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Drug

D0116 | Tamoxifen

Molecular Formula C26H29NO
Molecular Weight 371.5
Structure
State solid
Clearance Clearance (CL/F) as body weight adjusted in female pediatric patients was approximately 2.3-fold higher than in female breast cancer patients.
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.
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.
Trade names Nolvadex, Genox, Tamifen
Description non-steroidal antiestrogen used to treat estrogen receptor positive breast cancers; selective estrogen receptor modulator

L

L02BA01 Tamoxifen


[L02BA] Anti-estrogens


[L02B] HORMONE ANTAGONISTS AND RELATED AGENTS


[L02] ENDOCRINE THERAPY


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
OPENING OF PERMEABILITY TRANSITION PORE (PTP) 100 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
UNCOUPLING increase 46
ELECTROPHORETIC UNCOUPLING 278
MEMBRANE POTENTIAL 2.9 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
MEMBRANE POTENTIAL 100 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity decrease p < 0.001 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity decrease p < 0.001 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity decrease p < 0.001 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity decrease p < 0.001 3
ELECTRON TRANSPORT CHAIN 15 μM bovine heart mitochondria Measurement of complex II + III activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 15 μM bovine heart mitochondria Measurement of complex II + III activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 26.6 μM bovine heart mitochondria Measurement of complex IV activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 8.1 μM bovine heart mitochondria Measurement of complex V activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 4 μM bovine heart mitochondria Measurement of complex I activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 1.6 μM bovine heart mitochondria Measurement of complex V activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 30 μM bovine heart mitochondria Measurement of complex II + III activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 30 μM bovine heart mitochondria Measurement of complex II + III activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 29 μM bovine heart mitochondria Measurement of complex V activity decrease IC50 3
ELECTRON TRANSPORT CHAIN 26 μM bovine heart mitochondria Measurement of complex V activity decrease IC50 3
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 46
GLUCOSE GALACTOSE IC50 RATIO 97.9 ± 28.0, 64.4 ± 11.4, 1.5, 75.2 ± 8.4, 43.9 ± 7.8, 1.7 4hr H9c2 cells high-glucose–galactose cell viability assay with JC-1 mitochondrial membrane potential and ATP-depletion assays (CellTiter-Glo reagent ). glucose/galactose IC50 ratio (JC-1 IC50 in glucose, JC-1 IC50 in galactose, JC-1 glu/gla, ATP IC50 in glucose, ATP IC50 in galactose, ATP glu/gla ) 50
MITOCHONDRIAL FATTY ACID BETA OXIDATION affect 227
MITOCHONDRIAL FATTY ACID BETA OXIDATION affect 227
MITOCHONDRIAL FATTY ACID BETA OXIDATION 4μM 11 mice Lean mice vs Ob/ob mice Measurement of oxygen consumption in the presence of ADP (state 3) and the different substrates was carried out on the Mitologics screening platform EC20 227
SWELLING 9 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
ROS PRODUCTION 5 µM 1 hour Human HepG2 High-content screening assay Increase MEC 306

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase 15 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor IC50 3
NADH:ubiquinone reductase 4 μM bovine heart mitochondria Measurement of complex I activity inhibitor IC50 3
NADH:ubiquinone reductase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
Succinate dehydrogenase 50 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor p < 0.001 3
Succinate dehydrogenase 15 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor IC50 3
Succinate dehydrogenase 30 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor IC50 3
Succinate dehydrogenase inhibitor 35
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor p < 0.001 3
Quinol--cytochrome-c reductase 26.6 μM bovine heart mitochondria Measurement of complex IV activity inhibitor IC50 3
Quinol--cytochrome-c reductase 30 μM bovine heart mitochondria Measurement of complex II + III activity inhibitor IC50 3
Quinol--cytochrome-c reductase inhibitor 35
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity inhibitor p < 0.001 3
Cytochrome c oxidase 8.1 μM bovine heart mitochondria Measurement of complex V activity inhibitor IC50 3
Cytochrome c oxidase inhibitor 35
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity inhibitor p < 0.001 3
ATP synthase 1.6 μM bovine heart mitochondria Measurement of complex V activity inhibitor IC50 3
ATP synthase 29 μM bovine heart mitochondria Measurement of complex V activity inhibitor IC50 3
ATP synthase 26 μM bovine heart mitochondria Measurement of complex V activity inhibitor IC50 3
ATP synthase inhibitor 35
carnitine palmitoyltransferases I inhibit 227
carnitine palmitoyltransferases I inhibit 227
Reactive oxygen species 5 µM 1 hour Human HepG2 High-content screening assay increase MEC 306
Cytochrome c 7.7 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 10 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H302 (70%): Harmful if swallowed [Warning Acute toxicity, oral]


H350 (100%): May cause cancer [Danger Carcinogenicity]


H360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H362 (60%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]


H372 (40%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H400 (40%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


H410 (40%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P263, P264, P270, P273, P281, P301+P312, P308+P313, P314, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

Aggregated GHS information provided by 4 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


H341 (25%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]


H350 (100%): May cause cancer [Danger Carcinogenicity]


H360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H362 (25%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]


H372 (75%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H410 (25%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P263, P264, P270, P273, P281, P301+P312, P308+P313, P314, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Adenocarcinoma

  • Albright's disease

  • Bone cancer metastatic

  • Bone pain

  • Brain neoplasm

  • Breast cancer stage IV

  • Carcinoid tumour

  • Cerebrovascular accident

  • Contralateral breast cancer

  • Deep vein thrombosis

  • Embolism

  • Endometrial cancer

  • Hyperplasia

  • Intraductal proliferative breast lesion

  • Lobular breast carcinoma in situ

  • Malignant melanoma

  • Menarche

  • Neoplasm

  • Neoplasm malignant

  • Pancreatic carcinoma

  • Pulmonary embolism

  • Sarcoma

  • Soft tissue disorder

  • Thrombocytopenia

  • Dry mouth (0.02)

  • Vulvovaginal candidiasis (0.04)

  • Abdominal pain

  • Alopecia

  • Amenorrhoea

  • Anaemia

  • Anxiety

  • Arthralgia

  • Arthritis

  • Arthropathy

  • Aspartate aminotransferase increased

  • Asthenia

  • Back pain

  • Blood bilirubin increased

  • Blood creatinine increased

  • Bone pain

  • Breast neoplasm

  • Breast pain

  • Bronchitis

  • Cardiovascular disorder

  • Cataract

  • Chest pain

  • Constipation

  • Cough

  • Cyst

  • Decreased appetite

  • Deep vein thrombosis

  • Depression

  • Dermatitis

  • Diarrhoea

  • Dizziness

  • Dyspepsia

  • Dyspnoea

  • Embolism

  • Endometrial cancer

  • Fatigue

  • Fluid retention

  • Flushing

  • Fracture

  • Gastrointestinal disorder

  • Gastrointestinal pain

  • Headache

  • Hip fracture

  • Hot flush

  • Hypercholesterolaemia

  • Hyperhidrosis

  • Hypersensitivity

  • Hypertension

  • Infection

  • Influenza

  • Injury

  • Insomnia

  • Lymphoedema

  • Menopausal symptoms

  • Menstrual disorder

  • Menstruation irregular

  • Mood swings

  • Multiple fractures

  • Musculoskeletal discomfort

  • Musculoskeletal pain

  • Myalgia

  • Nausea

  • Neoplasm

  • Oedema

  • Oedema peripheral

  • Oligomenorrhoea

  • Osteoarthritis

  • Osteoporosis

  • Ovarian cyst

  • Pain

  • Paraesthesia

  • Pharyngitis

  • Phlebitis superficial

  • Platelet count decreased

  • Pulmonary embolism

  • Rash

  • Sepsis

  • Sinusitis

  • Thrombocytopenia

  • Urinary tract infection

  • Vaginal discharge

  • Vaginal haemorrhage

  • Vaginal infection

  • Vaginal inflammation

  • Vomiting

  • Vulvovaginitis

  • Weight decreased

  • Weight increased

    • (2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine (E/Z)-Tamoxifen (Z)-1-(p-Dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene, trans-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine
    (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine (Z)-2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)-N,N-dimethylethan-1-amine (Z)-2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)-N,N-dimethylethanamine
    (Z)-2-(4-(1,2-diphenylbut-1-enyl)phenoxy)-N,N-dimethylethanamine (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine (IUPAC)
    (Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE (Z)-2-[p-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine 094ZI81Y45
    1-[4-(2-Dimethylaminoethoxy)phenyl]-1,2-diphenyl-1-butene 1-p-.beta.-Dimethylamino-ethoxyphenyl-trans-1,2-diphenylbut-1-ene 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene
    1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene 10331-EP2270008A1 10331-EP2270018A1
    10331-EP2272827A1 10331-EP2272832A1 10331-EP2275102A1
    10331-EP2277865A1 10331-EP2277876A1 10331-EP2280012A2
    10331-EP2281815A1 10331-EP2289892A1 10331-EP2292233A2
    10331-EP2292576A2 10331-EP2292614A1 10331-EP2292617A1
    10331-EP2295416A2 10331-EP2295426A1 10331-EP2295427A1
    10331-EP2298305A1 10331-EP2298746A1 10331-EP2298748A2
    10331-EP2298778A1 10331-EP2298780A1 10331-EP2301536A1
    10331-EP2301538A1 10331-EP2301933A1 10331-EP2305640A2
    10331-EP2305642A2 10331-EP2305671A1 10331-EP2305689A1
    10331-EP2308833A2 10331-EP2308855A1 10331-EP2308861A1
    10331-EP2311455A1 10331-EP2311825A1 10331-EP2311827A1
    10331-EP2311840A1 10331-EP2311842A2 10331-EP2316452A1
    10331-EP2316831A1 10331-EP2316832A1 10331-EP2316833A1
    10331-EP2316834A1 10331-EP2374454A1 10540-29-1
    1ya4 2-[4-[(1Z)-1,2-Diphenyl-1-buten-1-yl]phenoxy]-N,N-dimethylethanamine 2-[4-[(Z)-1,2-di(phenyl)but-1-enyl]phenoxy]-N,N-dimethylethanamine
    2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine 2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine 2-{4-[(1Z)-1,2-Diphenylbut-1-en-1-yl]phenoxy}-N,N-dimethylethan-1-amine
    2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}-N,N-dimethylethanamine 2060AH 540T291
    7728-73-6 A801229 AB00053547-16
    AB00053547-17 AB00053547-18 AB00053547_19
    AB00053547_20 AKOS022143035 AM84324
    AOB5640 AX8001839 B5965
    BDBM20607 BIDD:ER0008 BIDD:GT0009
    BIDD:PXR0003 BPBio1_000278 BRD-K93754473-001-02-9
    BRD-K93754473-048-04-6 BRD-K93754473-048-05-3 BRD-K93754473-048-10-3
    BSPBio_000252 BSPBio_001150 BSPBio_001982
    C07108 C26H29NO CAS-10540-29-1
    CCG-205277 CCRIS 3275 CHEBI:41774
    CHEMBL83 CS-2870 Citofen
    Crisafeno D08559 DB00675
    DSSTox_CID_14187 DSSTox_GSID_34187 DSSTox_RID_79121
    DTXSID1034187 Diemon EBD41546
    EC 234-118-0 EINECS 234-118-0 Ethanamine, 2-(4-((1Z)-1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-
    Ethanamine, 2-(4-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-, (Z)- Ethanamine, 2-[4-[(1Z)-1,2-diphenyl-1-buten-1-yl]phenoxy]-N,N-dimethyl- Ethanamine, 2-[4-[(1Z)-1,2-diphenyl-1-butenyl]phenoxy]-N,N-dimethyl-
    Ethylamine, N,N-dimethyl-2-(p-(1,2-diphenyl-1-butenyl)phenoxy)-, (Z)- GA9513 GTPL1016
    GTPL5384 HMS1362J11 HMS1792J11
    HMS1990J11 HMS2090N08 HMS2232C12
    HMS3261D09 HMS3403J11 HMS3411P04
    HSDB 6782 HY-13757A ICI 47699
    ICI-46,474 ICI-46474 ICI-47699
    ICI47699 ICI47699;Z-Tamoxifen;trans-Tamoxifen IDI1_000258
    IDI1_002170 Istubol KS-1472
    L024126 LP00494 LS-393
    Lopac0_001203 MFCD00010454 MLS001332535
    MLS001332536 NCGC00024928-01 NCGC00024928-03
    NCGC00024928-04 NCGC00024928-05 NCGC00024928-07
    NCGC00024928-08 NCGC00024928-09 NCGC00024928-10
    NCGC00024928-11 NCGC00024928-12 NCGC00024928-13
    NCGC00024928-14 NCGC00024928-15 NCGC00024928-16
    NCGC00024928-17 NCGC00024928-18 NCGC00024928-19
    NCGC00254455-01 NCGC00258795-01 NCGC00261179-01
    NKANXQFJJICGDU-QPLCGJKRSA-N NSC-727681 NSC727681
    Novaldex Oncomox Prestwick2_000146
    Prestwick3_000146 Q412178 QTL1_000079
    Retaxim SBI-0051170.P004 SC-45564
    SCHEMBL4084 SMR000059172 ST24049322
    ST24049323 Soltamox Spectrum5_001417
    Spectrum5_002043 TAMOXIFEN (TAMOXIFEN CITRATE (54965-24-1)) TRANS FORM OF TAMOXIFEN
    Tamizam Tamoplex (TN) Tamoxen
    Tamoxifen (INN) Tamoxifen (TN) Tamoxifen (Z)
    Tamoxifen Drug Standard Solution Tamoxifen [INN:BAN] Tamoxifen and its salts
    Tamoxifen, 7 Tamoxifen, >=99% Tamoxifen, analytical standard
    Tamoxifen, certified reference material, TraceCERT(R) Tamoxifene Tamoxifene [INN-French]
    Tamoxifeno Tamoxifeno [INN-Spanish] Tamoxifenum
    Tamoxifenum [INN-Latin] Tocris-0999 Tomaxithen
    Tox21_201243 Tox21_300539 Tox21_500494
    UNII-094ZI81Y45 UPCMLD-DP027 VA11813
    Valodex W-108788 ZINC1530689
    [3H]-tamoxifen [3H]tamoxifen cMAP_000044
    cid_2733526 tamoxifen trans-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine
    trans-Tamoxifen

    DrugBank Name Tamoxifen
    DrugBank DB00675
    CAS Number 10540-29-1, 13002-65-8, 15917-50-7, 54965-24-1, 7728-73-6
    PubChem Compound 2733526
    KEGG Compound ID C07108
    KEGG Drug D08559
    PubChem.Substance 46505515
    ChEBI 41774
    PharmGKB PA451581
    ChemSpider 2015313
    BindingDB 20607.0
    TTD DAP000108
    Wikipedia Tamoxifen
    HET CTX
    DPD 11164|2137

    1. Dykens et al. (2007)
    2. Tanner et al., 2011