m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02054
 [1]
DNA methylation DNMT3A IGFBP3 Direct Inhibition m6A modification m6A Target m6A Target IGFBP3 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor-binding protein 3 (IGFBP3) READER
 Regulator Info 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A) WRITER View Details
Regulated Target Insulin like growth factor binding protein 3 (IGFBP3) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary Because IGFBP3 is an established target of DNMT3A, we investigated the effect of MTA1 upon IGFBP3 expression, and found a coactivator role of MTA1/c-Jun/Pol II coactivator complex upon the IGFBP3 transcription. In addition, MTA1 overexpression correlates well with low levels of DNMT3A which, in turn also correlates with a high IGFBP3 status in breast cancer patients and predicts a poor clinical outcome for breast cancer patients.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
In-vitro Model
 MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MEF Fibrosarcoma Homo sapiens CVCL_C1M8
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cysteine methyltransferase DNMT3A (DNMT3A) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID27376512-Compound-Figure3CN Patented [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117968550
TTD: D02VTV
 Compound Name PMID27376512-Compound-Figure3CG Patented [2]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
CID: 117967861
TTD: D03LZO
 Compound Name PMID27376512-Compound-Figure3CM Patented [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117976053
TTD: D0F8AB
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [2]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
CID: 71521835
TTD: D01LUJ
 Compound Name PMID27376512-Compound-MTC-424 Patented [2]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [2]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [2]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [2]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
Insulin-like growth factor-binding protein 3 (IGFBP3) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Salvianolic acid B Phase 2 [3]
Synonyms
115939-25-8; 121521-90-2; Salvianolic-acid-B; Lithospermic acid B; MFCD07779133; (2R)-2-[(E)-3-[(2R,3R)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyl]oxy-3-(3,4-dihydroxyphenyl)propanoic acid; (R)-2-(((2R,3R)-4-((E)-3-((R)-1-Carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-en-1-yl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyl)oxy)-3-(3,4-dihydroxyphenyl)propanoic acid; Danshensuan B; Salcianolic acid B; C36H30O16; PubChem13035; CHEMBL3747259; ZINC49538629; AKOS015920258; AS-56980; S609; 939S258; (R)-2-((2R,3R)-4-((E)-3-((R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-enyl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyloxy)-3-(3,4-dihydroxyphenyl)propanoic acid; 1607436-77-0
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11629084
TTD: D2GV9Q
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [4]
Synonyms
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
    Click to Show/Hide
External Link
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [5]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
References
Ref 1 Metastasis-associated protein 1 is an upstream regulator of DNMT3a and stimulator of insulin-growth factor binding protein-3 in breast cancer. Sci Rep. 2017 Apr 10;7:44225. doi: 10.1038/srep44225.
Ref 2 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 3 Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3. J Mol Cell Cardiol. 2020 Feb;139:98-112.
Ref 4 Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372... Cancer Discov. 2017 Apr;7(4):400-409.
Ref 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015