m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03078
 [1]
m6A modification ACSS3 ACSS3 METTL3 Methylation : m6A sites Indirect Enhancement Histone modification H3k23pr Regulated Regulator ACACB
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Regulated Target Histone H3 lysine 23 propionylation (H3k23pr) View Details
Downstream Gene ACACB View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification indirectly regulates histone modification through downstream signaling pathways
Crosstalk Summary RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (Acyl-CoA synthetase short-chain family member 3, mitochondrial (ACSS3)), which generates propionyl-CoA to upregulate lipid metabolism genes (ACACB, Fasn, Me1, Mid1ip1) via Histone H3 lysine 23 propionylation (H3k23pr). The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD.
Responsed Disease Nonalcoholic fatty liver disease ICD-11: DB92.Z
 Disease Info 
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]
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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 Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11. Cell Metab. 2024 Oct 1;36(10):2228-2244.e7. doi: 10.1016/j.cmet.2024.07.014. Epub 2024 Aug 14.
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.