m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03312
 [1], [2]
Histone modification H3K4me3 MLL1 METTL3 Direct Enhancement m6A modification TNC TNC METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Tenascin (TNC)
 Targert Gene 
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 led to enhanced m6A levels of Tenascin (TNC) mRNA and promoted TNC mRNA stability.
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Cell Process Mitochondrial metabolic dysfunction
In-vitro Model
 HL-1 Normal Mus musculus CVCL_0303
AC16 [Human hybrid cardiomyocyte] Normal Homo sapiens CVCL_4U18
In-vivo Model METTL3 and TNC overexpression model was achieved by in situ injection of overexpression AAV9 into the heart of C57/BL mice, and the injected virus titers were 1.8 × 1012 PFU/mL. The stable overexpression of METTL3 and overexpression of TNC could be obtained after 3 weeks. The overexpression AAV9 was purchased from Hanheng Biotechnology Co., Ltd. (Shanghai, China). The vector was HBAAV2/9-CMV-m-METTL3-3xflag-Null and HBAAV2/9-CMV-m-TNC-3xflag-Null.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Tenascin (TNC) 4 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name F-16-IL-2 fusion protein Phase 2 [3]
Synonyms
Teleukin; F-16-IL-2; F-16-IL-2 fusion protein (cancer); F-16-IL-2 fusion protein (cancer), Philogen
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MOA Modulator
External Link
TTD: D0F1ZI
 Compound Name F-16-131I Phase 1/2 [4]
Synonyms
Tenarad; Radiolabeled scFv antibody F-16 (solid tumor/hematological malignancy), Philogen
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TTD: D0G1IG
 Compound Name 8H9 Phase 1 [5]
External Link
TTD: D06JAL
 Compound Name 131I-81C6 Terminated [6]
Synonyms
Neuradiab; MAb-81C6; Iodine-131-81C6; Astatine-211-MAb-81C6; Iodine-131-MAb-81C6; Iodine-131-ch-81C6; Iodine-131-ch-81C6-F(ab)2; 211At-MAb-81C6
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TTD: D07ZKK
BA41: Acute myocardial infarction 34 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Reteplase Approved [7]
Synonyms
Retevase; Rapilysin (TN); Retavase (TN); Retevase (TN); Reteplase (USAN/INN)
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TTD: D0T1UJ
 Compound Name M-enoxaparin Approved [8]
Synonyms
M-enoxaparin (angina)
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External Link
TTD: D0P2EX
 Compound Name Anistreplase Approved [9]
External Link
TTD: D0K4DI
 Compound Name Ridogrel Approved [10]
Synonyms
Ibidel; R-68070; Ridogrel (USAN/INN); 5-[(E)-[pyridin-3-yl-[3-(trifluoromethyl)phenyl]methylidene]amino]oxypentanoic acid
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CID: 5362391
TTD: D0E3BH
DrugBank: DB01207
 Compound Name Tisokinase Approved [8]
Synonyms
Plasvata (TN)
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TTD: D0E0ST
 Compound Name Tirofiban Approved [11]
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
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External Link
CID: 60947
TTD: D0BN9X
DrugBank: DB00775
 Compound Name Prasugrel Approved [12]
Synonyms
Effient (TN)
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External Link
CID: 6918456
TTD: D07IRF
DrugBank: DB06209
 Compound Name Trapidil Phase 4 [13]
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
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External Link
CID: 5531
TTD: D0U2CV
DrugBank: DB09283
 Compound Name Entresto Phase 3 [14]
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
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External Link
CID: 71449007
TTD: D0KQ8X
 Compound Name MultiStem Phase 2 [14]
Synonyms
MultiStem (TN)
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External Link
TTD: D0D7GS
 Compound Name Losmapimod Phase 3 [15]
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
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External Link
CID: 11552706
TTD: D0C8DD
DrugBank: DB12270
 Compound Name Bendavia Phase 2 [16]
Synonyms
Elamipretide
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External Link
CID: 11764719
TTD: D07TDV
DrugBank: DB11981
 Compound Name Dalcetrapib Phase 3 [14]
Synonyms
JTT 705; JTT-705; R-1658; RG-1658; RO-4607381; S-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methylpropanethioate
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External Link
CID: 6918540
TTD: D05SSC
DrugBank: DB12181
 Compound Name REG1 Phase 3 [17]
External Link
CID: 86278323
TTD: D05ALP
DrugBank: DB06293
 Compound Name RGN-352 Phase 2 [14]
Synonyms
Thymosin Beta 4 (injectable)
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External Link
TTD: DU04SO
 Compound Name CSL 112 Phase 2 [18]
External Link
TTD: DQY14Z
 Compound Name MEDI6012 Phase 1 [19]
Synonyms
RhLCAT; ACP-501
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External Link
TTD: D0T5YB
 Compound Name TF0023 Phase 2 [14]
External Link
TTD: D0PX0N
 Compound Name E5555 Phase 2 [20]
Synonyms
Atopaxar
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External Link
CID: 10459564
TTD: D0PU8T
DrugBank: DB12046
 Compound Name VT-111a Phase 2 [21]
External Link
TTD: D0O2XW
 Compound Name RO-4905417 Phase 2 [22]
External Link
TTD: D0M7VE
 Compound Name Aliskiren/valsartan Phase 2 [23]
Synonyms
Valturna (TN)
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External Link
CID: 23231644
TTD: D0LH4J
 Compound Name M118 Phase 2 [24]
Synonyms
Adomiparin
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External Link
CID: 21156139
TTD: D07XJJ
 Compound Name Ischemic tolerant allogeneic mesenchymal stem cell therapy Phase 2 [25]
External Link
TTD: D06ZCP
 Compound Name CER-001 Phase 2 [26]
External Link
TTD: D03AKH
 Compound Name KAI-9803 Phase 1/2 [27]
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
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CID: 56843747
TTD: D0O6HP
 Compound Name MDCO-216 Phase 1 [28]
External Link
TTD: D0L1ZK
 Compound Name PF-06282999 Phase 1 [29]
External Link
CID: 71571306
TTD: D09DXX
DrugBank: DB11683
 Compound Name REC-01 Phase 1 [14]
External Link
TTD: D03JWU
 Compound Name Mesenchymal stem cell therapy, ischemic-tolerant stem cells Phase 1 [14]
External Link
TTD: D01GQO
 Compound Name Darexaban maleate Discontinued in Phase 3 [30]
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
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External Link
CID: 49843900
TTD: D07OGZ
 Compound Name Streptokinase Phase 4 [31]
External Link
TTD: D04NCK
 Compound Name RG1512 Discontinued in Phase 2 [32]
Synonyms
P-selectin huMAb
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External Link
TTD: D03AUN
 Compound Name LA-8045 Investigative [33]
Synonyms
LA-816
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External Link
TTD: D0W3JA
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 TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner. Genes (Basel). 2023 Feb 26;14(3):591. doi: 10.3390/genes14030591.
Ref 3 National Cancer Institute Drug Dictionary (drug id 674718).
Ref 4 Tumor-Associated Fibroblasts and their Matrix. Springer. Margareta M. Mueller,Norbert E. Fusenig, 2011. Page(775).
Ref 5 In vitro and in vivo cytotoxic activities of recombinant immunotoxin 8H9(Fv)-PE38 against breast cancer, osteosarcoma, and neuroblastoma. Cancer Res. 2004 Feb 15;64(4):1419-24.
Ref 6 Human IgG2 constant region enhances in vivo stability of anti-tenascin antibody 81C6 compared with its murine parent. Clin Cancer Res. 1998 Oct;4(10):2495-502.
Ref 7 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
Ref 8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 9 Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy. Pharmacotherapy. 1990;10(2):115-26.
Ref 10 Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39(2-3):481-99.
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: 6586).
Ref 12 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 13 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 14 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 15 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 16 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 17 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 18 ClinicalTrials.gov (NCT02108262) A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.. U.S. National Institutes of Health.
Ref 19 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 20 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 21 Clinical pipeline report, company report or official report of Avarx.
Ref 22 ClinicalTrials.gov (NCT01245634) A Study of RO4905417 in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery. U.S. National Institutes of Health.
Ref 23 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 24 Clinical pipeline report, company report or official report of Momenta Pharmaceuticals.
Ref 25 Clinical pipeline report, company report or official report of Stemedica cell technologies.
Ref 26 ClinicalTrials.gov (NCT01412034) Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects. U.S. National Institutes of Health.
Ref 27 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 28 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 29 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 30 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 31 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 32 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 33 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.