Drug Details

General Information of the Drug (ID: DR1563)
Name
Tamoxifen
Synonyms
tamoxifen; 10540-29-1; trans-Tamoxifen; Crisafeno; Soltamox; Tamoxifene; Diemon; Tamoxifenum; Tamoxifeno; Tamizam; Istubol; Tamoxen; Citofen; Oncomox; Valodex; Retaxim; Tamoxifene [INN-French]; Tamoxifenum [INN-Latin]; Tamoxifeno [INN-Spanish]; Tamoxifen (Z); Tamoxifen and its salts; Tamoxifen [INN:BAN]; ICI-46474; ICI 47699; TRANS FORM OF TAMOXIFEN; CCRIS 3275; UNII-094ZI81Y45; HSDB 6782; CHEMBL83; EINECS 234-118-0; 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; Citofen; Nourytam; Novaldex; Tamone; Tamoxifeno; Tamoxifenum; Tomaxithen; Gen-Tamoxifen; Istubal (TN); Nolvadex (TN); Nolvadex-D; Novo-Tamoxifen; Pms-Tamoxifen; Tamoplex (TN); Tamoxifen (INN); Tamoxifen (TN); Trans-Tamoxifen; Valodex (TN); TAMOXIFEN (TAMOXIFEN CITRATE (54965-24-1)); Trans-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine; (Z)-1-(p-Dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene; (Z)-2-(4-(1,2-Diphenyl-1-butenyl)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 (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; 1-p-beta-Dimethylamino-ethoxyphenyl-trans-1,2-diphenylbut-1-ene; 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; 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-dimethylethanamine; Tamoxifen (Hormonal therapy); [3H]tamoxifen
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Molecular Type
Small molecule
Disease Breast cancer [ICD-11: 2C60] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 40 mcg/L
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 5 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability
Clearance
The clearance of drug is 189 mL/min in postmenopausal women
Elimination
Animal studies have shown 75% of radiolabelled tamoxifen recovered in the feces, with negligible collection from urine
Half-life
The concentration or amount of drug in body reduced by one-half in 5 - 7 days
Metabolism
The drug is metabolized via the hydroxylated to -hydroxytamoxifen
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.18283 micromolar/kg/day
Vd
The volume of distribution (Vd) of drug is 50-60 L/kg
Water Solubility
The ability of drug to dissolve in water is measured as 0.5 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C26H29NO
PubChem CID
2733526
Canonical SMILES
CCC(=C(C1=CC=CC=C1)C2=CC=C(C=C2)OCCN(C)C)C3=CC=CC=C3
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-
InChIKey
NKANXQFJJICGDU-QPLCGJKRSA-N
CAS Number
CAS 10540-29-1
ChEBI ID
CHEBI:41774
GDSC
Tamoxifen
TTD Drug ID
D07KSG
DrugBank ID
DB00675
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Carnosic acid      Salvia rosmarinus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TNFRSF10C  Molecule Info 
Pathway MAP
Up-regulation Expression TNFRSF10D  Molecule Info 
Pathway MAP
Up-regulation Expression TNFSF10  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
Up-regulation Expression TP73  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
                    In-vivo Model 5*105 MCF-7 cells were subcutaneously injected into the dorsal flanks of athymic nude mice.
                    Experimental
                    Result(s)		 Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression EZH2  Molecule Info 
Pathway MAP
Down-regulation Expression FAK  Molecule Info 
Pathway MAP
Down-regulation Expression IKKA  Molecule Info 
Pathway MAP
Down-regulation Expression IKKB  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RELA  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation SRC  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of curcumin and tamoxifen resulted in a synergistic survival inhibition in MCF-7/LCC2 and MCF-7/LCC9 cells.
          Cyclopamine      Veratrum californicum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression Gli1  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of cyclopamine and tamoxifen promotes survival and migration of mcf-7 breast cancer cells--interaction of hedgehog-gli and estrogen receptor signaling pathways.
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CYP1B1  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    In-vivo Model Female CD1 athymic nude mice were inoculated into the right flank with MDA-MB-231 cells (2*106/50L matrigel), which were left to form palpable tumours.
                    Experimental
                    Result(s)		 Tamoxifen at realistic doses (75 mug kg(-1)) can suppress the growth of ER-negative breast cancer when combined with EGCG. The dominant mechanism for tumour suppression is the concomitant decrease in tumour protein expressions of mTOR and the EGFR.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Expression ESR  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
                    In-vitro Model BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells.
          Methylselenocysteine      Astragalus bisulcatus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    In-vivo Model About 5*106 cells suspension in 50 uL sterile PBS were mixed with 100 uL Matrigel and administered within both sides of the inguinal mammary fat pad of NU/NU immune-compromised female ovariectomized mice.
                    Experimental
                    Result(s)		 These findings demonstrate synergistic growth inhibition of ERalpha positive breast cancer xenografts by combination of tamoxifen with organic selenium compounds.
          Oxyprogesterone caproate      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Oxyprogesterone caproate (OPC) administered preoperatively and after surgical and combined therapy from 6 up to 36 months increased the corrected survival rates as compared with that in patients who did not receive hormone treatment.
          Pancratistatin      Pancratium littorale     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Increase ROS generation
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 In combination with the anti-estrogen Tamoxifen, PST had a synergic effect.
          Pterostilbene      Vitis vinifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
ZR-75-1 CVCL_0588 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Pterostilbene shows an additive inhibitory effect on breast cancer cells when combined with tamoxifen, most likely from augmented cancer cell apoptosis.
          Thymoquinone      Nigella sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic effect of TQ and TAM on human breast cancer cell lines showed cell viability reduction as well as apoptosis induction, independent to estrogen.
          Vinblastine      Catharanthus roseus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy of breast and lung cancer cell lines using docetaxel or vinblastine with tamoxifen synergistically increases the anti-proliferative affect of single agents.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Vincamine      Vinca minor     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vivo Model Adult female Wistar albino rats were used in this study.
                    Experimental
                    Result(s)		 Zafirlukast and vincamine may be regarded as potential therapeutic strategies with antioxidant and anti-inflammatory activities against tamoxifen-induced oxidative damage in rat liver.
    γ. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Luteolin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCNE2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
BT-483 CVCL_2319 Invasive breast carcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
AU565 CVCL_1074 Breast adenocarcinoma Homo sapiens
MCF-10A CVCL_0598 Healthy Homo sapiens
                    Experimental
                    Result(s)		 Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression.
Target and Pathway
Target(s) Estrogen receptor (ESR)  Molecule Info  [15]
KEGG Pathway Estrogen signaling pathway Click to Show/Hide
2 Prolactin signaling pathway
3 Thyroid hormone signaling pathway
4 Endocrine and other factor-regulated calcium reabsorption
5 Proteoglycans in cancer
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
2 EGFR1 Signaling Pathway
3 RANKL Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Signaling events mediated by HDAC Class II
3 Plasma membrane estrogen receptor signaling
4 LKB1 signaling events
5 Regulation of Telomerase
6 ATF-2 transcription factor network
7 AP-1 transcription factor network
8 FOXM1 transcription factor network
9 Validated nuclear estrogen receptor alpha network
10 Signaling mediated by p38-alpha and p38-beta
11 FOXA1 transcription factor network
Reactome Nuclear signaling by ERBB4 Click to Show/Hide
2 Nuclear Receptor transcription pathway
WikiPathways Estrogen signaling pathway Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Estrogen Receptor Pathway
4 Signaling by ERBB4
5 JAK/STAT
6 Integrated Pancreatic Cancer Pathway
7 Leptin signaling pathway
8 miR-targeted genes in muscle cell - TarBase
9 Integrated Breast Cancer Pathway
10 Nuclear Receptors
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1016).
Reference 2 Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo. Biomed Pharmacother. 2017 May;89:827-837.
Reference 3 Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013 Jan 8;18(1):701-20.
Reference 4 Combination of cyclopamine and tamoxifen promotes survival and migration of mcf-7 breast cancer cells--interaction of hedgehog-gli and estrogen receptor signaling pathways. PLoS One. 2014 Dec 12;9(12):e114510.
Reference 5 A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate. Br J Cancer. 2008 Oct 7;99(7):1056-63.
Reference 6 Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Mol Carcinog. 2007 Jul;46(7):534-42.
Reference 7 Combination of methylselenocysteine with tamoxifen inhibits MCF-7 breast cancer xenografts in nude mice through elevated apoptosis and reduced angiogenesis. Breast Cancer Res Treat. 2009 Nov;118(1):33-43.
Reference 8 Favourable influence of adjuvant hormone therapy by oxyprogesterone caproate (OPC) and by its combination with tamoxifen on 5-year survival rate of surgical and combined treatment of primary endometrial carcinoma patients. Eur J Gynaecol Oncol. 1993;14(2):150-3.
Reference 9 Synergy of Pancratistatin and Tamoxifen on breast cancer cells in inducing apoptosis by targeting mitochondria. Cancer Biol Ther. 2008 Mar;7(3):376-84.
Reference 10 Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro. Am J Surg. 2010 Nov;200(5):577-80.
Reference 11 Thymoquinone Could Increase The Efficacy of Tamoxifen Induced Apoptosis in Human Breast Cancer Cells: An In Vitro Study. Cell J. Jul-Sep 2016;18(2):245-54.
Reference 12 Combination therapy increases the efficacy of docetaxel, vinblastine and tamoxifen in cancer cells. J Cancer Res Ther. Jul-Sep 2014;10(3):715-21.
Reference 13 Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK/ERK pathway. Life Sci. 2018 Jun 1;202:78-88.
Reference 14 Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression. Food Chem. 2013 Nov 15;141(2):1553-61.
Reference 15 Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
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