Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00524
[1], [2], [3]
RNA modification MIR142 MIR142 ADARB1 Methylation : modification sites Indirect Enhancement m6A modification HIF1A HIF1A METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> Adenosine-to-Inosine editing (A-to-I)
Epigenetic Regulator Double-stranded RNA-specific editase 1 (ADARB1) WRITER View Details
Regulated Target MicroRNA 142 (MIR142) View Details
Crosstalk Relationship A-to-I  →  m6A Enhancement
Crosstalk Mechanism RNA modification indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary ADARB1 interacts with MicroRNA 142 (MIR142), increasing it's A-to-I level and promoting its physical interaction with Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A), which was regulated by METTL3-mediated m6A modification.
In-vitro Model
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
MHCC97 Adult hepatocellular carcinoma Homo sapiens CVCL_4971
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) 21 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PT2385 Phase 2 [4]
Synonyms
ONBSHRSJOPSEGS-INIZCTEOSA-N; PT-2385; UNII-6O16716DXP; 1672665-49-4; 6O16716DXP; SCHEMBL16555810; ZINC230453533; AKOS030526641; HY-12867; PT2385,1672665-49-4, PT 2385,PT-2385; Benzonitrile, 3-(((1S)-2,2-difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl)oxy)-5-fluoro-; 3-{[(1s)-2,2-Difluoro-1-Hydroxy-7-(Methylsulfonyl)-2,3-Dihydro-1h-Inden-4-Yl]oxy}-5-Fluorobenzonitrile; 3-(((1S)-2,2-Difluoro-1-hydroxy-7-methanesulfonyl-2,3-dihydro-1hinden-4-yl)oxy)-5-fluorobenzonitrile; 79A
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MOA Inhibitor
External Link
 Compound Name ISIS 298697 Investigative [5]
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 Compound Name ISIS 298744 Investigative [5]
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 Compound Name ISIS 298746 Investigative [5]
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 Compound Name ISIS 298745 Investigative [5]
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 Compound Name ISIS 298743 Investigative [5]
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 Compound Name ISIS 298702 Investigative [5]
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 Compound Name ISIS 298700 Investigative [5]
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 Compound Name ISIS 175510 Investigative [5]
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 Compound Name ISIS 298699 Investigative [5]
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 Compound Name ISIS 298712 Investigative [5]
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 Compound Name ISIS 298711 Investigative [5]
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 Compound Name ISIS 298701 Investigative [5]
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 Compound Name (5-(1-benzyl-1H-indazol-3-yl)furan-2-yl)methanol Investigative [6]
Synonyms
Lificiguat; yc-1; 170632-47-0; 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole; YC 1; UNII-515CC1WPTE; Lificiguat(YC-1); 154453-18-6; [5-(1-benzyl-1h-indazol-3-yl)-2-furyl]methanol; 515CC1WPTE; CHEMBL333985; OQQVFCKUDYMWGV-UHFFFAOYSA-N; C19H16N2O2; 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole; 1-Benzyl-3-(5-hydroxymethyl-2-furyl)indazole; [5-(1-benzyl-1H-indazol-3-yl)furan-2-yl]methanol; 5-[1-(Phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol
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MOA Inhibitor
External Link
 Compound Name HIF-1alpha Phase 4 [7]
Synonyms
Unii-NA856793UT; 192705-79-6; PD-166866; PD166866; PD 166866; CHEMBL299763; NA856793UT; 1-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea; 1-(2-Amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl)-3-tert-butyl urea; Urea,N-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)-; 1-[2-Amino-6-(3,5-dimethoxyphenyl)-pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butyl urea; 6-arylpyrido[2,3-d]pyrimidine deriv 25; AC1NS3U5; SCHEMBL1248489; BDBM3443; CTK4E1060
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External Link
 Compound Name IT-101 Phase 3 [7]
External Link
 Compound Name 2-Methoxyestradiol Phase 2 [7]
Synonyms
ESM; Panzem; PulmoLAR; Panzem NCD; M 6383; (17beta)-2-Methoxyestra-1,3,5(10)-triene-3,17-diol; (17beta)-2-methoxyestra-1(10),2,4-triene-3,17-diol; (8R,9S,13S,14S,17S)-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; 1,3,5(10)-ESTRATRIEN-2,3,17-BETA-TRIOL 2-METHYL ETHER; 1,3,5(10)-Estratriene-2,3,17-triol 2-methyl ether; 2,3,17beta-Trihydroxy-1,3,5(10)-estratriene 2-methyl ether; 2-Hydroxyestradiol 2-methyl ether; 2-Hydroxyestradol 2-methyl ether; 2-ME2, 2-Methoxyestradiol; 2-Methoxyestra-1,3,5(10)-triene-3,17beta-diol; 2-Methoxyestradiol-17beta; 3,17beta-Dihydroxy-2-methoxy-1,3,5(10)-estratriene
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External Link
 Compound Name PX-478 Phase 1 [7]
Synonyms
685898-44-6; PX-478 2HCl; UNII-T23U22X160; PX478; PX 478; Melphalan N-Oxide Impurity HCl; T23U22X160; 4-[Bis(2-chloroethyl)oxidoamino]-L-phenylalanine; PX-478 dihydrochloride; SCHEMBL18548830; C13H18Cl2N2O3.2ClH; DTXSID00218688; MolPort-035-789-733; 2675AH; s7612; 2-Amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide; AKOS030231369; CS-5164; HY-10231; KB-80169; Z-3209; L-Phenylalanine, 4-(bis(2-chloroethyl)oxidoamino)-, dihydrochloride; (S)-4-(2-amino-2-carboxyethyl)-N,N-bis(2-chloroethyl)aniline oxide di
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External Link
 Compound Name EZN-2968 Phase 1 [7]
External Link
 Compound Name ENMD-1198 Phase 1 [7]
Synonyms
EM-5171; EM-883; EM-900; Hypoxia inducible factor 1 inhibitors, EntreMed; HIF-1 inhibitors, EntreMed; HIF-1 inhibitors (cancer), EntreMed; 2-ME2 analogs (oral, cancer), EntreMed; 2-methoxyestradiol analogs (oral, cancer), EntreMed
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External Link
 Compound Name Pyrrolidine carboxamide derivative 1 Patented [7]
Synonyms
PMID26882240-Compound-22
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References
Ref 1 HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1Alpha. J Cell Physiol. 2021 May;236(5):3863-3880. doi: 10.1002/jcp.30128. Epub 2020 Dec 11.
Ref 2 Lipopolysaccharide enhances ADAR2 which drives Hirschsprung's disease by impairing miR-142-3p biogenesis. J Cell Mol Med. 2018 Sep;22(9):4045-4055. doi: 10.1111/jcmm.13652. Epub 2018 Jun 29.
Ref 3 GSK343, an inhibitor of EZH2, mitigates fibrosis and inflammation mediated by HIF-1alpha in human peritoneal mesothelial cells treated with high glucose. Eur J Pharmacol. 2020 Aug 5;880:173076. doi: 10.1016/j.ejphar.2020.173076. Epub 2020 Mar 25.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 US patent application no. 7,217,572, Modulation of HIF1.alpha. and HIF2.alpha. expression.
Ref 6 Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6305-10. doi: 10.1016/j.bmcl.2007.09.005. Epub 2007 Sep 7.
Ref 7 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.