TAMOXIFEN PHARMACOKINETICS PATHWAY (PW:0000838)

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Description

Tamoxifen (TAM, TX), an non-steroidal anti-estrogen, is one of the most commonly used drugs for the treatment and prevention of breast cancer. Estrogen is involved in the growth and development of breast cancers; estrogen mediated transcription is constitutively active in more than 50% of cases. Initially considered an antagonist, TAM is currently classified as a selective estrogen receptor modulator (SERM). It binds competitively to the estrogen receptors (ERs) acting as an antagonist in breast

Pathway Diagram:

Ariadne Genomics Inc. CYP3A4 SULT1A1 4-OH-TAM UGTs endoxifen UGTs endoxifen CYPs 4-OH-TAM CYPs DMT CYPs ABCB1 Sult2a1 Cyp3a2 tamoxifen ---> DMT PAPS(2) UDPGA 4-OH-TAM ---> 4-OH-TAM-gluc PAPS(1) ---> alpha-OH-TAM-S tamoxifen ---> alpha-OH-TAM tamoxifen ---> 4-OH-TAM 4-OH-TAM ---> endoxifen UDPGA ---> endoxifen-gluc alpha-OH-TAM ---> alpha-OH-TAM-S alpha-OH-TAM-S ---> DNA adducts endoxifen elimination endoxifen ---> endoxifen elimination PAPS(2) ---> 4-OH-TAM-S UDPGA ---> 4-OH-TAM-gluc endoxifen ---> endoxifen-gluc DMT ---> endoxifen 4-OH-TAM ---> 4-OH-TAM-S 4-OH-TAM-gluc endoxifen-gluc hSULT2A1 DMT alpha-OH-TAM PAPS(1) alpha-OH-TAM-S DNA adducts endoxifen 4-OH-TAM 4-OH-TAM-S tamoxifen
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Genes in Pathway:

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tamoxifen pharmacokinetics pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Cyp2b3 cytochrome P450, family 2, subfamily b, polypeptide 3 JBrowse link 1 83,163,103 83,236,615 RGD:10402751
G Cyp2d4 cytochrome P450, family 2, subfamily d, polypeptide 4 JBrowse link 7 123,599,264 123,608,436 RGD:10402751
G Cyp3a2 cytochrome P450, family 3, subfamily a, polypeptide 2 JBrowse link 12 11,641,500 11,677,818 RGD:5129544
G Cyp3a23/3a1 cytochrome P450, family 3, subfamily a, polypeptide 23/polypeptide 1 JBrowse link 12 11,053,888 11,082,742 RGD:5129544
G Cyp3a9 cytochrome P450, family 3, subfamily a, polypeptide 9 JBrowse link 12 19,074,288 19,114,491 RGD:10402751
G Esr1 estrogen receptor 1 JBrowse link 1 41,192,029 41,594,799 RGD:10402751
G Fmo1 flavin containing monooxygenase 1 JBrowse link 13 80,712,885 80,745,095 RGD:10402751
G Fmo3 flavin containing monooxygenase 3 JBrowse link 13 80,837,418 80,856,214 RGD:10402751
G Sult1a1 sulfotransferase family 1A member 1 JBrowse link 1 198,100,586 198,104,106 RGD:10402751
G Sult2a1 sulfotransferase family 2A member 1 JBrowse link 1 76,558,721 76,614,315 RGD:5129555
G Ugt1a5 UDP glucuronosyltransferase family 1 member A5 JBrowse link 9 95,256,628 95,302,822 RGD:10402751

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Small MoleculePAPS3'-phosphoadenosine-5'-phosphosulfate
Small MoleculeDMTN-desmethyltamoxifen
Gene Groupendoxifen CYPsthe set of human cytochrome P450 enzymes involved in the conversion of DMT and 4-OH-DMT to tamoxifen
Gene Group4-OH-TAM CYPsthe set of human cytochrome P450 enzymes involved in the conversion of tamoxifen to 4-OH-TAM
Gene Group4-OH-TAM UGTsthe set of human UDP-glucuronosyltransferase enzymes involved in the conjugation of 4-OH-TAM metabolites
Gene Groupendoxifen UGTsthe set of human UDP-glucuronosyltransferase enzymes involved in the conjugation of endoxifen metabolites
Gene GroupDMT CYPsthe set of rat and human cytochrome P450 enzymes involved in the conversion of tamoxifen to DMT
Small MoleculeUDPGAuridine diphosphate glucuronic acid

Pathway Gene Annotations

Disease Annotations Associated with Genes in the tamoxifen pharmacokinetics pathway
Disease TermsGene Symbols
Acute Kidney InjuryCyp2d4 , Cyp3a23/3a1
adenocarcinomaEsr1
Adenoma, Liver CellCyp3a23/3a1
Adenomatous Polyposis ColiFmo3
Alzheimer's DiseaseCyp2d4 , Esr1
Amphetamine-Related DisordersCyp2d4
amyotrophic lateral sclerosis type 1Fmo1
Anxiety DisordersCyp3a2
ArteriosclerosisEsr1
Arthritis, ExperimentalEsr1
astrocytomaEsr1
atherosclerosisEsr1
Basal Ganglia DiseasesCyp2d4
benign neoplasmSult1a1
Bone DiseasesEsr1
Bone Diseases, MetabolicEsr1
BradycardiaCyp2d4
breast cancerEsr1 , Sult1a1
breast cancer, familialEsr1
Breast NeoplasmsCyp2d4 , Cyp3a2 , Esr1 , Sult1a1
Bronchial HyperreactivityEsr1
CarcinomaEsr1
Carcinoma in SituEsr1
Carcinoma, HepatocellularEsr1
Cataract, Cortical, Juvenile-OnsetEsr1
Cell Transformation, NeoplasticEsr1
Cerebellar AtaxiaEsr1
Chemical and Drug Induced Liver InjuryCyp2b3 , Cyp3a23/3a1 , Fmo3
Chemotherapy-Induced Febrile NeutropeniaCyp3a9
Chromosome AberrationsSult1a1
chronic myeloid leukemiaCyp3a9
chronic periodontitisEsr1
Cognition DisordersCyp2d4
Colonic NeoplasmsSult1a1
Colorectal NeoplasmsSult1a1
ComaCyp2d4
Coronary Artery DiseaseEsr1
Crigler Najjar Syndrome, Type 2Ugt1a5
Crigler-Najjar SyndromeUgt1a5
CryptorchidismEsr1
diabetes mellitus, experimentalCyp2b3 , Esr1
Diabetic NephropathiesEsr1
Disease Models, AnimalEsr1
Disease ProgressionEsr1
Drug Metabolism, Poor, CYP2D6-RelatedCyp2d4
Drug-induced leukopeniaCyp3a9
Drug-induced NeutropeniaCyp3a9
Drug-Related Side Effects and Adverse ReactionsCyp2b3 , Cyp2d4
Dyskinesia, Drug-InducedCyp2d4
DystoniaCyp2d4
EFAVIRENZ, POOR METABOLISM OFCyp2b3
endometrial cancerSult1a1
Endometrial NeoplasmsEsr1 , Sult1a1
endometrioid carcinomaEsr1
EndometriosisEsr1
Epilepsy, Tonic-ClonicCyp2d4
esophageal squamous cell carcinomaSult1a1
essential hypertensionCyp3a9
Estrogen ResistanceEsr1
familial prostate cancerCyp3a2
Female Urogenital DiseasesEsr1
FeminizationEsr1
Fractures, BoneEsr1
Genomic InstabilitySult1a1
Gilbert DiseaseUgt1a5
GliosarcomaCyp2b3
GlomerulonephritisEsr1
Hepatitis C, ChronicCyp2d4
Hepatitis, AutoimmuneCyp2d4
HyperalgesiaEsr1
HyperbilirubinemiaUgt1a5
Hyperbilirubinemia, Transient Familial NeonatalUgt1a5
HypertensionFmo3
HypotensionSult1a1
Immunologic Deficiency SyndromesCyp3a9
InfertilityEsr1
Infertility, FemaleEsr1
Infertility, MaleEsr1
InflammationCyp3a2 , Cyp3a23/3a1
inherited metabolic disorderFmo3
Kidney DiseasesCyp3a9
Kidney Failure, ChronicCyp2b3 , Cyp3a2
LeiomyomaEsr1
LeukemiaEsr1
Leukemia, Myeloid, AcuteCyp2d4
Leukemia, Myeloid, Chronic-PhaseCyp3a9
Leydig Cell TumorEsr1
Liver Cirrhosis, ExperimentalCyp2d4 , Cyp3a9 , Fmo1 , Sult2a1
Liver NeoplasmsEsr1
lung adenocarcinomaSult1a1
lung cancerSult1a1
Lung NeoplasmsEsr1
lung squamous cell carcinomaSult1a1
lymphangioleiomyomatosisEsr1
Macular DegenerationEsr1
Mammary Neoplasms, AnimalEsr1
Mammary Neoplasms, ExperimentalEsr1
Manganese PoisoningCyp2d4
MelanomaEsr1
mental depressionCyp3a23/3a1
MesotheliomaEsr1
Migraine DisordersEsr1
MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 1Esr1
Multiple MyelomaCyp2d4
Muscle RigidityCyp2d4
Muscular Dystrophy, Emery-DreifussEsr1
Musculoskeletal PainEsr1
Myocardial InfarctionEsr1
Myocardial IschemiaSult1a1
Myocardial Reperfusion InjuryEsr1
Neoplasm InvasivenessEsr1
Neoplasm MetastasisEsr1
Neoplasm Recurrence, LocalEsr1
Nephritis, InterstitialCyp2d4
NephrosisCyp3a9
neuroblastomaEsr1
neurotoxicity syndromesCyp3a9
non-small cell lung carcinomaEsr1
obesityEsr1
Occupational DiseasesCyp2d4
OligospermiaEsr1
OsteoarthritisEsr1
Osteoarthritis, HandEsr1
Osteoarthritis, HipEsr1
Osteoarthritis, KneeEsr1
OsteoporosisEsr1
Osteoporosis, PostmenopausalEsr1
Osteoporotic FracturesEsr1
Ovarian NeoplasmsEsr1 , Sult1a1
Parkinson's DiseaseCyp2d4
Parkinsonian DisordersEsr1
PeritonitisEsr1
Pleomorphic Xanthoastrocytoma Cyp3a9
PleurisyEsr1
Precursor B-Cell Lymphoblastic Leukemia-LymphomaCyp3a9
Precursor Cell Lymphoblastic Leukemia-LymphomaCyp2d4 , Cyp3a9
Prenatal Exposure Delayed EffectsCyp2d4
prostate carcinoma in situEsr1
Prostatic HyperplasiaEsr1
prostatic neoplasmsCyp2d4 , Cyp3a9 , Esr1 , Sult1a1 , Sult2a1
Psychoses, Substance-InducedEsr1
pulmonary hypertensionEsr1
Reperfusion InjuryCyp3a9
SchizophreniaSult1a1
Scleroderma, SystemicEsr1
Sexual Dysfunctions, PsychologicalCyp2d4
Shock, HemorrhagicEsr1
Spinal Cord InjuriesEsr1
Spinal FracturesEsr1
Spinocerebellar Ataxia, Autosomal Recessive 8Esr1
Stomach NeoplasmsSult1a1
Subarachnoid HemorrhageEsr1
Substance-Related DisordersCyp2d4
ThrombosisCyp3a9
Tobacco Addiction, Susceptibility ToCyp2b3
transient cerebral ischemiaEsr1
TremorCyp2d4
TrimethylaminuriaFmo3
type 2 diabetes mellitusCyp3a2 , Cyp3a23/3a1 , Esr1
urinary bladder cancerEsr1 , Sult1a1
Urination DisordersEsr1
Urologic NeoplasmsSult1a1
Varicose UlcerEsr1
VitiligoEsr1
Vulvar Lichen SclerosusEsr1
Weight GainCyp2d4
Pathway Annotations Associated with Genes in the tamoxifen pharmacokinetics pathway
Pathway TermsGene Symbols
acetylsalicylic acid pharmacodynamics pathwayCyp2b3
antipyrine drug pathwayCyp2b3
arachidonic acid metabolic pathwayCyp2b3
artemether pharmacokinetics pathwayCyp3a9
ascorbate and aldarate metabolic pathwayUgt1a5
bile acid transport pathwaySult2a1
bisphenol A response pathwayEsr1
carbamazepine pharmacokinetics pathwayCyp2b3 , Cyp3a9
celecoxib pharmacodynamics pathwayCyp2b3 , Cyp2d4
celecoxib pharmacokinetics pathwayCyp2d4
citalopram pharmacodynamics pathwayCyp2d4
citalopram pharmacokinetics pathwayCyp2d4
clomipramine pharmacokinetics pathwayCyp2d4
clopidogrel pharmacodynamics pathwayCyp2b3 , Cyp3a9
clopidogrel pharmacokinetics pathwayCyp2b3 , Cyp3a9
codeine and morphine pharmacodynamics pathwayCyp2d4
codeine and morphine pharmacokinetics pathwayCyp2d4
cyclophosphamide pharmacodynamics pathwayCyp2b3
cyclophosphamide pharmacokinetics pathwayCyp2b3
desipramine pharmacodynamics pathwayCyp2d4
desipramine pharmacokinetics pathwayCyp2d4
diclofenac pharmacodynamics pathwayCyp2b3
diflunisal pharmacodynamics pathwayCyp2b3
doxepin pharmacokinetics pathwayCyp2d4
estradiol biosynthetic pathwaySult2a1
estrogen signaling pathwayEsr1
etodolac pharmacodynamics pathwayCyp2b3
etoposide pharmacodynamics pathwayCyp3a9
etoposide pharmacokinetics pathwayCyp3a9
fenoprofen pharmacodynamics pathwayCyp2b3
fluoxetine pharmacodynamics pathwayCyp2d4 , Cyp3a9
fluoxetine pharmacokinetics pathwayCyp2d4 , Cyp3a9
flurbiprofen pharmacodynamics pathwayCyp2b3
follicle-stimulating hormone signaling pathwayEsr1
forkhead class A signaling pathwayEsr1
histamine signaling pathway, immunologicalEsr1
ibuprofen pharmacodynamics pathwayCyp2b3
ifosfamide pharmacodynamics pathwayCyp2b3 , Cyp3a9
ifosfamide pharmacokinetics pathwayCyp2b3 , Cyp3a9
imipramine pharmacodynamics pathwayCyp2d4
imipramine pharmacokinetics pathwayCyp2d4
indometacin pharmacodynamics pathwayCyp2b3
indometacin pharmacodynamics pathwayCyp2b3
insulin-like growth factor signaling pathwayEsr1
irinotecan pharmacodynamics pathwayCyp3a9
irinotecan pharmacokinetics pathwayCyp3a9
ketoprofen pharmacodynamics pathwayCyp2b3
ketorolac pharmacodynamics pathwayCyp2b3
lamivudine pharmacokinetics pathwaySult1a1
leukotriene C4 synthase deficiency pathwayCyp2b3
linoleic acid metabolic pathwayCyp3a2 , Cyp3a23/3a1 , Cyp3a9
lornoxicam pharmacodynamics pathwayCyp2b3
luteinizing hormone signaling pathwayEsr1
magnesium salicylate pharmacodynamics pathwayCyp2b3
mefenamic acid pharmacodynamics pathwayCyp2b3
meloxicam pharmacodynamics pathwayCyp2b3
methadone pharmacodynamics pathwayCyp2b3 , Cyp2d4
methadone pharmacokinetics pathwayCyp2b3 , Cyp2d4
mycophenolic acid pharmacokinetics pathwayCyp3a9
nabumetone pharmacodynamics pathwayCyp2b3
naproxen pharmacodynamics pathwayCyp2b3
neviparine pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a9
nicotine pharmacodynamics pathwayCyp2b3 , Fmo3 , Ugt1a5
nicotine pharmacokinetics pathwayCyp2b3 , Fmo3 , Ugt1a5
O-linked glycan biosynthetic pathwayUgt1a5
paracetamol drug pathwayCyp2b3
paracetamol pharmacokinetics pathwayCyp2d4 , Sult1a1 , Sult2a1
pentose and glucuronate interconversion pathwayUgt1a5
phase I biotransformation pathway via cytochrome P450Cyp2b3 , Cyp2d4 , Cyp3a2 , Cyp3a23/3a1 , Cyp3a9 , Fmo1 , Fmo3 , Ugt1a5
phenytoin pharmacodynamics pathwayUgt1a5
piroxicam pharmacodynamics pathwayCyp2b3
porphyrin and chlorophyll metabolic pathwayUgt1a5
retinol metabolic pathwayCyp2b3 , Cyp3a2 , Cyp3a23/3a1 , Cyp3a9 , Ugt1a5
salicylic acid pharmacodynamics pathwayCyp2b3
serotonin signaling pathway via receptors engaging G alphas protein familyEsr1
sodium salicylate pharmacodynamics pathwayCyp2b3
sorafenib pharmacokinetics pathwayCyp2b3
starch and sucrose metabolic pathwayUgt1a5
steroid hormone biosynthetic pathwayCyp3a2 , Cyp3a23/3a1 , Cyp3a9 , Ugt1a5
sulfite oxidase deficiency pathwaySult1a1
sulfur metabolic pathwaySult1a1
sulindac pharmacodynamics pathwayCyp2b3
tamoxifen pharmacodynamics pathwayCyp2b3 , Cyp2d4 , Cyp3a9 , Esr1 , Fmo1 , Fmo3 , Sult1a1 , Ugt1a5
tamoxifen pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a2 , Cyp3a23/3a1 , Cyp3a9 , Esr1 , Fmo1 , Fmo3 , Sult1a1 , Sult2a1 , Ugt1a5
teniposide pharmacodynamics pathwayCyp3a9
teniposide pharmacokinetics pathwayCyp3a9
tenoxicam pharmacodynamics pathwayCyp2b3
testosterone biosynthetic pathwaySult2a1
tiaprofenic acid pharmacodynamics pathwayCyp2b3
tolmetin pharmacodynamics pathwayCyp2b3
tramadol pharmacokinetics pathwayCyp2b3 , Cyp2d4
valdecoxib pharmacodynamics pathwayCyp2b3
valproic acid pharmacokinetics pathwayCyp2b3
venlafaxine pharmacokinetics pathwayCyp2d4
vitamin A deficiency pathwayCyp2b3 , Cyp3a9
Phenotype Annotations Associated with Genes in the tamoxifen pharmacokinetics pathway

References Associated with the tamoxifen pharmacokinetics pathway:

Ontology Path Diagram:

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