m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03164
 [1]
m6A modification Circ_SLC9A6 Circ_SLC9A6 YTHDF2 : m6A sites Indirect Inhibition Histone modification H4K16ac MOF CD36
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Circ_SLC9A6
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase KAT8 (KAT8) WRITER View Details
Regulated Target Histone H4 lysine 16 acetylation (H4K16ac) View Details
Downstream Gene CD36 View Details
Crosstalk Relationship m6A  →  Histone modification Inhibition
Crosstalk Mechanism m6A modification indirectly regulates histone modification through downstream signaling pathways
Crosstalk Summary YTHDF2-mediated degradation of m6A-modified Circ_SLC9A6 was found to be essential for the regulation of SLC9A6-126aa expression. Nuclear SLC9A6-126aa promotes transcriptional activation of the target gene CD36 and enhances its occupancy of the CD36 promoter locus by regulating KAT8-mediated histone Histone H4 lysine 16 acetylation (H4K16ac).
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]
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 A novel peptide encoded by circ-SLC9A6 promotes lipid dyshomeostasis through the regulation of H4K16ac-mediated CD36 transcription in NAFLD. Clin Transl Med. 2024 Aug;14(8):e1801. doi: 10.1002/ctm2.1801.
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.