m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02213
 [1], [2]
DNA methylation DNMT3B METTL14 Direct Inhibition m6A modification FPN1 FPN1 METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target Solute carrier family 40 member 1 (FPN1)
 Targert Gene 
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. m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-SLC7A11/Solute carrier family 40 member 1 (FPN1) signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Pertuzumab
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model
 MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
SUM159PT Breast pleomorphic carcinoma Homo sapiens CVCL_5423
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
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 [3]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 969516
TTD: D07SDQ
DrugBank: DB11672
 Compound Name PMID27376512-Compound-MTC-424 Patented [4]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [4]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [4]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [4]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
 Compound Name NSC-622444 Investigative [3]
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
CID: 360384
TTD: D01VNN
 Compound Name NSC-138419 Investigative [3]
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
CID: 283555
TTD: D03PWU
 Compound Name NSC-319745 Investigative [3]
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
CID: 43709
TTD: D06RGX
 Compound Name NSC-348926 Investigative [3]
Synonyms
NSC348926; 2-phthalimidoadipic acid; AC1L7IP1; SCHEMBL9741723; CHEMBL599367; 2-(1,3-dioxoisoindol-2-yl)hexanedioic acid
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 336008
TTD: D06VVV
 Compound Name NSC-401077 Investigative [3]
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
CID: 344265
TTD: D07VWC
 Compound Name S-tubercidinylhomocysteine Investigative [5]
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
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 300 nM
External Link
CID: 124349
TTD: D08TGQ
 Compound Name NSC-106084 Investigative [3]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 266989
TTD: D0A2ZH
 Compound Name NSC-154957 Investigative [3]
Synonyms
NSC154957; AC1L6EF2; CHEMBL586418; 3-benzhydrylsulfanyl-2-formamidopropanoic acid
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MOA Inhibitor
External Link
CID: 290753
TTD: D0C4NA
 Compound Name NSC-54162 Investigative [3]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 243918
TTD: D0FN7C
 Compound Name NSC-57893 Investigative [3]
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
CID: 245689
TTD: D0G9NS
 Compound Name NSC-56071 Investigative [3]
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
CID: 244824
TTD: D0H1YK
 Compound Name NSC-137546 Investigative [3]
Synonyms
NSC137546; CHEMBL591202; AC1L5Y49; AKOS008984447; 2-[(2,6-dichlorobenzoyl)amino]pentanedioic acid
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MOA Inhibitor
External Link
CID: 283188
TTD: D0I5JP
 Compound Name NSC-623548 Investigative [3]
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
CID: 17413
TTD: D0LS2U
 Compound Name NSC-345763 Investigative [3]
Synonyms
7-(8-hydroxyquinolin-5-yl)-4,7-dioxoheptanoic acid; NSC345763; AC1L7HSU; CHEMBL597114
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MOA Inhibitor
External Link
CID: 335596
TTD: D0MP7N
 Compound Name NSC-158324 Investigative [3]
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
CID: 24193827
TTD: D0W5SZ
 Compound Name (L-)-S-adenosyl-L-homocysteine Investigative [6]
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
CID: 439155
TTD: D09CLP
DrugBank: DB01752
 Compound Name NSC-622445 Investigative [3]
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
CID: 67145
TTD: D0J5VK
Solute carrier family 40 member 1 (FPN1) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name LY2928057 Phase 2 [7]
MOA Modulator
External Link
TTD: D0IN8Z
 Compound Name Ferroportin mab Phase 1 [8]
External Link
TTD: D07SQT
 Compound Name M012 Phase 1 [9]
Synonyms
Benzal chloride; 98-87-3; (DICHLOROMETHYL)BENZENE; alpha,alpha-Dichlorotoluene; Benzylidene chloride; Benzene, (dichloromethyl)-; Benzyl dichloride; Dichloromethylbenzene; Benzylene chloride; Chlorobenzal; Dichlorophenylmethane; DICHLOROTOLUENE; Chlorure de benzylidene; Benzene, dichloromethyl-; RCRA waste number U017; NSC 7915; Benzylidene dichloride; UNII-222447TR16; 29797-40-8; CHEBI:82273; Toluene, .alpha.,.alpha.-dichloro-; 222447TR16; DSSTox_CID_5014; DSSTox_RID_77628; DSSTox_GSID_25014; CAS-98-87-3; CCRIS 959; Toluene, alpha,alpha-dichloro-; Cloruro de bencilideno; Chlorure de benzylidene [French]; Cloruro de bencilideno [Spanish]; HSDB 5322; EINECS 202-709-2; UN1886; RCRA waste no. U017; benzalchlorid; BRN 1099407; AI3-28597; chlorobenzyl chloride; EINECS 249-854-8; Benzal chloride???; WLN: GYGR; 1-(dichloromethyl)benzene; alpha-alpha-Dichlorotoluene; EC 202-709-2; EC 249-854-8; SCHEMBL28353; 4-05-00-00817 (Beilstein Handbook Reference); alpha,alpha-Dichlortoluene; CHEMBL1412576; DTXSID6025014; Cl[C](Cl)C1=CC=CC=C1; NSC7915; alpha,alpha-Dichlorotoluene, 95%; ALPHA,ALPHA-DICHLORO-TOLUENE; NSC-7915; ZINC1586312; Tox21_201313; Tox21_300171; MFCD00000829; AKOS015902605; FS-4304; MCULE-5551252494; Toluene, alpha,alpha-dichloro- (8CI); UN 1886; NCGC00091362-01; NCGC00091362-02; NCGC00091362-03; NCGC00254144-01; NCGC00258865-01; Benzylidene chloride [UN1886] [Poison]; FT-0694812; C19165; Q419420; alpha,alpha-Dichlorotoluene, PESTANAL(R), analytical standard
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MOA Agonist
External Link
CID: 7411
TTD: D5W7BG
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [10]
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
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [11]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
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 N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 3 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 4 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 5 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 6 Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
Ref 7 Targeting the Hepcidin-Ferroportin Axis to Develop New Treatment Strategies for Anemia of Chronic Disease and Anemia of Inflammation. Am J Hematol. 2012 April; 87(4): 392-400.
Ref 8 The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. 2014 March; 35(3): 155-161.
Ref 9 Hepcidin agonists as therapeutic tools. Blood. 2018 Apr 19;131(16):1790-1794. doi: 10.1182/blood-2017-11-737411. Epub 2018 Mar 9.
Ref 10 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 11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015