m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02013
 [1]
m6A modification FENDRR FENDRR YTHDC1 : m6A sites Indirect Inhibition DNA methylation Epigenetic Regulator DRP1
m6A Modification:
m6A Regulator YTH domain-containing protein 1 (YTHDC1) READER
 Regulator Info 
m6A Target FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Regulated Target Dynamin-1-like protein (DRP1) View Details
Crosstalk Relationship m6A  →  DNA methylation Inhibition
Crosstalk Mechanism m6A modification indirectly regulates DNA methylation through downstream signaling pathways
Crosstalk Summary FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) overexpression inhibited hypoxia-induced HPAEC pyroptosis. Additionally, Dynamin-1-like protein (DRP1) is a downstream target gene of FENDRR, and FENDRR formed an RNA-DNA triplex with the promoter of DRP1, which led to an increase in DRP1 promoter methylation that decreased the transcriptional level of DRP1. Notably, we illustrated that the m6A reader YTHDC1 plays an important role in m6A-modified FENDRR degradation.
Responsed Disease Hypoxic pulmonary hypertension ICD-11: BB01.2
 Disease Info 
Cell Process Pyroptosis
In-vivo Model An aliquot of the vector at 1011 genome equivalents was prepared in 20-30 μL of HBSS and isoflurane anesthesia followed by nasal drops. Mice were randomly divided into five groups as follows: normoxic environment plus control vector group (NOR + NC, n = 20), hypoxic environment plus control vector group (HYP + NC, n = 10), hypoxic environment plus FENDRR TFO2 adenovirus group (HYP + FENDRR TFO2, n = 10), normoxic environment plus FENDRR TFO2 adenovirus group (NOR + FENDRR TFO2, n = 10).
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
BB01: Pulmonary hypertension 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name LU302146 Approved [2]
External Link
TTD: D0Y7OJ
 Compound Name Epoprostenol Approved [3]
Synonyms
Epoprostanol; Epoprostenolum; Flolan; PGX; Prostacyclin; Prostacycline; Prostacyclins; Vasocyclin; ProstaglandinI; Prostaglandin X; Prostaglandins X; PGI2; Prostacyclin I2; Prostaglandin I2; TRY 200; Epoprostenol (TN); Epoprostenol [USAN:INN]; Epoprostenolum [INN-Latin]; PG-I2; PGI(sub 2); Prostaglandin I(2); Try-200; U 53,217; U-53217; Epoprostenol (USAN/INN); KB-IV-24; (5E)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3R)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z)-5-[(4R,5R)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; (5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate; (5Z,13E,15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoic acid; (5Z,9alpha,11alpha,13E,15S)-11,15-dihydroxy-6,9-epoxyprosta-5,13-dien-1-oic acid; (5Z,9alpha,11alpha,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid; (Z)-(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-((E)-(3S)-3-hydroxy-1-octenyl)-2H-cyclopenta(b)furan-delta(sup 2,delta)-valeric acid; 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 5-[5-hydroxy-4-(3-hydroxyoct-1-enyl)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid; 6,9-alpha-Epoxy-11-alpha,15(S)-dihydroxyprosta-5(Z),13(E)-dien-1-oic acid
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CID: 5282411
TTD: D0V0IX
DrugBank: DB01240
 Compound Name Levosimendan Approved [4]
Synonyms
Levosimedan; Levosimendanum; Simdax; Levosimendan [INN]; Simdax (TN); Levosimendan (USAN/INN); Mesoxalonitrile(p-((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-pyridazinyl)phenyl)hydrazone; Mesoxalonitrile (-)-(p((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazone; ((4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile; (-)-OR-1259; (R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile; (R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile; ({4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}hydrazono)propanedintrile; 2-[[4-[(4R)-4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl]phenyl]hydrazinylidene]propanedinitrile
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CID: 3033825
TTD: D0C4HG
DrugBank: DB00922
 Compound Name Tolazoline Approved [5]
Synonyms
Artonil; Benzalolin; Benzazoline; Benzidazol; Benzolin; Benzylimidazoline; Divascol; Imidalin; Imidaline; Kasimid;Lambril; Olitensol; Peripherine; Phenylmethylimidazoline; Prefaxil; Pridazole; Priscol; Priscoline; Tolazolin; Tolazolina; Tolazolinum; Vasimid; Vasodil; Vasodilatan; Dilatol ASI; Tolazine [veterinary]; Tolazoline Monohydrochloride; Ciba 3259; Benzolin (VAN); Benzolin (vasodilator); Tolazine [veterinary] (TN); Tolazolina [INN-Spanish]; Tolazoline (INN); Tolazoline [INN:BAN]; Tolazolinum [INN-Latin]; Benzolin (vasodilator) (VAN); 1H-Imidazole, 4,5-dihydro-2-(phenylmethyl)-(9CI); 2-(phenylmethyl)-4,5-dihydro-1H-imidazole; 2-BENZYL-4,5-IMIDAZOLINE HCl; 2-Benzyl-2-imidazoline; 2-Benzyl-4,5-dihydro-1H-imidazole; 2-Benzyl-4,5-imidazoline; 2-Benzylimidazoline; 4,5-Dihydro-2-(phenylmethyl)-1H-imidazole
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CID: 5504
TTD: D03RZV
DrugBank: DB00797
 Compound Name Beraprost Phase 4 [6]
Synonyms
88430-50-6; 88430-50-6 (free acid); 1H-Cyclopenta(b)benzofuran-5-butanoic acid, 2,3,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyl-1-octen-6-ynyl)-; Beraprost (USAN); GTPL1967; SCHEMBL1554142; SCHEMBL1554145; BDBM85181; CAS_2352; NSC_2352; 4-[2-hydroxy-1-[(E)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoic acid; K578; D02720; L024061; Q5977854; (E)-4-(2-hydroxy-1-(3-hydroxy-4-methyloct-1-en-6-ynyl)-2,3,3a,8b-tetrahydro-1H-benzo[d]cyclopenta[b]furan-5-yl)butanoic acid; 4-(2-Hydroxy-1-(3-hydroxy-4-methyloct-1-en-6-yn-1-yl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl)butanoic acid; 4-{4-hydroxy-3-[(1E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]-7-oxatricyclo[6.4.0.0^{2,6}]dodeca-1(12),8,10-trien-9-yl}butanoic acid
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CID: 5282428
TTD: D4Q5AW
 Compound Name Bardoxolone methyl Phase 3 [4]
Synonyms
BARD; WPTTVJLTNAWYAO-OYWPANLISA-N; 218600-53-4
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CID: 400769
TTD: D0JU5X
DrugBank: DB05983
 Compound Name PF-1228305 Phase 3 [7]
Synonyms
Sitaxentan sodium; Sitaxsentan sodium
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CID: 11477084
TTD: D08JWJ
 Compound Name AZD3427 Phase 2 [8]
External Link
TTD: DHR39I
 Compound Name 99mTc-labelled adrenomedullin Phase 2 [9]
Synonyms
PulmoBind; DFH-12; Pulmonary disease imaging (intravenous), Pulmo BioTech; Pulmonary disease imaging (intravenous), PulmoScience; Technetium-99m labelled adrenomedullin (pulmonary disease), Pulmo BioTech; Technetium-99m labelled adrenomedullin (pulmonary disease), PulmoScience; 99mTc-labelled adrenomedullin (pulmonary disease), Pulmo BioTech
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TTD: D0WN1T
 Compound Name Ralinepag Phase 2 [10]
Synonyms
UNII-CQY12ZJN6E; CQY12ZJN6E; 1187856-49-0; Ralinepag [USAN:INN]; Ralinepag (USAN/INN); SCHEMBL1118504; SCHEMBL1118506; SCHEMBL12786473; CHEMBL3919269; CHEMBL3301604; AKOS027337124; DB12462; 2-((trans-4-((((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetic acid; Acetic acid, 2-((trans-4-(((((4-chlorophenyl)phenylamino)carbonyl)oxy)methyl)cyclohexyl)methoxy)-; HY-16751; CS-0012350; J3.614.088G; D10725
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CID: 44219292
TTD: D0M4TJ
DrugBank: DB12462
 Compound Name VentaProst Phase 2 [4]
External Link
TTD: D0HG9P
 Compound Name Autologous cell based gene therapy Phase 1 [11]
Synonyms
Autologous cell based gene therapy (pulmonary hypertension)
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TTD: D0H3GK
 Compound Name Dichloroacetate sodium Phase 1 [12]
Synonyms
Dichloroacetate sodium (pulmonary arterial hypertension), University of Alberta/Imperial College London
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CID: 517326
TTD: D01FQV
 Compound Name Prostacyclin analog Investigative [13]
Synonyms
Prostacyclin analog (deuterated, pulmonary hypertension)
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TTD: D06ENH
 Compound Name DasKloster 0247-01 Investigative [14]
External Link
TTD: D04UPJ
References
Ref 1 LncRNA FENDRR with m6A RNA methylation regulates hypoxia-induced pulmonary artery endothelial cell pyroptosis by mediating DRP1 DNA methylation. Mol Med. 2022 Oct 25;28(1):126. doi: 10.1186/s10020-022-00551-z.
Ref 2 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 3 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: 1915).
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 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: 7310).
Ref 6 ClinicalTrials.gov (NCT03431649) Efficacy of Beraprost in Lowering Pulmonary Arterial Pressure in Children. U.S. National Institutes of Health.
Ref 7 Pfizer. Product Development Pipeline. March 31 2009.
Ref 8 ClinicalTrials.gov (NCT05737940) A Phase IIb Randomised, Double-blind, Placebo-controlled, Multi-centre, Dose-ranging Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Due to Left Heart Disease (WHO Group 2). U.S.National Institutes of Health.
Ref 9 ClinicalTrials.gov (NCT02216279) Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension. U.S. National Institutes of Health.
Ref 10 ClinicalTrials.gov (NCT02279745) Long Term Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension. U.S. National Institutes of Health.
Ref 11 A Phase I study of the transplantation of genetically marked autologous bone marrow stromal cells. Hum Gene Ther. 1998 Mar 1;9(4):591-600.
Ref 12 ClinicalTrials.gov (NCT01083524) Dichloroacetate (DCA) for the Treatment of Pulmonary Arterial Hypertension. U.S. National Institutes of Health.
Ref 13 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. (Target id: 345).
Ref 14 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.