m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0039)
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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Status Approved [1]
Structure
Formula
C26H29NO
InChI
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
PubChem CID
2733526
TTD Drug ID
D07KSG
DrugBank ID
DB00675
Full List of m6A Targets Related to This Drug
Adenylate kinase 4, mitochondrial (AK4)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary Adenylate kinase 4 modulates the resistance of breast cancer cells to tamoxifen through an m6A-based epitranscriptomic mechanism. Genetic depletion of METTL3 in TamR MCF-7 cells led to a diminished Adenylate kinase 4, mitochondrial (AK4) protein level and attenuated resistance to tamoxifen.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Mitochondrial apoptosis
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF7-TamR Invasive breast carcinoma Homo sapiens CVCL_EG55
Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [3]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Myc proto-oncogene protein (MYC)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
Response Summary LCAT3 upregulation is attributable to m6A modification mediated by METTL3, leading to LCAT3 stabilization. Treated cells with tamoxifen to induce MYC activity. Highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in Myc proto-oncogene protein (MYC)-driven breast cancers.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Pathway Response MAPK signaling pathway hsa04010
Cell Process Epithelial-to-mesenchymal transition
Cell apoptosis
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MBA-MD-231 (Human breast cancer cell)
MYC-ER HMEC (Human mammary epithelial cells expressing a MYC estrogen receptor fusion)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
In-vivo Model To induce recombination at 8 weeks of age both CAG-CreERT;Ythdf2fl/fl and Ythdf2fl/fl littermates were injected with 75mg/kg body weight tamoxifen dissolved in corn oil daily for 5 days.
RAC-alpha serine/threonine-protein kinase (AKT1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [3]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated RAC-alpha serine/threonine-protein kinase (AKT1) and MAPK that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Ribonuclease 3 (DROSHA)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes Ribonuclease 3 (DROSHA) processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
microRNA 222 (MIR222)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and microRNA 222 (MIR222) and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
hsa-miR-1266-5p
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated hsa-miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
hsa-miR-1268a
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, hsa-miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
hsa-miR-29a-3p
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated hsa-miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
hsa-miR-29b-3p
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, hsa-miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
hsa-miR-671-3p
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary HNRNPA2B1 is a reader of the N(6)-methyladenosine mark in primary-miRNAs and promotes DROSHA processing to precursor-miRNAs. HNRNPA2B1 downregulated miR-29a-3p, miR-29b-3p, and miR-222 and upregulated miR-1266-5p, miR-1268a, hsa-miR-671-3p. Transient overexpression of HNRNPA2/B1 reduced breast cancer cellMCF-7 sensitivity to 4-hydroxytamoxifen and fulvestrant, suggesting a role for HNRNPA2/B1 in endocrine-resistance.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response TGF-beta signaling pathway hsa04350
Cell Process Endocrine-resistance
In-vitro Model MCF7/LCC9 Invasive breast carcinoma Homo sapiens CVCL_DP52
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
References
Ref 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).
Ref 2 Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m(6)A-Based Epitranscriptomic Mechanism. Mol Ther. 2020 Dec 2;28(12):2593-2604. doi: 10.1016/j.ymthe.2020.09.007. Epub 2020 Sep 5.
Ref 3 HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells. Cancer Lett. 2021 Oct 10;518:152-168. doi: 10.1016/j.canlet.2021.07.015. Epub 2021 Jul 14.
Ref 4 Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer. Mol Cell. 2021 Aug 5;81(15):3048-3064.e9. doi: 10.1016/j.molcel.2021.06.014. Epub 2021 Jul 2.
Ref 5 HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci Rep. 2019 Jul 1;9(1):9430. doi: 10.1038/s41598-019-45636-8.