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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

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 Cyp3a18 cytochrome P450, family 3, subfamily a, polypeptide 18 JBrowse link 12 10,636,294 10,684,273 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
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

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 InjuryCyp2d4
Acute-Phase ReactionNcor1
AdenocarcinomaEsr1 , Esr2 , Ncoa3
Adenomatous Polyposis ColiFmo3
Alzheimer DiseaseCyp2d4 , Esr1 , Esr2
Amphetamine-Related DisordersCyp2d4
Amyotrophic Lateral Sclerosis 1Fmo1
Anxiety DisordersEsr2 , Ncor1
Aortic Valve StenosisEsr2
Arrhythmias, CardiacEsr2
Arthritis, ExperimentalEsr1 , Esr2
Arthritis, RheumatoidEsr2
AstrocytomaEsr1 , Esr2 , Ncoa3
AtherosclerosisEsr1 , Esr2
Basal Ganglia DiseasesCyp2d4
Blast CrisisEsr2
Bone Diseases, MetabolicEsr1
Bone NeoplasmsNcoa3
Brain InjuriesPhb2
Brain IschemiaEsr2
breast cancerEsr1
Breast Cancer, FamilialEsr1 , Ncor1
Breast NeoplasmsCyp2d4 , Cyp3a18 , Esr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Sult1a1
Bronchial HyperreactivityEsr1
CarcinomaEsr1 , Esr2
Carcinoma in SituEsr1 , Esr2
Carcinoma, EndometrioidEsr1
Carcinoma, HepatocellularEsr1
Carcinoma, Non-Small-Cell LungEsr1 , Ncoa3
Carcinoma, Squamous CellNcoa3
Carcinoma, Transitional CellEsr2 , Ncor1
Cataract, Cortical, Juvenile-OnsetEsr1
Cell Transformation, NeoplasticEsr1
Chemical and Drug Induced Liver InjuryFmo3
Chemotherapy-Induced Febrile NeutropeniaCyp3a9
Chromosome AberrationsSult1a1
Chronic PeriodontitisEsr1
Cocaine-Related DisordersEsr2
Cognition DisordersCyp2d4
Cognitive DysfunctionEsr2
Colonic NeoplasmsEsr2 , Sult1a1
Colorectal NeoplasmsEsr2 , Sult1a1
Coronary Artery DiseaseEsr1 , Esr2
Coronary DiseaseEsr2
Crohn DiseaseEsr2
Cystitis, InterstitialEsr2
Depressive DisorderEsr2
Dermatitis, ContactEsr2
Developmental DisabilitiesNcor1
Diabetes Mellitus, ExperimentalCyp2b3 , Esr1
Diabetes Mellitus, Type 2Esr1
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
Encephalomyelitis, Autoimmune, ExperimentalEsr2
Endometrial NeoplasmsEsr1 , Esr2 , Ncor2 , Sult1a1
EndometriosisEsr1 , Esr2 , Ncor1
Epilepsy, Tonic-ClonicCyp2d4
Estrogen ResistanceEsr1
Female Urogenital DiseasesEsr1
Fractures, BoneEsr1
Genomic InstabilitySult1a1
Glaucoma, Primary Open AngleEsr2
Graves DiseaseEsr2
Hashimoto DiseaseEsr2
Hearing LossEsr2
Hepatitis CCyp3a18
Hepatitis C, ChronicCyp2d4
Hepatitis, AutoimmuneCyp2d4
Hot FlashesEsr2
Huntington DiseaseNcor1
HyperalgesiaEsr1 , Esr2
HypertensionEsr2 , Fmo3
Hypertension, EssentialCyp3a9
Hypertension, PulmonaryEsr1 , Esr2
Hypertrophy, Left VentricularEsr2
Immunologic Deficiency SyndromesCyp3a9
Infertility, FemaleEsr1 , Esr2
Infertility, MaleEsr1
Inflammatory Bowel Disease 11Esr2
Inflammatory Bowel DiseasesEsr2
Ischemic Attack, TransientEsr1 , Esr2
Kidney DiseasesCyp3a9
Kidney Failure, ChronicCyp2b3
LeukemiaEsr1 , Ncoa3
Leukemia, Myelogenous, Chronic, BCR-ABL PositiveCyp3a9
Leukemia, MyeloidEsr2
Leukemia, Myeloid, AcuteCyp2d4
Leukemia, Myeloid, Chronic-PhaseCyp3a9
Leydig Cell TumorEsr1
Liver Cirrhosis, ExperimentalCyp2d4 , Cyp3a9 , Fmo1 , Ncor2
Liver NeoplasmsEsr1 , Ncor1
Lung InjuryEsr2
Lung NeoplasmsEsr1
Lupus Erythematosus, SystemicEsr2
Macular DegenerationEsr1
Mammary Neoplasms, AnimalEsr1 , Esr2
Mammary Neoplasms, ExperimentalEsr1 , Esr2
Manganese PoisoningCyp2d4
MelanomaEsr1 , Esr2
Melanoma, ExperimentalEsr2
Metabolism, Inborn ErrorsFmo3
Migraine DisordersEsr1
Multiple MyelomaCyp2d4
Muscle RigidityCyp2d4
Musculoskeletal PainEsr1
Myasthenia GravisEsr2
Myocardial InfarctionEsr1
Myocardial IschemiaSult1a1
Myocardial Reperfusion InjuryEsr1 , Esr2
Neoplasm InvasivenessEsr1
Neoplasm MetastasisEsr1
Neoplasm Recurrence, LocalEsr1
Nephritis, InterstitialCyp2d4
NephrosisCyp3a18 , Cyp3a9
Neurotoxicity SyndromesCyp3a9
ObesityEsr1 , Esr2 , Ncoa3
Occupational DiseasesCyp2d4
OsteoarthritisEsr1 , Ncor2
Osteoarthritis, HandEsr1 , Esr2
Osteoarthritis, HipEsr1
Osteoarthritis, KneeEsr1 , Esr2
OsteoporosisEsr1 , Esr2
Osteoporosis, PostmenopausalEsr1 , Esr2
Osteoporotic FracturesEsr1 , Esr2
Ovarian NeoplasmsEsr1 , Sult1a1
Parkinson DiseaseCyp2d4 , Esr2
Parkinsonian DisordersEsr1
PeritonitisEsr1 , Esr2
Pituitary NeoplasmsEsr2
Pleomorphic Xanthoastrocytoma Cyp3a18 , Cyp3a9
Polycystic Ovary SyndromeNcor1
Precursor B-Cell Lymphoblastic Leukemia-LymphomaCyp3a9
Precursor Cell Lymphoblastic Leukemia-LymphomaCyp2d4 , Cyp3a9
Prenatal Exposure Delayed EffectsCyp2d4
Prostatic HyperplasiaEsr1 , Esr2
Prostatic Intraepithelial NeoplasiaEsr1 , Esr2
Prostatic NeoplasmsCyp2d4 , Cyp3a18 , Cyp3a9 , Esr1 , Esr2 , Ncoa3 , Ncor2 , Sult1a1
Psychoses, Substance-InducedEsr1
Reperfusion InjuryCyp3a9
Retinal DegenerationEsr2
Scleroderma, SystemicEsr1 , Esr2
Sexual Dysfunctions, PsychologicalCyp2d4
Shock, HemorrhagicEsr1 , Esr2
Spinal Cord InjuriesEsr1 , Esr2
Spinal FracturesEsr1
Stomach NeoplasmsSult1a1
Subarachnoid HemorrhageEsr1
Substance-Related DisordersCyp2d4
Tobacco Addiction, Susceptibility ToCyp2b3
Torsades de PointesCyp3a18
Urinary Bladder NeoplasmsEsr1 , Esr2 , Ncor1 , Sult1a1
Urination DisordersEsr1 , Esr2
Urologic NeoplasmsSult1a1
Varicose UlcerEsr1 , Esr2
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 pathwayCyp3a18 , Cyp3a9
bisphenol A response pathwayEsr1 , Esr2
caffeine pharmacokinetics pathwayCyp3a18
carbamazepine pharmacokinetics pathwayCyp2b3 , Cyp3a18 , Cyp3a9
celecoxib pharmacodynamics pathwayCyp2b3 , Cyp2d4 , Cyp3a18
celecoxib pharmacokinetics pathwayCyp2d4 , Cyp3a18
citalopram pharmacodynamics pathwayCyp2d4
citalopram pharmacokinetics pathwayCyp2d4
clomipramine pharmacokinetics pathwayCyp2d4 , Cyp3a18
clopidogrel pharmacodynamics pathwayCyp2b3 , Cyp3a18 , Cyp3a9
clopidogrel pharmacokinetics pathwayCyp2b3 , Cyp3a18 , Cyp3a9
codeine and morphine pharmacodynamics pathwayCyp2d4 , Cyp3a18
codeine and morphine pharmacokinetics pathwayCyp2d4 , Cyp3a18
cortisol signaling pathwayNcoa3 , Ncor1 , Ncor2
cyclophosphamide pharmacodynamics pathwayCyp2b3 , Cyp3a18
cyclophosphamide pharmacokinetics pathwayCyp2b3 , Cyp3a18
desipramine pharmacodynamics pathwayCyp2d4
desipramine pharmacokinetics pathwayCyp2d4
diclofenac pharmacodynamics pathwayCyp2b3
diflunisal pharmacodynamics pathwayCyp2b3
doxepin pharmacokinetics pathwayCyp2d4 , Cyp3a18
estrogen signaling pathwayEsr1 , Esr2 , Ncoa3 , Ncor1 , Ncor2 , Phb2
etodolac pharmacodynamics pathwayCyp2b3
etoposide pharmacodynamics pathwayCyp3a18 , Cyp3a9
etoposide pharmacokinetics pathwayCyp3a18 , Cyp3a9
felbamate pharmacokinetics pathwayCyp3a18
fenoprofen pharmacodynamics pathwayCyp2b3
fluoxetine pharmacodynamics pathwayCyp2d4 , Cyp3a18 , Cyp3a9
fluoxetine pharmacokinetics pathwayCyp2d4 , Cyp3a18 , Cyp3a9
flurbiprofen pharmacodynamics pathwayCyp2b3
follicle-stimulating hormone signaling pathwayEsr1
forkhead class A signaling pathwayEsr1 , Ncoa3
histamine signaling pathway, immunologicalEsr1
ibuprofen pharmacodynamics pathwayCyp2b3 , Cyp3a18
ibuprofen pharmacokinetics pathwayCyp3a18
ifosfamide pharmacodynamics pathwayCyp2b3 , Cyp3a18 , Cyp3a9
ifosfamide pharmacokinetics pathwayCyp2b3 , Cyp3a18 , Cyp3a9
imipramine pharmacodynamics pathwayCyp2d4 , Cyp3a18
imipramine pharmacokinetics pathwayCyp2d4 , Cyp3a18
indometacin pharmacodynamics pathwayCyp2b3
indometacin pharmacodynamics pathwayCyp2b3
insulin-like growth factor signaling pathwayEsr1
irinotecan pharmacodynamics pathwayCyp3a18 , Cyp3a9
irinotecan pharmacokinetics pathwayCyp3a18 , Cyp3a9
ketoprofen pharmacodynamics pathwayCyp2b3
ketorolac pharmacodynamics pathwayCyp2b3
lamivudine pharmacokinetics pathwaySult1a1
leukotriene C4 synthase deficiency pathwayCyp2b3
lidocaine pharmacodynamics pathwayCyp3a18
lidocaine pharmacokinetics pathwayCyp3a18
linoleic acid metabolic pathwayCyp3a18 , Cyp3a9
lornoxicam pharmacodynamics pathwayCyp2b3
luteinizing hormone signaling pathwayEsr1
magnesium salicylate pharmacodynamics pathwayCyp2b3
mefenamic acid pharmacodynamics pathwayCyp2b3
meloxicam pharmacodynamics pathwayCyp2b3
methadone pharmacodynamics pathwayCyp2b3 , Cyp2d4 , Cyp3a18
methadone pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a18
mitochondria fusion pathwayPhb2
mycophenolic acid pharmacokinetics pathwayCyp3a18 , Cyp3a9
nabumetone pharmacodynamics pathwayCyp2b3
naproxen pharmacodynamics pathwayCyp2b3
neviparine pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a18 , Cyp3a9
nicotine pharmacodynamics pathwayCyp2b3 , Fmo3
nicotine pharmacokinetics pathwayCyp2b3 , Fmo3
Notch signaling pathwayNcor1 , Ncor2
nuclear factor, erythroid 2 like 2 signaling pathwayNcoa3
paracetamol drug pathwayCyp2b3
paracetamol pharmacokinetics pathwayCyp2d4 , Cyp3a18 , Sult1a1
phase I biotransformation pathway via cytochrome P450Cyp2b3 , Cyp2d4 , Cyp3a18 , Cyp3a9 , Fmo1 , Fmo3
phenytoin pharmacodynamics pathwayCyp3a18
piroxicam pharmacodynamics pathwayCyp2b3
prednisone pharmacodynamics pathwayCyp3a18
prednisone pharmacokinetics pathwayCyp3a18
prostate cancer pathwayNcor2
retinoic acid signaling pathwayNcoa3 , Ncor1 , Ncor2
retinol metabolic pathwayCyp2b3 , Cyp3a18 , Cyp3a9
salicylic acid pharmacodynamics pathwayCyp2b3
serotonin signaling pathway via receptors engaging G alphas protein familyEsr1
sodium salicylate pharmacodynamics pathwayCyp2b3
sorafenib pharmacokinetics pathwayCyp2b3 , Cyp3a18
steroid hormone biosynthetic pathwayCyp3a18 , Cyp3a9
sulfite oxidase deficiency pathwaySult1a1
sulfur metabolic pathwaySult1a1
sulindac pharmacodynamics pathwayCyp2b3
tamoxifen pharmacodynamics pathwayCyp2b3 , Cyp2d4 , Cyp3a18 , Cyp3a9 , Esr1 , Esr2 , Fmo1 , Fmo3 , Ncoa3 , Ncor1 , Ncor2 , Phb2 , Sult1a1
tamoxifen pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a18 , Cyp3a9 , Esr1 , Fmo1 , Fmo3 , Sult1a1
teniposide pharmacodynamics pathwayCyp3a18 , Cyp3a9
teniposide pharmacokinetics pathwayCyp3a18 , Cyp3a9
tenoxicam pharmacodynamics pathwayCyp2b3
tiaprofenic acid pharmacodynamics pathwayCyp2b3
tolmetin pharmacodynamics pathwayCyp2b3
tramadol pharmacokinetics pathwayCyp2b3 , Cyp2d4 , Cyp3a18
valdecoxib pharmacodynamics pathwayCyp2b3
valproic acid pharmacokinetics pathwayCyp2b3
venlafaxine pharmacokinetics pathwayCyp2d4 , Cyp3a18
vinblastine pharmacodynamics pathwayCyp3a18
vinorelbine pharmacodynamics pathwayCyp3a18
vitamin A deficiency pathwayCyp2b3 , Cyp3a18 , 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: