m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02110
 [1]
DNA methylation Epigenetic Regulator ALKBH5 Direct Inhibition m6A modification ATG12 ATG12 ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target Ubiquitin-like protein ATG12 (ATG12)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Regulated Target RNA demethylase ALKBH5 (ALKBH5) 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 Folic acid reduces the expression of ALKHB5 via promoter DNA hypermethylation. Decreased ALKBH5 causes increased m6A modification and increased expression of Ubiquitin-like protein ATG12 (ATG12) in a demethylase activity-dependent manner, thereby promoting autophagy and preventing hepatic steatosis.
Responsed Disease Nonalcoholic fatty liver disease ICD-11: DB92.Z
 Disease Info 
Cell Process Cell autophagy
Lipid metabolism
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DB92: Non-alcoholic fatty liver disease 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Epeleuton Phase 2 [2]
Synonyms
(S,5Z,8Z,11Z,13E,17Z)-Ethyl 15-hydroxyicosa-5,8,11,13,17-pentaenoate; 15(S)-HEPE-EE; 15(S)-HYDROXY-(5Z,8Z,11Z,13E,17Z)-EICOSAPENTAENOIC ACID ETHYL ESTER; 1667760-39-5; 5,8,11,13,17-Eicosapentaenoic acid, 15-hydroxy-, ethyl ester, (5Z,8Z,11Z,13E,15S,17Z)-; AKOS040748327; CHEMBL5095178; Epeleuton; Epeleuton [INN]; FA9BPX1T6V; UNII-FA9BPX1T6V
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CID: 133082733
TTD: DV8F9L
 Compound Name IMM-124E Phase 2 [3]
External Link
TTD: DMN03O
 Compound Name TVB-2640 Phase 2 [4]
Synonyms
FASN-IN-2; 1399177-37-7; 4-(1-(4-Cyclobutyl-2-methyl-5-(5-methyl-4H-1,2,4-triazol-3- yl)benzoyl)piperidin-4-yl)benzonitrile; US8871790, 480; CHEMBL3661754; SCHEMBL12488853; BDBM137084; BCP30428; EX-A3643; s9714; ZINC150188638; HY-112829; CS-0066310; TVB2640; TVB 2640;FASN-IN-2; US8871790, 152; 4-(1-(4-Cyclobutyl-2-methyl-5-(3-methyl-1H-1,2,4-triazol-5-yl)benzoyl)piperidin-4-yl)benzonitrile; 4-(1-(4-cyclobutyl-2-methyl-5-(5-methyl-4H-1,2,4-triazol-3-yl)benzoyl)piperidin-4-yl)benzonitrile; 4-[1-[4-cyclobutyl-2-methyl-5-(5-methyl-1H-1,2,4-triazol-3-yl)benzoyl]piperidin-4-yl]benzonitrile
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CID: 66548316
TTD: DE2U5N
 Compound Name Vupanorsen Phase 2 [5]
Synonyms
IONIS-ANGPTL3-LRx; AKCEA-ANGPTL3-LRx
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TTD: DDU2Y0
 Compound Name ZED1227 Phase 2 [6]
Synonyms
(2E,6S)-7-((1-(2-((2-Ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1H-imidazol-5-yl)carbonyl)amino)-7-oxo-2-heptenoic acid methyl ester; (2E,6S)-7-[[1-[2-[(2-Ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1H-imidazol-5-yl)carbonyl]amino]-7-oxo-2-heptenoic Acid Methyl Ester; 1542132-88-6; 2-Heptenoic acid, 7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1H-imidazol-5-yl)carbonyl)amino)-7-oxo-, methyl ester, (2E,6S)-; 2-Heptenoic acid, 7-[[1-[2-[(2-ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1H-imidazol-5-yl)carbonyl]amino]-7-oxo-, methyl ester, (2E,6S)-; AKOS040742843; BDBM50245478; CHEMBL4081588; CS-0015432; EX-A7845R; GLUTAMINASE; GTPL12802; HY-19359; Methyl (2E,6S)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1H-imidazol-5-yl)carbonyl)amino)-7-oxo-2-heptenoate; Methyl (2E,6S)-7-[[1-[2-[(2-ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1H-imidazol-5-yl)carbonyl]amino]-7-oxo-2-heptenoate; Methyl (E,6S)-7-((1-(2-(2-ethylbutylamino)-2-oxo-ethyl)-2-oxo-3-pyridyl)amino)-6-((3-methylimidazole-4-carbonyl)amino)-7-oxo-hept-2-enoate; methyl (E,6S)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxopyridin-3-yl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate; methyl (S,E)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl)amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate; MS-29784; SCHEMBL16735736; SCHEMBL16751074; T4SR539YKF; TAK-227; UNII-T4SR539YKF; ZED1227; ZED-1227
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CID: 72950407
TTD: DB2V8K
 Compound Name PXL-770 Phase 2 [7]
External Link
TTD: D67AKN
 Compound Name ASP9831 Phase 2 [8]
External Link
TTD: D5ON9Z
 Compound Name Netoglitazone Phase 2 [9]
Synonyms
Isaglitazone; Netoglitazone [USAN]; MCC 555; MCC-555; RWJ-241947; Netoglitazone (USAN/INN); 5-((6-((2-fluorophenyl)methoxy)-2-naphthalenyl)methyl)-2,4-thiazolidinedione; 5-({6-[(2-fluorobenzyl)oxy]naphthalen-2-yl}methyl)-1,3-thiazolidine-2,4-dione; 5-[[6-[(2-fluorophenyl)methoxy]naphthalen-2-yl]methyl]-1,3-thiazolidine-2,4-dione
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CID: 204109
TTD: D02TGD
DrugBank: DB09199
 Compound Name RG-125 Phase 1 [10]
Synonyms
AZD4076
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TTD: D0U0SD
 Compound Name GSK-677954 Discontinued in Phase 2 [11]
Synonyms
SCHEMBL2065429
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CID: 56603715
TTD: D0S6KX
 Compound Name KD-3020 Preclinical [11]
External Link
TTD: D06GFG
 Compound Name RIPA-56 Investigative [12]
Synonyms
1956370-21-0; N-benzyl-N-hydroxy-2,2-dimethylbutanamide; CHEMBL4092421; GTPL9643; SCHEMBL17874088; EX-A4338; BDBM50229025; MFCD30738006; s6511; ZINC616570725; CS-6266; compound 92 [WO2016101885]; compound 56 [PMID: 27992216]; HY-101032; C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O; A1-28956
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CID: 121439991
TTD: DF5C2I
References
Ref 1 DNA hypermethylation-induced suppression of ALKBH5 is required for folic acid to alleviate hepatic lipid deposition by enhancing autophagy in an ATG12-dependent manner. J Nutr Biochem. 2025 Jun;140:109870. doi: 10.1016/j.jnutbio.2025.109870. Epub 2025 Feb 22.
Ref 2 ClinicalTrials.gov (NCT02941549) A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase IIa Study To Assess The Safety And Efficacy Of Orally Administered Epeleuton In NAFLD Patients. U.S.National Institutes of Health.
Ref 3 ClinicalTrials.gov (NCT02316717) A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis. U.S. National Institutes of Health.
Ref 4 ClinicalTrials.gov (NCT03938246) Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH). U.S. National Institutes of Health.
Ref 5 ClinicalTrials.gov (NCT03371355) Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease. U.S. National Institutes of Health.
Ref 6 ClinicalTrials.gov (NCT05305599) Double-blind, Randomized, Placebo-controlled, Phase II Dose-finding Study Comparing Different Doses of ZED1227 Capsules With Placebo in the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD) With Significant Fibrosis. U.S.National Institutes of Health.
Ref 7 ClinicalTrials.gov (NCT03763877) A Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD. U.S. National Institutes of Health.
Ref 8 ClinicalTrials.gov (NCT00668070) A Proof-of-principle Study of Oral Treatment of Non-alcoholic Steatohepatitis With a Novel PDE4 Inhibitor ASP9831. U.S. National Institutes of Health.
Ref 9 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2707).
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):145-58. doi: 10.1517/14728214.13.1.145.
Ref 12 Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease. J Hepatol. 2020 Apr;72(4):627-635.