TAMOXIFEN PHARMACODYNAMICS PATHWAY (PW:0000839)

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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. tamoxifen membrane tethered ERs - rapid, non-genomic effects endoxifen 4-OH-TAM breast neoplasms Esr1 Esr2 estrogen signaling pathway supressed target gene expression ---| breast neoplasms tamoxifen pharmacokinetics pathway Ncoa3 --+> Esr1 Esr1 ---> tamoxifen resistance 4-OH-TAM ---- Esr2 endoxifen ---- Esr1 Esr2 ---- tamoxifen Esr1 ---- tamoxifen Ncoa3 mERs ---> tamoxifen resistance mERs endoxifen ---- Esr2 4-OH-TAM ---- Esr1 drug-bound ER corepressors ---| Esr1 tamoxifen resistance tumor growth supressed target gene expression Esr2 ---| supressed target gene expression Esr1 ---- Ncoa3 supressed target gene expression ---| tumor growth Esr1 ---| supressed target gene expression mERs ---- tamoxifen drug-bound ER corepressors ---- Esr1 drug-bound ER corepressors
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Genes in Pathway:

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tamoxifen pharmacodynamics 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 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:5130191
RGD:10402751
G Esr2 estrogen receptor 2 JBrowse link 6 99,163,953 99,214,711 RGD:5130191
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 Ncoa3 nuclear receptor coactivator 3 JBrowse link 3 162,692,176 162,788,582 RGD:5130718
G Ncor1 nuclear receptor co-repressor 1 JBrowse link 10 48,629,121 48,772,890 RGD:5130718
G Ncor2 nuclear receptor co-repressor 2 JBrowse link 12 36,871,917 37,033,701 RGD:5130718
G Phb2 prohibitin 2 JBrowse link 4 157,230,769 157,235,375 RGD:5130718
G Sult1a1 sulfotransferase family 1A member 1 JBrowse link 1 198,100,586 198,104,106 RGD:10402751
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 Moleculeendoxifenendoxifen
Diseasebreast neoplasmsentry point to the cancer disease portal
Small Moleculetamoxifentamoxifen

Pathway Gene Annotations

Disease Annotations Associated with Genes in the tamoxifen pharmacodynamics pathway
Disease TermsGene Symbols
acute kidney failureCyp2d4
acute myeloid leukemiaCyp2d4
Acute-Phase ReactionNcor1
adenocarcinomaEsr1 , Esr2 , Ncoa3
adenomaEsr2
alopeciaEsr2
Alzheimer's diseaseCyp2d4 , Esr1 , Esr2
amphetamine abuseCyp2d4
amyotrophic lateral sclerosis type 1Fmo1
Animal Disease ModelsEsr1
anxiety disorderEsr2 , Ncor1
aortic valve stenosisEsr2
ARC syndromeCyp2b3
arteriosclerosisEsr1
asthmaEsr2
astrocytomaEsr1 , Esr2 , Ncoa3
atherosclerosisEsr1 , Esr2
autoimmune hepatitisCyp2d4
Autosomal Recessive Spinocerebellar Ataxia 8Esr1
basal ganglia diseaseCyp2d4
benign neoplasmSult1a1
bilirubin metabolic disorderUgt1a5
Blast CrisisEsr2
bone diseaseEsr1
Bone FracturesEsr1
Bone NeoplasmsNcoa3
BradycardiaCyp2d4
Brain InjuriesPhb2
brain ischemiaEsr2
breast cancerEsr1 , Esr2 , Sult1a1
Breast Cancer, FamilialEsr1 , Ncor1
Breast NeoplasmsCyp2d4 , Esr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Sult1a1
Bronchial HyperreactivityEsr1
carcinomaEsr1 , Esr2
Cardiac ArrhythmiasEsr2
cataract 33Esr1
Cell Transformation, NeoplasticEsr1
cerebellar ataxiaEsr1
Chemical and Drug Induced Liver InjuryCyp2b3 , Fmo3
Chemotherapy-Induced Febrile NeutropeniaCyp3a9
Chromosome AberrationsSult1a1
chronic myeloid leukemiaCyp3a9
Chronic PeriodontitisEsr1
Cocaine-Related DisordersEsr2
Cognition DisordersCyp2d4
Cognitive DysfunctionEsr2
colitisEsr2
Colonic NeoplasmsEsr2 , Sult1a1
Colorectal NeoplasmsEsr2 , Sult1a1
ComaCyp2d4
contact dermatitisEsr2
coronary artery diseaseEsr1 , Esr2
Coronary DiseaseEsr2
Crigler Najjar Syndrome, Type 2Ugt1a5
Crigler-Najjar syndromeUgt1a5
Crohn's diseaseEsr2
cryptorchidismEsr1
cystitisEsr2
DeafnessEsr2
Developmental DisabilitiesNcor1
Diabetic NephropathiesEsr1
Disease ProgressionEsr1
Drug-Induced DyskinesiaCyp2d4
Drug-Induced LeukopeniaCyp3a9
Drug-induced NeutropeniaCyp3a9
Drug-Related Side Effects and Adverse ReactionsCyp2b3 , Cyp2d4
dystoniaCyp2d4
EFAVIRENZ, POOR METABOLISM OFCyp2b3
Emery-Dreifuss muscular dystrophyEsr1
end stage renal failureCyp2b3
endometrial cancerSult1a1
Endometrial NeoplasmsEsr1 , Esr2 , Ncor2 , Sult1a1
Endometrioid CarcinomasEsr1
endometriosisEsr1 , Esr2 , Ncor1
epilepsy with generalized tonic-clonic seizuresCyp2d4
esophagus squamous cell carcinomaSult1a1
essential hypertensionCyp3a9
Estrogen ResistanceEsr1
Experimental ArthritisEsr1 , Esr2
Experimental Autoimmune EncephalomyelitisEsr2
Experimental Diabetes MellitusCyp2b3 , Esr1
Experimental Liver CirrhosisCyp2d4 , Cyp3a9 , Fmo1 , Ncor2
familial adenomatous polyposisFmo3
Female InfertilityEsr1 , Esr2
Female Urogenital DiseasesEsr1
FeminizationEsr1
genetic diseaseUgt1a5
Genomic InstabilitySult1a1
Gilbert syndromeUgt1a5
glioblastoma multiformeNcor1
gliosarcomaCyp2b3
glomerulonephritisEsr1
glomerulosclerosisEsr2
Graves' diseaseEsr2
Hashimoto DiseaseEsr2
Hearing LossEsr2
Hepatitis C, ChronicCyp2d4
hepatocellular carcinomaEsr1
Hot FlashesEsr2
Huntington's diseaseNcor1
HyperalgesiaEsr1 , Esr2
Hyperbilirubinemia, NeonatalNcor1
Hyperbilirubinemia, Transient Familial NeonatalUgt1a5
hypertensionEsr2 , Fmo3
Hypertrophy, Left VentricularEsr2
hypospadiasEsr2
HypotensionSult1a1
hypothyroidismNcor1
in situ carcinomaEsr1 , Esr2
infertilityEsr1
inflammatory bowel diseaseEsr2
inherited metabolic disorderFmo3
interstitial cystitisEsr2
interstitial nephritisCyp2d4
kidney diseaseCyp3a9
leiomyomaEsr1
leukemiaEsr1 , Ncoa3
Leukemia, Myeloid, Chronic-PhaseCyp3a9
Leydig cell tumorEsr1
LithiasisEsr2
liver neoplasmEsr1 , Ncor1
lung adenocarcinomaSult1a1
lung cancerSult1a1
Lung InjuryEsr2
Lung NeoplasmsEsr1
lung squamous cell carcinomaSult1a1
lymphangioleiomyomatosisEsr1
macular degenerationEsr1
male infertilityEsr1
Mammary Neoplasms, AnimalEsr1 , Esr2
Mammary Neoplasms, ExperimentalEsr1 , Esr2
Manganese PoisoningCyp2d4
medulloblastomaEsr2
melanomaEsr1 , Esr2
Melanoma, ExperimentalEsr2
mental depressionEsr2
MesotheliomaEsr1
Metabolic Bone DiseasesEsr1
migraineEsr1
MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 1Esr1
multiple myelomaCyp2d4
Muscle RigidityCyp2d4
Musculoskeletal PainEsr1
myasthenia gravisEsr2
myelofibrosisNcor2
myeloid leukemiaEsr2
myocardial infarctionEsr1
Myocardial IschemiaSult1a1
Myocardial Reperfusion InjuryEsr1 , Esr2
Neoplasm InvasivenessEsr1
Neoplasm MetastasisEsr1
Neoplasm Recurrence, LocalEsr1
nephrosisCyp3a9
neuroblastomaEsr1
non-small cell lung carcinomaEsr1 , Ncoa3
obesityEsr1 , Esr2 , Ncoa3
Occupational DiseasesCyp2d4
oligospermiaEsr1
osteoarthritisEsr1 , Ncor2
Osteoarthritis, HandEsr1 , Esr2
Osteoarthritis, HipEsr1
Osteoarthritis, KneeEsr1 , Esr2
osteoporosisEsr1 , Esr2
Osteoporosis, PostmenopausalEsr1 , Esr2
Osteoporotic FracturesEsr1 , Esr2
Ovarian NeoplasmsEsr1 , Sult1a1
Parkinson's diseaseCyp2d4 , Esr2
Parkinsonian DisordersEsr1
peritonitisEsr1 , Esr2
Pituitary NeoplasmsEsr2
pleomorphic xanthoastrocytomaCyp3a9
pleurisyEsr1
polycystic ovary syndromeNcor1
Poor Drug Metabolism, CYP2D6-RelatedCyp2d4
pre-eclampsiaEsr2
precursor B lymphoblastic lymphoma/leukemiaCyp3a9
precursor lymphoblastic lymphoma/leukemiaCyp2d4 , Cyp3a9
Prenatal Exposure Delayed EffectsCyp2d4
primary immunodeficiency diseaseCyp3a9
primary open angle glaucomaEsr2
prostate cancerEsr2
prostate carcinoma in situEsr1 , Esr2
prostatic hypertrophyEsr1 , Esr2
Prostatic NeoplasmsCyp2d4 , Cyp3a9 , Esr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Sult1a1
pulmonary hypertensionEsr1 , Esr2
Reperfusion InjuryCyp3a9
retinal degenerationEsr2
rheumatoid arthritisEsr2
schizophreniaSult1a1
SepsisEsr2
sexual disorderCyp2d4
Shock, HemorrhagicEsr1 , Esr2
Spinal Cord InjuriesEsr1 , Esr2
Spinal FracturesEsr1
SplenomegalyEsr2
squamous cell carcinomaNcoa3
Stomach NeoplasmsSult1a1
StrokeEsr2
Subarachnoid HemorrhageEsr1
substance-induced psychosisEsr1
substance-related disorderCyp2d4
systemic lupus erythematosusEsr2
systemic sclerodermaEsr1 , Esr2
thrombosisCyp3a9
Tobacco Addiction, Susceptibility ToCyp2b3
toxic encephalopathyCyp3a9
transient cerebral ischemiaEsr1 , Esr2
transitional cell carcinomaEsr2 , Ncor1
TremorCyp2d4
TrimethylaminuriaFmo3
type 2 diabetes mellitusEsr1
ulcerative colitisEsr2
urinary bladder cancerEsr1 , Esr2 , Ncor1 , Sult1a1
Urination DisordersEsr1 , Esr2
Urologic NeoplasmsSult1a1
Varicose UlcerEsr1 , Esr2
vitiligoEsr1
Vulvar Lichen SclerosusEsr1 , Esr2
Weight GainCyp2d4
Pathway Annotations Associated with Genes in the tamoxifen pharmacodynamics pathway
Pathway TermsGene Symbols
acetylsalicylic acid pharmacodynamics pathwayCyp2b3
aldosterone signaling pathwayNcor1 , Ncor2
altered androgen signaling pathwayNcor2
androgen signaling pathwayNcoa3 , Ncor1 , Ncor2
antipyrine drug pathwayCyp2b3
arachidonic acid metabolic pathwayCyp2b3
artemether pharmacokinetics pathwayCyp3a9
ascorbate and aldarate metabolic pathwayUgt1a5
bisphenol A response pathwayEsr1 , Esr2
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
cortisol signaling pathwayNcoa3 , Ncor1 , Ncor2
cyclophosphamide pharmacodynamics pathwayCyp2b3
cyclophosphamide pharmacokinetics pathwayCyp2b3
desipramine pharmacodynamics pathwayCyp2d4
desipramine pharmacokinetics pathwayCyp2d4
diclofenac pharmacodynamics pathwayCyp2b3
diflunisal pharmacodynamics pathwayCyp2b3
doxepin pharmacokinetics pathwayCyp2d4
estrogen signaling pathwayEsr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Phb2
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 , Ncoa3
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 pathwayCyp3a9
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
mitochondria fusion pathwayPhb2
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
Notch signaling pathwayNcor1 , Ncor2
nuclear factor, erythroid 2 like 2 signaling pathwayNcoa3
O-linked glycan biosynthetic pathwayUgt1a5
paracetamol drug pathwayCyp2b3
paracetamol pharmacokinetics pathwayCyp2d4 , Sult1a1
pentose and glucuronate interconversion pathwayUgt1a5
phase I biotransformation pathway via cytochrome P450Cyp2b3 , Cyp2d4 , Cyp3a9 , Fmo1 , Fmo3 , Ugt1a5
phenytoin pharmacodynamics pathwayUgt1a5
piroxicam pharmacodynamics pathwayCyp2b3
porphyrin and chlorophyll metabolic pathwayUgt1a5
prostate cancer pathwayNcor2
retinoic acid signaling pathwayNcoa3 , Ncor1 , Ncor2
retinol metabolic pathwayCyp2b3 , 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 pathwayCyp3a9 , Ugt1a5
sulfite oxidase deficiency pathwaySult1a1
sulfur metabolic pathwaySult1a1
sulindac pharmacodynamics pathwayCyp2b3
tamoxifen pharmacodynamics pathwayCyp2b3 , Cyp2d4 , Cyp3a9 , Esr1 , Esr2 , Fmo1 , Fmo3 , Ncoa3 , Ncor1 , Ncor2 , Phb2 , Sult1a1 , Ugt1a5
tamoxifen pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a9 , Esr1 , Fmo1 , Fmo3 , Sult1a1 , Ugt1a5
teniposide pharmacodynamics pathwayCyp3a9
teniposide pharmacokinetics pathwayCyp3a9
tenoxicam pharmacodynamics pathwayCyp2b3
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 pharmacodynamics pathway

References Associated with the tamoxifen pharmacodynamics pathway:

Ontology Path Diagram:

paths to the root

Import into Pathway Studio: