Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03313
[1], [2]
Histone modification H3K4me3 MLL1 METTL3 Direct Enhancement m6A modification TRAF6 TRAF6 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target TNF receptor-associated factor 6 (TRAF6)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase 2A (KMT2A) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary KMT2A induced rapid Histone H3 lysine 4 trimethylation (H3K4me3) of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. METTL3-mediated m6A modification promotes sympathetic hyperactivity through TNF receptor-associated factor 6 (TRAF6)/ECSIT pathway and mitochondrial oxidative stress in the PVN, thereby leading to ventricular arrhythmias post-MI.
Responsed Disease Acute myocardial infarction ICD-11: BA41
Cell Process Mitochondrial metabolic dysfunction
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
BA41: Acute myocardial infarction 34 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Reteplase Approved [3]
Synonyms
Retevase; Rapilysin (TN); Retavase (TN); Retevase (TN); Reteplase (USAN/INN)
    Click to Show/Hide
External Link
 Compound Name M-enoxaparin Approved [4]
Synonyms
M-enoxaparin (angina)
    Click to Show/Hide
External Link
 Compound Name Anistreplase Approved [5]
External Link
 Compound Name Ridogrel Approved [6]
Synonyms
Ibidel; R-68070; Ridogrel (USAN/INN); 5-[(E)-[pyridin-3-yl-[3-(trifluoromethyl)phenyl]methylidene]amino]oxypentanoic acid
    Click to Show/Hide
External Link
 Compound Name Tisokinase Approved [4]
Synonyms
Plasvata (TN)
    Click to Show/Hide
External Link
 Compound Name Tirofiban Approved [7]
Synonyms
AGG; Aggrastat; Agrastat; Tirofibanum; Aggrastat (TN); Agrastat (TN); L-700462; MK-383; Tirofiban (INN); Tirofiban[BAN:INN]; Tirofiban [INN:BAN]; L-700,462; N-(BUTYLSULFONYL)-O-[4-(4-PIPERIDINYL)BUTYL]-L-TYROSINE; N-(Butylsulfonyl)-O-(4-(4-piperidyl)butyl)-L-tyrosine; N-(butylsulfonyl)-O-(4-piperidin-4-ylbutyl)-L-tyrosine; N-(butylsulfonyl)-o-[4-(piperidin-4-yl)butyl]-l-tyrosine; (2S)-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid
    Click to Show/Hide
External Link
 Compound Name Prasugrel Approved [8]
Synonyms
Effient (TN)
    Click to Show/Hide
External Link
 Compound Name Trapidil Phase 4 [9]
Synonyms
Trapymin; Rocornal; 15421-84-8; Avantrin; Trapymine; N,N-diethyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; AR 12008; Trapidilum [INN-Latin]; UNII-EYG5Y6355E; EINECS 239-434-2; BRN 0186842; 7-Diethylamino-5-methyl-s-triazolo(1,5-a)pyrimidine; MLS000567667; EYG5Y6355E; N,N-Diethyl-5-methyl-(1,2,4)triazolo(1,5-a)pyrimidine-7-amine; (1,2,4)Triazolo(1,5-a)pyrimidin-7-amine, N,N-diethyl-5-methyl-; 5-Methyl-7-diethylamino-s-triazolo-(1,5-a)-pyrimidine; NCGC00016715-01; AR-12008; SMR000154170; SU10991
    Click to Show/Hide
External Link
 Compound Name Entresto Phase 3 [10]
Synonyms
Sacubitril valsartan sodium hydrate; UNII-WB8FT61183; Sacubitril mixture with valsartan; WB8FT61183; Entresto (TN); Valsartan mixture with AHU-377; MolPort-042-624-138; C96H120N12Na6O21; 9052AF; AKOS026670199; ACN-036829; 3-(1-Biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-3'-methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylmethyl)amino)butyrate; AK198922; AC-29037; Sacubitril valsartan sodium hydrate (JAN); FT-0700025; D10226; L-Valine, N-(1-oxopentyl)-N-((2'-(2H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl)-, compd. wi
    Click to Show/Hide
External Link
 Compound Name MultiStem Phase 2 [10]
Synonyms
MultiStem (TN)
    Click to Show/Hide
External Link
 Compound Name Losmapimod Phase 3 [11]
Synonyms
585543-15-3; GSK-AHAB; GW856553; GW856553X; UNII-F2DQF16BXE; F2DQF16BXE; GW-856553; 6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-N-(2,2-dimethylpropyl)pyridine-3-carboxamide; Losmapimod [USAN:INN]; Losmapimod (GW856553X); GSKAHAB; GW 856553X; SB 856553; Losmapimod (USAN/INN); SCHEMBL1070401; GTPL7835; CHEMBL1088752; EX-A486; CHEBI:131167; KKYABQBFGDZVNQ-UHFFFAOYSA-N; MolPort-009-194-138; losmapimod pound> HMS3653G19; BCP09909; AOB87105; ZINC35793138; s7215; BDBM50418610; 2523AH; AKOS015994587
    Click to Show/Hide
External Link
 Compound Name Bendavia Phase 2 [12]
Synonyms
Elamipretide
    Click to Show/Hide
External Link
 Compound Name Dalcetrapib Phase 3 [10]
Synonyms
JTT 705; JTT-705; R-1658; RG-1658; RO-4607381; S-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methylpropanethioate
    Click to Show/Hide
External Link
 Compound Name REG1 Phase 3 [13]
External Link
 Compound Name RGN-352 Phase 2 [10]
Synonyms
Thymosin Beta 4 (injectable)
    Click to Show/Hide
External Link
 Compound Name CSL 112 Phase 2 [14]
External Link
 Compound Name MEDI6012 Phase 1 [15]
Synonyms
RhLCAT; ACP-501
    Click to Show/Hide
External Link
 Compound Name TF0023 Phase 2 [10]
External Link
 Compound Name E5555 Phase 2 [16]
Synonyms
Atopaxar
    Click to Show/Hide
External Link
 Compound Name VT-111a Phase 2 [17]
External Link
 Compound Name RO-4905417 Phase 2 [18]
External Link
 Compound Name Aliskiren/valsartan Phase 2 [19]
Synonyms
Valturna (TN)
    Click to Show/Hide
External Link
 Compound Name M118 Phase 2 [20]
Synonyms
Adomiparin
    Click to Show/Hide
External Link
 Compound Name Ischemic tolerant allogeneic mesenchymal stem cell therapy Phase 2 [21]
External Link
 Compound Name CER-001 Phase 2 [22]
External Link
 Compound Name KAI-9803 Phase 1/2 [23]
Synonyms
DELCASERTIB; UNII-5G7N7E908H; 5G7N7E908H; BMS-875944; Delcasertib [USAN:INN]; 949100-39-4; HY-106262; CS-0025460; L-Arginine, L-cysteinyl-L-tyrosylglycyl-L-arginyl-L-lysyl-L-lysyl-L-arginyl-L-arginyl-L- glutaminyl-L-arginyl-L-arginyl-, (1->1')-disulfide with L-cysteinyl-L-seryl-L-phenylalanyl-L- asparaginyl-L-seryl-L-tyrosyl-L-alpha-glutamyl-L-leucylglycyl-L-seryl-L-leucine; L-Cysteinyl-L-tyrosylglycyl-L-arginyl-L-lysyl-L-lysyl-L-arginyl-L-arginyl-L-glutaminyl-L- arginyl-L-arginyl-L-arginine (1->1')-d
    Click to Show/Hide
External Link
 Compound Name MDCO-216 Phase 1 [24]
External Link
 Compound Name PF-06282999 Phase 1 [25]
External Link
 Compound Name REC-01 Phase 1 [10]
External Link
 Compound Name Mesenchymal stem cell therapy, ischemic-tolerant stem cells Phase 1 [10]
External Link
 Compound Name Darexaban maleate Discontinued in Phase 3 [26]
Synonyms
UNII-03RTP2436R; 365462-24-4; 03RTP2436R; YM150; Darexaban maleate (JAN); SCHEMBL5406349; CHEMBL1922345; D09817; N-[2-[[4-(Hexahydro-4-methyl-1H-1,4-diazepin-1-yl)benzoyl]amino]-3-hydroxyphenyl]-4-methoxybenzamide (2Z)-2-Butenedioate
    Click to Show/Hide
External Link
 Compound Name Streptokinase Phase 4 [27]
External Link
 Compound Name RG1512 Discontinued in Phase 2 [28]
Synonyms
P-selectin huMAb
    Click to Show/Hide
External Link
 Compound Name LA-8045 Investigative [29]
Synonyms
LA-816
    Click to Show/Hide
External Link
References
Ref 1 Extracellular vesicle-packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction. Clin Transl Med. 2022 Apr;12(4):e779. doi: 10.1002/ctm2.779.
Ref 2 m6A methyltransferase METTL3 contributes to sympathetic hyperactivity post-MI via promoting TRAF6-dependent mitochondrial ROS production. Free Radic Biol Med. 2023 Nov 20;209(Pt 2):342-354. doi: 10.1016/j.freeradbiomed.2023.10.392. Epub 2023 Oct 26.
Ref 3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
Ref 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 5 Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy. Pharmacotherapy. 1990;10(2):115-26.
Ref 6 Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39(2-3):481-99.
Ref 7 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: 6586).
Ref 8 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: 7562).
Ref 9 ClinicalTrials.gov (NCT00914420) Optical Coherence Tomography (OCT) Evaluation of Re-endothelization: A Comparison of the Intrepide Stent Versus Taxus . U.S. National Institutes of Health.
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 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: 7835).
Ref 12 ClinicalTrials.gov (NCT01572909) Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events. U.S. National Institutes of Health.
Ref 13 ClinicalTrials.gov (NCT01848106) A Study To Determine the Efficacy and Safety of REG1 Compared to Bivalirudin in Patients Undergoing PCI. U.S. National Institutes of Health.
Ref 14 ClinicalTrials.gov (NCT02108262) A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.. U.S. National Institutes of Health.
Ref 15 ClinicalTrials.gov (NCT01554800) Effect of ACP-501 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Subjects With Coronary Artery Disease. U.S. National Institutes of Health.
Ref 16 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: 4048).
Ref 17 Clinical pipeline report, company report or official report of Avarx.
Ref 18 ClinicalTrials.gov (NCT01245634) A Study of RO4905417 in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery. U.S. National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT00409578) Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome. U.S. National Institutes of Health.
Ref 20 Clinical pipeline report, company report or official report of Momenta Pharmaceuticals.
Ref 21 Clinical pipeline report, company report or official report of Stemedica cell technologies.
Ref 22 ClinicalTrials.gov (NCT01412034) Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects. U.S. National Institutes of Health.
Ref 23 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: 7840).
Ref 24 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012886)
Ref 25 ClinicalTrials.gov (NCT01626976) A Study To Assess The Safety, Tolerability And Pharmacokinetics Of PF-06282999 Administered Orally In Healthy Adult Subjects. U.S. National Institutes of Health.
Ref 26 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020726)
Ref 27 ClinicalTrials.gov (NCT00302419) Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction. U.S. National Institutes of Health.
Ref 28 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025293)
Ref 29 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.