Identification

Name
Tamoxifen
Accession Number
DB00675  (APRD00123)
Type
Small Molecule
Groups
Approved
Description

One of the selective estrogen receptor modulators (SERM) with tissue-specific activities for the treatment and prevention of estrogen receptor positive breast cancer. 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.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Tamoxifen citrate7FRV7310N654965-24-1FQZYTYWMLGAPFJ-OQKDUQJOSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NolvadexTablet20 mg/1OralAstra Zeneca Lp1994-03-312008-03-31Us
NolvadexTablet10 mg/1OralAstra Zeneca Lp1990-09-012008-03-31Us
Nolvadex Tab 10mgTablet10 mgOralAstra Zeneca1994-12-312003-04-01Canada
Nolvadex-D Tab 20mgTablet20 mgOralAstra Zeneca1995-12-31Not applicableCanada
SoltamoxLiquid10 mg/5mLOralRosemont Pharmaceuticals Ltd2012-10-01Not applicableUs
SoltamoxLiquid20 mg/10mLOralMidatech Pharma Us Inc.2005-10-29Not applicableUs
Tamofen 10Tablet10 mgOralSanofi Aventis1986-12-312011-01-11Canada
Tamofen 20Tablet20 mgOralSanofi Aventis1986-12-312011-01-14Canada
Tamone - (10 Mg)Tablet10 mgOralPfizer1996-12-312007-10-02Canada
Tamone - (20 Mg)Tablet20 mgOralPfizer1996-12-312007-10-02Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-tamox Tab 10mgTablet10 mgOralApotex Corporation1989-12-31Not applicableCanada
Apo-tamox Tab 20mgTablet20 mgOralApotex Corporation1989-12-31Not applicableCanada
Dom-tamoxifenTablet20 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-tamoxifenTablet10 mgOralDominion PharmacalNot applicable2016-10-25Canada
Mylan-tamoxifenTablet10 mgOralMylan Pharmaceuticals1994-12-312017-01-09Canada
Mylan-tamoxifenTablet20 mgOralMylan Pharmaceuticals1994-12-312017-01-09Canada
Penta-tamoxifen TabletsTablet20 mgOralPentapharm Ltd.Not applicableNot applicableCanada
Penta-tamoxifen TabletsTablet10 mgOralPentapharm Ltd.Not applicableNot applicableCanada
PMS-tamoxifenTablet20 mgOralPharmascience Inc1998-12-012016-10-28Canada
PMS-tamoxifenTablet10 mgOralPharmascience Inc1998-12-012016-10-28Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuvyaTamoxifen citrate (0.1 g/0.1g) + Adapalene (0.15 g/0.15g) + Diclofenac sodium (1 g/1g)KitAccumix Pharmaceuticals2014-12-152015-07-17Us
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 (AstraZeneca) / 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
Categories
UNII
094ZI81Y45
CAS number
10540-29-1
Weight
Average: 371.5146
Monoisotopic: 371.224914555
Chemical Formula
C26H29NO
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

Pharmacology

Indication

Tamoxifen is indicated for the treatment of metastatic breast cancer in women and men and ductal carcinoma in Situ.

Associated Conditions
Associated Therapies
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 is a nonsteroidal agent that 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.

TargetActionsOrganism
AEstrogen receptor alpha
antagonist
agonist
Human
AEstrogen receptor beta
antagonist
agonist
Human
U3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
inhibitor
Human
UProtein kinase C
inhibitor
Human
UAndrogen receptorNot AvailableHuman
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
UEstrogen-related receptor gammaNot AvailableHuman
USex hormone-binding globulinNot AvailableHuman
Absorption

When a single oral dose of 20 mg is given, the average peak plasma concentration (Cmax) is 40 ng/mL which occurred approximately 5 hours after dosing (Tmax). The Cmax of N-desmethyl tamoxifen is 15 ng/mL. Steady-state concentrations for tamoxifen is achieved in 4 weeks, while steady-state concentrations for N-desmethyl tamoxifen is achieved in 8 weeks.

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's 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. It is also metabolized by flavin monooxygenases FMO1 and FMO3 to form tamoxifen-N-oxide.

Route of elimination

65% of the dose was excreted from the body over 2 weeks in which fecal excretion was the primary route of elimination. Tamoxifen is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.

Half life

The decline in tamoxifen plasma concentrations is biphasic with a terminal elimination half-life of approximately 5 to 7 days. The estimated half-life of N-desmethyl tamoxifen is 14 days.

Clearance

Clearance (CL/F) as body weight adjusted in female pediatric patients was approximately 2.3-fold higher than in female breast cancer patients.

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
PathwayCategory
Tamoxifen Action PathwayDrug action
Tamoxifen Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A Allele, homozygoteEffect Directly StudiedPatients 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 alleleADR Directly StudiedPatients with this genotype have increased risk of a thromboembolic event with tamoxifen.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor response to drug treatment, shorter time to relapseDetails

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Tamoxifen is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Tamoxifen is combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Tamoxifen.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Tamoxifen is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Tamoxifen.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Tamoxifen.
6-Deoxyerythronolide BThe metabolism of Tamoxifen can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Tamoxifen.
AbciximabThe risk or severity of bleeding can be increased when Tamoxifen is combined with Abciximab.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Tamoxifen.
Food Interactions
Not Available

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
  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:16402113]
  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:8242225]
  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:15639680]
  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:15845599]
  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:16418409]
External Links
Human Metabolome Database
HMDB0014813
KEGG Drug
D08559
KEGG Compound
C07108
PubChem Compound
2733526
PubChem Substance
46505515
ChemSpider
2015313
BindingDB
20607
ChEBI
41774
ChEMBL
CHEMBL83
Therapeutic Targets Database
DAP000108
PharmGKB
PA451581
IUPHAR
1016
Guide to Pharmacology
GtP Drug Page
HET
CTX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tamoxifen
ATC Codes
L02BA01 — Tamoxifen
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1ya4
FDA label
Download (102 KB)
MSDS
Download (74.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
0TerminatedPreventionBarrett's Metaplasia1
1Active Not RecruitingBasic ScienceTumors, Solid1
1Active Not RecruitingTreatmentBreast Cancer - Female / Breast Cancer - Male / Cancer, Breast1
1Active Not RecruitingTreatmentDuchenne's Muscular Dystrophy (DMD)1
1Active Not RecruitingTreatmentHormone Receptor Positive, HER2-negative, Advanced Breast Cancer1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentCancer of the Ovary1
1CompletedTreatmentCancer, Breast4
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentNeoplasms Metastasis / Sarcoma, Osteogenic1
1Not Yet RecruitingBasic ScienceMalignancies / Neoplasms, Gastrointestinal1
1Not Yet RecruitingTreatmentAnatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Anatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v8 / Prognostic Stage IV Breast Cancer AJCC v8 / Recurrent Breast Carcinoma1
1RecruitingOtherCancer, Breast1
1RecruitingTreatmentCancer, Breast / Carcinoma, Breast / Malignant Neoplasm of Breast1
1RecruitingTreatmentNeoplasms, Breast1
1Unknown StatusTreatmentCancer, Breast1
1, 2RecruitingTreatmentCancer of the Ovary / Cancer of the Uterus / Cancer, Breast1
1, 2RecruitingTreatmentNeoplasms, Breast1
1, 2TerminatedTreatmentCancer, Breast / Neoplasms, Breast / Tumors, Breast1
1, 2Unknown StatusTreatmentALS Functional Ration Scale / Amyotrophic Lateral Sclerosis (ALS) / MTOR / Tamoxifen / TAR-DNA-binding Protein-431
2Active Not RecruitingBasic ScienceCancer, Breast1
2Active Not RecruitingPreventionCancer, Breast1
2Active Not RecruitingTreatmentAdvanced, Persistent, or Recurrent Endometrial Cancer1
2Active Not RecruitingTreatmentCancer, Breast4
2Active Not RecruitingTreatmentDesmoid Tumors1
2Active Not RecruitingTreatmentErectile Dysfunction (ED) / Lower Urinary Tract Symptoms (LUTS) / Prostate Cancer1
2Active Not RecruitingTreatmentEstrogen Receptor Positive Breast Cancer1
2Active Not RecruitingTreatmentEstrogen Receptor Positive / HER2/Neu Negative / Recurrent Breast Carcinoma / Stage III Breast Cancer / Stage III Breast Cancer AJCC V7 / Stage IIIA Breast Cancer / Stage IIIA Breast Cancer AJCC v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
2Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2Active Not RecruitingTreatmentNeoplasms, Breast1
2Active Not RecruitingTreatmentMTor Protein / Neoplasms, Breast1
2CompletedNot AvailableAmyotrophic Lateral Sclerosis (ALS)1
2CompletedPreventionCancer, Breast2
2CompletedPreventionCancer, Breast / Hereditary Breast/Ovarian Cancer (brca1, brca2)1
2CompletedSupportive CareCancer, Breast / Menopausal Hot Flushes1
2CompletedTreatmentAdrenocortical Carcinoma / Brain and Central Nervous System Tumors / Head and Neck Carcinoma / Liver Cancer / Mesothelioma, Malignant / Pheochromocytomas / Sarcomas1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentBipolar Disorder (BD)1
2CompletedTreatmentBipolar Disorder (BD) / Mania / Schizoaffective Disorders1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentBrain and Central Nervous System Tumors / Metastatic Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentCancer of the Fallopian Tube / Cancer of the Ovary / Malignant Peritoneal Neoplasm1
2CompletedTreatmentCancer, Breast14
2CompletedTreatmentCancer, Breast / Neoplasms, Breast2
2CompletedTreatmentDuctal Breast Carcinoma In Situ / Estrogen Receptor-Positive Breast Cancer1
2CompletedTreatmentEndometrial Carcinoma / Recurrent Uterine Corpus Carcinoma / Stage IIIA Uterine Corpus Cancer / Stage IIIB Uterine Corpus Cancer / Stage IIIC1 Uterine Corpus Cancer / Stage IIIC2 Uterine Corpus Cancer / Stage IVA Uterine Corpus Cancer / Stage IVB Uterine Corpus Cancer1
2CompletedTreatmentEstrogen Receptor Positive / Male Breast Carcinoma / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentEstrogen Receptor-negative Breast Cancer / Estrogen Receptor-Positive Breast Cancer / Her2-Positive Breast Cancer / Progesterone Receptor-negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer1
2CompletedTreatmentEstrogen Receptor-negative Breast Cancer / Estrogen Receptor-Positive Breast Cancer / Inflammatory carcinoma of the breast / Male Breast Cancer / Progesterone Receptor-negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGliomas1
2CompletedTreatmentGynaecomastia / Prostate Cancer1
2CompletedTreatmentHereditary Haemorrhagic Telangiectasia (HHT)1
2CompletedTreatmentMale Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer1
2CompletedTreatmentMetastatic Breast Cancer (MBC)2
2CompletedTreatmentNeoplasms, Breast3
2CompletedTreatmentNewly Diagnosed Hormone Positive Clinical Stage 1 or 2 Breast Cancer1
2CompletedTreatmentUrinary Bladder Neoplasms1
2Enrolling by InvitationPreventionMammographic Density Reduction / Risk Reduction1
2Not Yet RecruitingOtherCancer, Breast1
2Not Yet RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Metastatic Breast Carcinoma / Metastatic Malignant Neoplasm in the Bone / Progesterone Receptor Positive / Prognostic Stage IV Breast Cancer AJCC v81
2Not Yet RecruitingTreatmentCancer, Breast1
2RecruitingBasic ScienceCancer, Breast1
2RecruitingScreeningNon Metastatic Breast Cancer1
2RecruitingTreatmentBladder Cancers2
2RecruitingTreatmentBreakthrough Bleeding / Haemorrhage / Implants1
2RecruitingTreatmentBreast Cancer Invasive Nos / Cancer, Breast1
2RecruitingTreatmentBreast Cancer Metastatic1
2RecruitingTreatmentBreast Fibroadenoma1
2RecruitingTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast1
2RecruitingTreatmentCancer, Breast3
2RecruitingTreatmentChronic Lung Diseases / Estrogen Receptor Antagonist / Estrogens / Familial Primary Pulmonary Hypertension / High Blood Pressure (Hypertension) / Hormone Antagonists / Primary Pulmonary Hypertension / Pulmonary Arterial Hypertension (PAH) / Tamoxifen1
2RecruitingTreatmentDuctal Breast Carcinoma In Situ / Estrogen Receptor Positive1
2RecruitingTreatmentEarly-Stage Breast Carcinoma / Estrogen Receptor Positive Tumor1
2RecruitingTreatmentEarly-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2RecruitingTreatmentEstrogen Receptor Positive Breast Cancer / Hormone Receptor Positive Malignant Neoplasm of Breast / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast / Metastatic Breast Cancer (MBC) / Progesterone Receptor Positive Tumor1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Meningitis / Meningitis streptococcal / Meningoencephalitis1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentNeoplasms, Breast3
2RecruitingTreatmentOvarian Carcinoma1
2RecruitingTreatmentUterine Cervical Neoplasms1
2TerminatedBasic ScienceBreast Cancer Invasive Nos / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage III Breast Cancer1
2TerminatedTreatmentBiochemical-recurrent Only Epithelial Ovarian Cancer / Cancer of the Ovary / Fallopian Tube Cancer / GU (Genitourinary) Tumors / Primary Peritoneal Carcinoma1
2TerminatedTreatmentCancer, Breast2
2TerminatedTreatmentCancer, Breast / Metastatic Disease1
2TerminatedTreatmentCarcinoma, Breast1
2TerminatedTreatmentMetastatic Breast Cancer (MBC) / One to five years postmenopausal1
2TerminatedTreatmentNeoplasms, Breast1
2Unknown StatusDiagnosticCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2Unknown StatusPreventionCancer, Breast1
2Unknown StatusTreatmentBrain and Central Nervous System Tumors2
2Unknown StatusTreatmentCancer, Breast3
2Unknown StatusTreatmentIntraocular Melanoma1
2Unknown StatusTreatmentMelanoma (Skin)1
2Unknown StatusTreatmentRetroperitoneal Fibrosis1
2WithdrawnTreatmentBreast Cancer Stage II / Breast Cancer Stage III / Cancer, Breast1
2, 3Active Not RecruitingTreatmentLow Grade Ovarian Serous Adenocarcinoma / Micropapillary Serous Carcinoma / Ovarian Serous Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2, 3Not Yet RecruitingPreventionDiscomfort / Pain NOS1
2, 3Not Yet RecruitingTreatmentCancer treatment / Cancer, Breast / Endocrine Breast Diseases1
2, 3TerminatedTreatmentCancer, Breast1
3Active Not RecruitingPreventionCancer, Breast1
3Active Not RecruitingPreventionIntraepithelial Carcinoma1
3Active Not RecruitingTreatmentAdvanced Metastatic Breast Cancer / Advanced, Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBreast Adenocarcinoma / Estrogen Receptor and/or Progesterone Receptor Positive / HER2/Neu Negative / Stage IA Breast Cancer / Stage IA Breast Cancer AJCC v7 / Stage IB Breast Cancer / Stage IB Breast Cancer AJCC v7 / Stage IIA Breast Cancer / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer / Stage IIB Breast Cancer AJCC v6 and v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v71
3Active Not RecruitingTreatmentBreast Adenocarcinoma / HER2 Positive Breast Carcinoma / Stage IA Breast Cancer / Stage IA Breast Cancer AJCC v7 / Stage IB Breast Cancer / Stage IB Breast Cancer AJCC v7 / Stage IIA Breast Cancer / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer / Stage IIB Breast Cancer AJCC v6 and v7 / Stage IIIA Breast Cancer / Stage IIIA Breast Cancer AJCC v71
3Active Not RecruitingTreatmentCancer, Breast6
3Active Not RecruitingTreatmentCancer, Breast / Estrogen Receptor Positive Breast Cancer / Progesterone Receptor Positive Tumor / Recurrent Breast Carcinoma / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer1
3Active Not RecruitingTreatmentDuctal Breast Carcinoma In Situ / Estrogen Receptor and/or Progesterone Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Multicentric Breast Carcinoma / Multifocal Breast Carcinoma / Synchronous Bilateral Breast Carcinoma1
3Active Not RecruitingTreatmentEstrogen Receptor Positive / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
3CompletedNot AvailableBone Density1
3CompletedNot AvailableCancer, Breast1
3CompletedNot AvailableCancer, Breast / Sleep disorders and disturbances / Tiredness1
3CompletedNot AvailableQuality of Life1
3CompletedPreventionAging / Cognition1
3CompletedPreventionCancer, Breast2
3CompletedPreventionCancer, Breast / Endometrial Cancers1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Blood Pressure (Hypertension) / Myocardial Ischemia1
3CompletedPreventionProstate Cancer1
3CompletedTreatmentBipolar Disorder (BD)1
3CompletedTreatmentCancer of the Fallopian Tube / Cancer of the Ovary / Malignant Peritoneal Neoplasm1
3CompletedTreatmentCancer, Breast34
3CompletedTreatmentCancer, Breast / Cyclophosphamide / Doxorubicin / High Risk / Positive Nodes1
3CompletedTreatmentCancer, Breast / Metastasis1
3CompletedTreatmentEarly-Stage Breast Cancer2
3CompletedTreatmentFallopian Tube Cancer / Primary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer / Stage III Ovarian Epithelial Cancer / Stage IV Ovarian Epithelial Cancer1
3CompletedTreatmentHormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women1
3CompletedTreatmentLiver Cancer1
3CompletedTreatmentMale Breast Cancer1
3CompletedTreatmentNeoplasms, Breast4
3Enrolling by InvitationTreatmentCYP2D6 Polymorphism1
3Not Yet RecruitingTreatmentOvarian Carcinoma / Signal Transduction Pathway Deregulation / Therapy-Associated Cancer1
3RecruitingTreatmentCancer, Breast6
3RecruitingTreatmentDuchenne's Muscular Dystrophy (DMD)1
3RecruitingTreatmentInfertilities1
3RecruitingTreatmentMalignant Neoplasm of Female Breast1
3RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3RecruitingTreatmentNeoplasms, Breast1
3TerminatedTreatmentCancer, Breast3
3TerminatedTreatmentCardiac Toxicity / Inflammatory carcinoma of the breast / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
3TerminatedTreatmentEndometrial Cancers1
3Unknown StatusTreatmentCancer, Breast12
3Unknown StatusTreatmentCancer, Breast / Pulmonary Fibrosis1
3WithdrawnTreatmentRecurrent Breast Cancer / Stage IV Breast Cancer1
4CompletedNot AvailableCancer, Breast1
4CompletedBasic SciencePharmacokinetics1
4CompletedHealth Services ResearchCancer, Breast1
4CompletedPreventionHypermenorrhea / Medicated Intrauterine Devices / Metrorrhagia1
4CompletedSupportive CarePolycystic Ovarian Syndrome1
4CompletedTreatmentBenign Breast Disease / Fibroadenoma / Fibrocystic Disease of Breast / Mastodynia1
4CompletedTreatmentCancer, Breast2
4CompletedTreatmentHormono-depending Adjuvant Breast Cancer1
4CompletedTreatmentMenstruation Disturbances1
4Not Yet RecruitingTreatmentEndometrium1
4Not Yet RecruitingTreatmentHER2/Neu Negative / Invasive Breast Carcinoma / One to five years postmenopausal / Stage 0 Breast Cancer / Stage IA Breast Cancer1
4Not Yet RecruitingTreatmentInfertilities1
4RecruitingTreatmentCancer, Breast2
4RecruitingTreatmentSexuality1
Not AvailableActive Not RecruitingNot AvailableCancer, Breast / Depression / Menopausal Hot Flushes / Psychosocial Effects of Cancer and Its Treatment1
Not AvailableActive Not RecruitingHealth Services ResearchCancer, Breast1
Not AvailableCompletedNot AvailableAntineoplastic Agents / Neoplasms, Breast / Survival Analysis / Therapeutic Uses1
Not AvailableCompletedNot AvailableArthralgia/joint pain / BMI >30 kg/m2 / Cancer, Breast1
Not AvailableCompletedNot AvailableCancer, Breast1
Not AvailableCompletedDiagnosticCancer, Breast / CYP2D6 Polymorphism1
Not AvailableCompletedPreventionCancer, Breast / Hodgkins Disease (HD)1
Not AvailableCompletedTreatmentCancer, Breast2
Not AvailableCompletedTreatmentDuctal Breast Carcinoma In Situ / Lobular Breast Carcinoma In Situ / Stage II Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer1
Not AvailableCompletedTreatmentEndometrium / Estrogens / Lipemia / Mammography / Ultrasonography1
Not AvailableCompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Breast Cancer (MBC) / Sarcomas / Tumors, Solid1
Not AvailableEnrolling by InvitationBasic ScienceHigh Background Uptake on MBI1
Not AvailableNot Yet RecruitingNot AvailableCancer, Breast2
Not AvailableNot Yet RecruitingNot AvailableRecurrent Endometrial Cancer / Stage III Endometrial Cancer / Stage IV Endometrial Cancer1
Not AvailableRecruitingTreatmentBreast Cancer Nos Premenopausal1
Not AvailableRecruitingTreatmentCancer, Breast1
Not AvailableTerminatedNot AvailableCancer, Breast2
Not AvailableUnknown StatusNot AvailableCYP2D6 / Genotyping / Neoplasms, Breast / Tamoxifen1
Not AvailableUnknown StatusTreatmentCancer, Breast1
Not AvailableUnknown StatusTreatmentCancer, Breast / Menopausal Symptoms1
Not AvailableUnknown StatusTreatmentInfertilities1

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
FormRouteStrength
TabletOral10 mg
TabletOral20 mg
Kit
LiquidOral10 mg/5mL
LiquidOral20 mg/10mL
TabletOral10 mg/1
TabletOral20 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral20 mg/1
Prices
Unit descriptionCostUnit
Tamoxifen citrate powder50.03USD g
Nolvadex 20 mg tablet4.46USD tablet
Tamoxifen Citrate 20 mg tablet3.94USD tablet
Tamoxifen 20 mg tablet3.79USD tablet
Nolvadex 10 mg tablet2.04USD tablet
Tamoxifen Citrate 10 mg tablet1.97USD tablet
Tamoxifen 10 mg tablet1.89USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6127425No1998-06-262018-06-26Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)97 °CPhysProp
water solubility0.000167 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP7.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00102 mg/mLALOGPS
logP5.93ALOGPS
logP6.35ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity128.43 m3·mol-1ChemAxon
Polarizability44.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.997
Blood Brain Barrier+0.5838
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7718
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IINon-inhibitor0.6225
Renal organic cation transporterInhibitor0.6715
CYP450 2C9 substrateNon-substrate0.8071
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateInhibitor0.8535
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorInhibitor0.8448
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5054
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6058
BiodegradationNot ready biodegradable0.9048
Rat acute toxicity1.9882 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7402
hERG inhibition (predictor II)Inhibitor0.6898
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-3972000000-38c8a6cb6c6f2505438b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9006000000-8443975759913521d9cd

Taxonomy

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
Stilbene / Diphenylmethane / Phenylpropane / Phenoxy compound / Phenol ether / Alkyl aryl ether / Benzenoid / Monocyclic benzene moiety / Tertiary aliphatic amine / Tertiary amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, stilbenoid (CHEBI:41774)

Targets

Details
1. Estrogen receptor alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Zinc ion binding
Specific 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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:2011412]
  3. Fabian CJ, Kimler BF: Chemoprevention for high-risk women: tamoxifen and beyond. Breast J. 2001 Sep-Oct;7(5):311-20. [PubMed:11906441]
  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. doi: 10.1002/cmdc.201000146. [PubMed:20512796]
Details
2. Estrogen receptor beta
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Zinc ion binding
Specific Function
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 m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:16010412]
  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:16326830]
  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:16822624]
  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:17158759]
  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:17404078]
  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:2011412]
  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 Nov;88(5):626-9. doi: 10.1038/clpt.2010.143. Epub 2010 Sep 8. [PubMed:20827267]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane signaling receptor activity
Specific Function
Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
Gene Name
EBP
Uniprot ID
Q15125
Uniprot Name
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
Molecular Weight
26352.615 Da
References
  1. 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. [PubMed:9618436]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differenti...

Components:
References
  1. O'Brian CA, Liskamp RM, Solomon DH, Weinstein IB: Inhibition of protein kinase C by tamoxifen. Cancer Res. 1985 Jun;45(6):2462-5. [PubMed:3157445]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. 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. [PubMed:14751673]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. 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. [PubMed:15272206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific 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 an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [PubMed:16054614]
  2. 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. [PubMed:18839173]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response ...
Gene Name
ESRRG
Uniprot ID
P62508
Uniprot Name
Estrogen-related receptor gamma
Molecular Weight
51305.485 Da
References
  1. 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. [PubMed:16889744]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific 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...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. 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. [PubMed:25349334]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. 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. [PubMed:20425602]
  2. Kuderer NM, Peppercorn J: CYP2D6 testing in breast cancer: ready for prime time? Oncology (Williston Park). 2009 Dec;23(14):1223-32. [PubMed:20120834]
  3. Goetz MP: Tamoxifen, endoxifen, and CYP2D6: the rules for evaluating a predictive factor. Oncology (Williston Park). 2009 Dec;23(14):1233-4, 1236. [PubMed:20120835]
  4. 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:15159443]
  5. 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:12124303]
  6. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Details
2. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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:15159443]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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:12124305]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. 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. [PubMed:17024799]
  2. 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. [PubMed:25091503]
  3. Tamoxifen FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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:15159443]
  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:12124303]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Details
7. Cytochrome P450 2B6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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:15159443]
  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:12124303]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. 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. [PubMed:27709010]
  5. 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. [PubMed:17101742]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. 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:12124303]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. 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:12124303]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
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.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. 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. [PubMed:16684653]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
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 impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
References
  1. 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. [PubMed:16684653]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
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:15601807]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Triglyceride lipase activity
Specific Function
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 acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
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:16081098]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific 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. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. 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. [PubMed:17664247]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estroge...
Gene Name
SULT1A1
Uniprot ID
P50225
Uniprot Name
Sulfotransferase 1A1
Molecular Weight
34165.13 Da
References
  1. 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. [PubMed:17244352]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
Curator comments
Induces MDR1 expression but inhibits transporter action.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:10825468]
  2. 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:15386482]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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:12668685]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. 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. [PubMed:20124171]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:50