.
  6. 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. Pubmed
  7. 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. Pubmed
  8. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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. Pubmed

3. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2B6

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Pubmed

10. Cytochrome P450 1B1

Actions: substrate, inhibitor

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

11. Dimethylaniline monooxygenase [N-oxide-forming] 1

Actions: substrate

This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines

UniProt ID: Q01740 Link_out
Gene: FMO1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

12. Dimethylaniline monooxygenase [N-oxide-forming] 3

Actions: substrate

Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds

UniProt ID: P31513 Link_out
Gene: FMO3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

13. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

14. Liver carboxylesterase 1

Actions: inhibitor

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl CoA ester

UniProt ID: P23141 Link_out
Gene: CES1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed

15. Cytochrome P450 19A1

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

16. Cytochrome P450 2A6

Actions: substrate

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

17. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  3. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. Pubmed
  4. 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. Pubmed
  5. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  6. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed

2. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed

3. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 11, 2010 12:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.