Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02102
[1]
DNA methylation DNMT3B METTL14 Direct Inhibition m6A modification MIR375 MIR375 METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
m6A Target microRNA 375 (MIR375)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 3B (DNMT3B) WRITER View Details
Regulated Target Methyltransferase-like protein 14 (METTL14) 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 lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-microRNA 375 (MIR375)-SOX12 axis.
Responsed Disease Breast cancer ICD-11: 2C60
In-vitro Model
MCF-10A Normal Homo sapiens CVCL_0598
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DNA (cytosine-5)-methyltransferase 3B (DNMT3B) 22 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Curcumin Phase 3 [2]
Synonyms
458-37-7; Diferuloylmethane; Natural yellow 3; Turmeric yellow; Turmeric; Curcuma; Kacha haldi; Gelbwurz; Indian saffron; Curcumin I; Souchet; Halud; Halad; Haidr; Haldar; Merita earth; Yellow Ginger; Terra Merita; Yellow Root; Safran d'Inde; Yo-Kin; Golden seal; Curcuma oil; Orange Root; Oils, curcuma; CI Natural Yellow 3; Curcumine; Hydrastis; Indian turmeric; Yellow puccoon; Turmeric extract; Diferaloylmethane; Kurkumin [Czech]; (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; Tumeric yellow; Turmeric oil
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MOA Inhibitor
External Link
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
 Compound Name NSC-622444 Investigative [2]
Synonyms
NSC622444; CHEMBL116347; AC1Q3LXD; AC1L7GK5; SCHEMBL9755151; dichlorinated diacylmethane fragment; ZINC1616868; BDBM50048522; 5,3'-dicarboxy-4,4'-dihydrodiphenylmethane; 5,5''-methylenebis(3-chloro-2-hydroxybenzoic acid); 5,5'-Methylenebis(3-chloro-2-hydroxybenzoic acid); 3,3'-methanediylbis(5-chloro-6-hydroxybenzoic acid); 5-(3-carboxy-5-chloro-4-hydroxybenzyl)-3-chloro-2-hydroxybenzoic acid; 3',3-Dichloro-4',4-dimethoxy-5',5-bis(methoxycarbonyl)-1,1-diphenylmethane
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MOA Inhibitor
External Link
 Compound Name NSC-138419 Investigative [2]
Synonyms
NSC138419; n-[4-(methylamino)benzoyl]glutamic acid; AC1Q5SG8; AC1L5YW4; SCHEMBL5925511; CHEMBL591443; CTK1H0013; 2-[(4-methylaminobenzoyl)amino]pentanedioic acid; A816490; 2-[[4-(methylamino)benzoyl]amino]pentanedioic acid; 2-[[4-(methylamino)phenyl]carbonylamino]pentanedioic acid; 2-[[[4-(methylamino)phenyl]-oxomethyl]amino]pentanedioic acid
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MOA Inhibitor
External Link
 Compound Name NSC-319745 Investigative [2]
Synonyms
61629-60-5; HB 093; BRN 2168571; 4-(2-((5-Chloro-2-methoxybenzoyl)amino)ethyl)hydrocinnamic acid; 3-[4-[2-[(5-CHLORO-2-METHOXY-BENZOYL)AMINO]ETHYL]PHENYL]PROPANOIC ACID; 3-(4-(2-(5-Chlor-2-methoxy-benzamido)-aethyl)phenyl)-propionsaeure [German]; 3-[4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]phenyl]propanoic acid; HYDROCINNAMIC ACID, 4-(2-((5-CHLORO-2-METHOXYBENZOYL)AMINO)ETHYL)-; AC1L2AFL; CHEMBL597112; SCHEMBL11481071; CTK5B3505; DTXSID00210642; AIEFQKOARQRACO-UHFFFAOYSA-N; ZINC1572211; HB-093; NSC319745
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MOA Inhibitor
External Link
 Compound Name NSC-348926 Investigative [2]
Synonyms
NSC348926; 2-phthalimidoadipic acid; AC1L7IP1; SCHEMBL9741723; CHEMBL599367; 2-(1,3-dioxoisoindol-2-yl)hexanedioic acid
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MOA Inhibitor
External Link
 Compound Name NSC-401077 Investigative [2]
Synonyms
NSC401077; MLS000757170; DNA Methyltransferase Inhibitor; CHEMBL383475; 32675-71-1; 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(1H-indol-3-yl)-propionic acid; 2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propionic acid; SMR000413613; AC1Q71QA; Oprea1_475901; Oprea1_410805; MLS000777218; MLS006011919; SCHEMBL562060
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MOA Inhibitor
External Link
 Compound Name S-tubercidinylhomocysteine Investigative [4]
Synonyms
CHEMBL552309; 57344-98-6; AC1L3YAS; AC1Q5QMO; (S)-7-(5-S-(3-amino-3-carboxypropyl)-5-thio-beta-D-ribofuranosyl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine; (2s)-2-amino-4-({[(2s,3s,4r,5r)-5-(4-amino-7h-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)butanoic acid(non-preferred name); BDBM50294482; (2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid
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MOA Inhibitor
Activity IC50 = 300 nM
External Link
 Compound Name NSC-106084 Investigative [2]
Synonyms
CHEMBL597113; NSC106084; AC1L6H8Q; CTK7J5419; ZINC1868549; BDBM50308983; {4-[5-bromo-2-(carboxymethoxy)benzoyl]phenoxy}acetic acid; 2-(4-bromo-2-(4-(carboxymethoxy)benzoyl)phenoxy)acetic acid; 2-[4-[5-bromo-2-(carboxymethyloxy)benzoyl]phenoxy]acetic acid
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MOA Inhibitor
External Link
 Compound Name NSC-154957 Investigative [2]
Synonyms
NSC154957; AC1L6EF2; CHEMBL586418; 3-benzhydrylsulfanyl-2-formamidopropanoic acid
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MOA Inhibitor
External Link
 Compound Name NSC-54162 Investigative [2]
Synonyms
NSC54162; AC1Q5WTA; AC1L6CM2; CHEMBL611994; 2,2'-{[(2-hydroxyphenyl)methanediyl]disulfanediyl}diacetic acid; ZINC1685025; Acetic acid, (salicylidenedithio)di-; 4265-51-4; Acetic acid, [(o-hydroxybenzylidene)dithio]di-; Acetic acid,2'-[[(2-hydroxyphenyl)methylene]bis(thio)]bis-; 2-[carboxymethylsulfanyl-(2-hydroxyphenyl)methyl]sulfanylacetic acid
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MOA Inhibitor
External Link
 Compound Name NSC-57893 Investigative [2]
Synonyms
MLS002667915; 7399-94-2; 4-[(1h-benzimidazol-2-ylmethyl)(formyl)amino]benzoic acid; NSC57893; AC1L6GFK; AC1Q5TWY; NCIOpen2_002368; CHEMBL599366; 4-[1H-benzimidazol-2-ylmethyl(formyl)amino]benzoic acid; CTK5D9099; DTXSID30288854; HMS3089M13; ZINC1688755; AKOS030547711
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MOA Inhibitor
External Link
 Compound Name NSC-56071 Investigative [2]
Synonyms
32230-52-7; NSC56071; AC1L6EJV; AC1Q7ES0; NCIOpen2_007380; CHEMBL596910; CTK4G8394; DTXSID80288485; ZINC1686711; 2,2'-[piperazine-1,4-diylbis(carbonothioylsulfanediyl)]diacetic acid; AKOS030574801; Acetic acid,2,2'-[1,4-piperazinediylbis(carbonothioylthio)]bis- (9CI); 2-[4-(carboxymethylsulfanylcarbothioyl)piperazine-1-carbothioyl]sulfanylacetic acid
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MOA Inhibitor
External Link
 Compound Name NSC-137546 Investigative [2]
Synonyms
NSC137546; CHEMBL591202; AC1L5Y49; AKOS008984447; 2-[(2,6-dichlorobenzoyl)amino]pentanedioic acid
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MOA Inhibitor
External Link
 Compound Name NSC-623548 Investigative [2]
Synonyms
2581-36-4; NSC 408488; o-Cresotic acid, 5,5'-methylenedi-; 2,3-CRESOTIC ACID, 5,5'-METHYLENEDI-; UNII-S3D8KC88KC; 5,5'-Methylenedi-2,3-cresotic acid; NSC 623548; BRN 3433298; S3D8KC88KC; CHEMBL113835; 5,5'-Methylenedi-o-cresotic acid; NSC623548; NSC408488; 5,5'-Methylenebis(2-hydroxy-3-methylbenzoic acid); 2, 5,5'-methylenedi-; AC1L29YK; Oprea1_231968; 2-10-00-00398 (Beilstein Handbook Reference); SCHEMBL9755153; CTK4F6504; DTXSID90180466; o-Cresotic acid,5'-methylenedi-; MolPort-000-698-522; ZINC4028795; STL511095
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MOA Inhibitor
External Link
 Compound Name NSC-345763 Investigative [2]
Synonyms
7-(8-hydroxyquinolin-5-yl)-4,7-dioxoheptanoic acid; NSC345763; AC1L7HSU; CHEMBL597114
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MOA Inhibitor
External Link
 Compound Name NSC-158324 Investigative [2]
Synonyms
Acediasulfone; UNII-30YP2YHH8W; 30YP2YHH8W; CHEMBL48396; N-[4-[(4-AMINOPHENYL)SULPHONYL]PHENYL]GLYCINE; 2-[4-(4-aminophenyl)sulfonylanilino]acetic acid; Acediasulfonum; N-(4-((4-Aminophenyl)sulphonyl)phenyl)glycine; EINECS 201-243-7; AC1L25EF; ZINC862; SCHEMBL143660; CTK5E7379; DTXSID00229991; CHEBI:135300; BDBM50099670; AKOS027327086; DB08926; Glycine,N-[4-[(4-aminophenyl)sulfonyl]phenyl]-; {4-[(4-aminophenyl)sulfonyl]anilino}acetic acid; 2-(4-(4-aminophenylsulfonyl)phenylamino)acetic acid
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MOA Inhibitor
External Link
 Compound Name (L-)-S-adenosyl-L-homocysteine Investigative [5]
Synonyms
S-Adenosyl-L-homocysteine; S-adenosylhomocysteine; 979-92-0; AdoHcy; S-(5'-adenosyl)-L-homocysteine; adenosylhomocysteine; Formycinylhomocysteine; Adenosyl-L-homocysteine; S-(5'-deoxyadenosin-5'-yl)-L-homocysteine; 2-S-adenosyl-L-homocysteine; 5'-Deoxy-S-adenosyl-L-homocysteine; S-adenosyl-homocysteine; S-Adenosyl Homocysteine; L-S-Adenosylhomocysteine; L-Homocysteine, S-(5'-deoxyadenosin-5'-yl)-; adenosylhomo-cys; adenosyl-homo-cys; UNII-8K31Q2S66S; (S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine; BRN 5166233; SAH
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MOA Inhibitor
Activity IC50 = 200 nM
External Link
 Compound Name NSC-622445 Investigative [2]
Synonyms
5,5'-Methylenedisalicylic acid; 122-25-8; 5,5'-Methylenebis(2-hydroxybenzoic acid); Methylenebis(salicylic acid); 5,5-Methylenebis(salicylic acid); UNII-2KF4FVV76N; 5,5-Methylenedisalicylic acid; 5-(3-Carboxy-4-hydroxybenzyl)salicylic acid; 4,4'-Dihydroxy-3,3'-dicarboxydiphenylmethane; 3,3'-Dicarboxy-4,4'-dihydroxydiphenylmethane; NSC 14778; 2KF4FVV76N; 4,4'-Dihydroxydiphenylmethane-3,3'-dicarboxylic acid; 3,3'-Methylenebis(6-hydroxybenzoic acid); CHEMBL115145; Benzoic acid, 3,3'-methylenebis[6-hydroxy-
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MOA Inhibitor
Activity IC50 = 17000 nM
External Link
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [6]
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
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External Link
 Compound Name Everolimus Approved [7]
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References
Ref 1 LncRNA UCA1 promotes SOX12 expression in breast cancer by regulating m(6)A modification of miR-375 by METTL14 through DNA methylation. Cancer Gene Ther. 2022 Jul;29(7):1043-1055. doi: 10.1038/s41417-021-00390-w. Epub 2022 Jan 13.
Ref 2 Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9. doi: 10.1016/j.bmc.2009.11.050. Epub 2009 Nov 27.
Ref 3 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 4 SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes. Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28.
Ref 5 Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
Ref 6 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 7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015