m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0028)
Name
Fulvestrant
Synonyms
Faslodex; AstraZeneca brand of fulvestrant; Fulvestrant [USAN]; Ici 182780; ZD 182780; ZM 182780; Faslodex (TN); ZD-182780; ZD-9238; ZM-182780; Faslodex(ICI 182,780); Faslodex, ICI 182780, Fulvestrant; Fulvestrant (JAN/USAN/INN); (7R,13S,17S)-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol; (7R,8R,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; (7R,8S,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl) nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; (7alpha,17beta)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1,3,5(10)-triene-3,17-diol; 7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)estra-1,3,5(10)-triene-3,17-diol; 7alpha-(9-((4,4,5,5,5,-Pentafluoropentyl)sulfinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol; 7alpha-(9-((4,4,5,5,5-Pentafluoropentyl)sulfinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol; 7alpha-[9[(4,4,5,5,5-Pentafluropentyl)sulfinyl]nonyl]-estra-1,3,5(10)-triene-3, 17 beta diol; ICI
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Status Approved [1]
Structure
Formula
C32H47F5O3S
InChI
InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1
InChIKey
VWUXBMIQPBEWFH-WCCTWKNTSA-N
PubChem CID
104741
TTD Drug ID
D0JO7Y
DrugBank ID
DB00947
Full List of m6A Targets Related to This Drug
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 [2]
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
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 [2]
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 [3]
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 [3]
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 [3]
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 [3]
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 [3]
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 [3]
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 [3]
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: 1015).
Ref 2 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 3 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.