Drug Details

General Information of the Drug (ID: DR5291)
Name
4-hydroxy-tamoxifen
Synonyms
4'-hydroxytamoxifen; 82413-23-8; 4-Hydroxy-tamoxifen; (Z)-4'-hydroxytamoxifen; CHEMBL10041; trans-Hydroxytamoxifen; 4-[(Z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol; 4-HT; 4-{(1Z)-1-[{4-[2-(dimethylamino)ethoxy]phenyl}(phenyl)methylene]propyl}phenol; 4Hydroxy Tamoxifen; NCGC00091028-01; GTPL2817; SCHEMBL2165503; DTXSID00873019; ZINC8602413; BDBM50180684; NCGC00091028-02; Q27073761; 4 inverted exclamation mark -Hydroxy Tamoxifen (contains up to 10% E isomer); 4-[(Z)-1-[4-(2-dimethylaminoethyloxy)phenyl]-1-phenylbut-1-en-2-yl] phenol; 4HT
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Molecular Type
Small molecule
Disease Cyclic Mastalgia [ICD-11: GB23] Phase 2 [1]
Structure
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2D MOL

3D MOL

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Formula
C26H29NO2
PubChem CID
5284643
Canonical SMILES
CCC(=C(C1=CC=CC=C1)C2=CC=C(C=C2)OCCN(C)C)C3=CC=C(C=C3)O
InChI
1S/C26H29NO2/c1-4-25(20-10-14-23(28)15-11-20)26(21-8-6-5-7-9-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-
InChIKey
DODQJNMQWMSYGS-QPLCGJKRSA-N
CAS Number
CAS 82413-23-8
TTD Drug ID
D0B4VV
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Betulinic Acid      Rubus alceifolius     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		 Down-regulation Expression PYGO2  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
MDA-MB-436 CVCL_0623 Invasive breast carcinoma Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Selective estrogen receptor modulators and betulinic acid act synergistically to target ERalpha and SP1 transcription factor dependent Pygopus expression in breast cancer.
          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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Apoptosis
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic cytotoxicity elicited by the combination of EGCG and 4-OHT results from an earlier induction of apoptosis but this was not caused by an increase in G1-arrest or 4-OHT-mediated changes in the metabolism of EGCG.
          Flavopiridol      Dysoxylum binectariferum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     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 Activity CASP2  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Arrest Cell cycle arrest in G2 phase
                    In-vitro Model MON CVCL_M846 Extrarenal rhabdoid tumor Homo sapiens
G-401 CVCL_0270 Rhabdoid tumor of the kidney Homo sapiens
A-204 CVCL_1058 Embryonal rhabdomyosarcoma Homo sapiens
                    Experimental
                    Result(s)		 Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis.
          Shikonin      Lithospermum erythrorhizon     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 BID  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Down-regulation Loss of mitochondrial membrane potential
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-435S CVCL_0622 Breast cancer Homo sapiens
                    In-vivo Model Portions of the suspension (6*106 MCF-7 cells in 0.1 mL) were subcutaneously injected into the right fanks of each female nude mice.
                    Experimental
                    Result(s)		 Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo.
Target and Pathway
Target(s) Estrogen receptor (ESR)  Molecule Info  [6]
Oestrogen receptor beta (ESR2)  Molecule Info  [6]
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
12 Validated nuclear estrogen receptor beta 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
11 SIDS Susceptibility Pathways
12 Ovarian Infertility Genes
References
Reference 1 ClinicalTrials.gov (NCT00272714) Study of Afimoxifene Gel to Treat Cyclic Mastalgia in Premenopausal Women
Reference 2 Selective estrogen receptor modulators and betulinic acid act synergistically to target ERalpha and SP1 transcription factor dependent Pygopus expression in breast cancer. J Clin Pathol. 2016 Jun;69(6):518-26.
Reference 3 Potential mechanisms for the synergistic cytotoxicity elicited by 4-hydroxytamoxifen and epigallocatechin gallate in MDA-MB-231 cells. Int J Oncol. 2007 Jun;30(6):1407-12.
Reference 4 Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen. BMC Cancer. 2010 Nov 19;10:634.
Reference 5 Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo. Chin Med. 2020 Mar 10;15:23.
Reference 6 Antagonists selective for estrogen receptor alpha. Endocrinology. 2002 Mar;143(3):941-7.
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