m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03135
 [1]
Histone modification H3K18lac LDHA METTL3 Indirect Enhancement m6A modification SCD SCD YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
m6A Target Stearoyl-CoA desaturase (SCD)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lactate dehydrogenase A (LDHA) WRITER View Details
Regulated Target Histone H3 lysine 18 lactylation (H3K18lac) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary LDHA-induced Histone H3 lysine 18 lactylation (H3K18lac) promoted NAFLD progression, where LDHA-induced H3K18lac in METTL3 promoter elevated METTL3 expression, thereby promoting m6A methylation and stabilizing Stearoyl-CoA desaturase (SCD) via a YTHDF1-dependent manner. Keywords: Nonalcoholic fatty liver disease, LDHA, METTL3, YTHDF1, Histone lactylation.
Responsed Disease Nonalcoholic fatty liver disease ICD-11: DB92.Z
 Disease Info 
In-vitro Model
 L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Lactate dehydrogenase A (LDHA) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Nedosiran Approved [2]
Synonyms
nedosiran
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TTD: DZ8DF0
DB92: Non-alcoholic fatty liver disease 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Epeleuton Phase 2 [3]
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 [4]
External Link
TTD: DMN03O
 Compound Name TVB-2640 Phase 2 [5]
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 [6]
Synonyms
IONIS-ANGPTL3-LRx; AKCEA-ANGPTL3-LRx
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TTD: DDU2Y0
 Compound Name ZED1227 Phase 2 [7]
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 [8]
External Link
TTD: D67AKN
 Compound Name ASP9831 Phase 2 [9]
External Link
TTD: D5ON9Z
 Compound Name Netoglitazone Phase 2 [10]
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 [11]
Synonyms
AZD4076
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External Link
TTD: D0U0SD
 Compound Name GSK-677954 Discontinued in Phase 2 [12]
Synonyms
SCHEMBL2065429
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External Link
CID: 56603715
TTD: D0S6KX
 Compound Name KD-3020 Preclinical [12]
External Link
TTD: D06GFG
 Compound Name RIPA-56 Investigative [13]
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 LDHA- Mediated Histone Lactylation Promotes the Nonalcoholic Fatty Liver Disease Progression Through Targeting The METTL3/ YTHDF1/SCD1 m6A Axis. Physiol Res. 2024 Dec 31;73(6):985-999. doi: 10.33549/physiolres.935289.
Ref 2 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.
Ref 3 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 4 ClinicalTrials.gov (NCT02316717) A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis. U.S. National Institutes of Health.
Ref 5 ClinicalTrials.gov (NCT03938246) Study of TVB 2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH). U.S. National Institutes of Health.
Ref 6 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 7 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 8 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 9 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 10 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 11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 12 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 13 Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease. J Hepatol. 2020 Apr;72(4):627-635.