m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00528
 [1], [2], [3]
m6A modification HIF1A HIF1A METTL3 Methylation : m6A sites Indirect Inhibition RNA modification MIR576 MIR576 FTO Demethylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N6,2'-O-dimethyladenosine (m6Am)
Epigenetic Regulator Fat mass and obesity-associated protein (FTO) ERASER View Details
Regulated Target MicroRNA 576 (MIR576) View Details
Crosstalk Relationship m6Am  →  m6A Inhibition
Crosstalk Mechanism RNA modification indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary FTO interacts with MicroRNA 576 (MIR576), decreasing it's m6Am level and inhibiting 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
T24 Bladder carcinoma Homo sapiens CVCL_0554
UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
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
CID: 91754484
TTD: D0C9PZ
 Compound Name ISIS 298697 Investigative [5]
External Link
TTD: D00JHE
 Compound Name ISIS 298744 Investigative [5]
External Link
TTD: D01DDQ
 Compound Name ISIS 298746 Investigative [5]
External Link
TTD: D01ZCK
 Compound Name ISIS 298745 Investigative [5]
External Link
TTD: D07GVC
 Compound Name ISIS 298743 Investigative [5]
External Link
TTD: D09DCJ
 Compound Name ISIS 298702 Investigative [5]
External Link
TTD: D0B5LQ
 Compound Name ISIS 298700 Investigative [5]
External Link
TTD: D0C2IG
 Compound Name ISIS 175510 Investigative [5]
External Link
TTD: D0G9BP
 Compound Name ISIS 298699 Investigative [5]
External Link
TTD: D0L5ME
 Compound Name ISIS 298712 Investigative [5]
External Link
TTD: D0L9KW
 Compound Name ISIS 298711 Investigative [5]
External Link
TTD: D0SN5O
 Compound Name ISIS 298701 Investigative [5]
External Link
TTD: D0X8GB
 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
CID: 5712
TTD: D00REK
 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
CID: 5328127
TTD: D0B0AX
 Compound Name IT-101 Phase 3 [7]
External Link
TTD: D06PEW
 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
CID: 66414
TTD: D06NYA
DrugBank: DB02342
 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
CID: 11234794
TTD: D06ZVO
DrugBank: DB06082
 Compound Name EZN-2968 Phase 1 [7]
External Link
TTD: D0NF5J
 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
CID: 11483754
TTD: D0Y5QD
DrugBank: DB05959
 Compound Name Pyrrolidine carboxamide derivative 1 Patented [7]
Synonyms
PMID26882240-Compound-22
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External Link
CID: 56684144
TTD: D0Q2SE
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 FTO promotes tumour proliferation in bladder cancer via the FTO/miR-576/CDK6 axis in an m6A-dependent manner. Cell Death Discov. 2021 Nov 1;7(1):329. doi: 10.1038/s41420-021-00724-5.
Ref 3 MicroRNA?576?3p inhibits the migration and proangiogenic abilities of hypoxia?treated glioma cells through hypoxia?inducible factor?1alpha. Int J Mol Med. 2019 Jun;43(6):2387-2397. doi: 10.3892/ijmm.2019.4157. Epub 2019 Apr 4.
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.