m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05823
 [1]
m6A modification hsa-miR-21-5p hsa-miR-21-5p METTL14 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-21-5p SMAD3  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target hsa-miR-21-5p
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-21-5p microRNA View Details
Regulated Target Mothers against decapentaplegic homolog 3 (SMAD3) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary METTL14 can regulate the Mothers against decapentaplegic homolog 3 (SMAD3) pathway by modulating hsa-miR-21-5p. METTL14 depletion induces trophoblast cell dysfunction by inhibiting miR-21-5p processing in an m6A-dependent manner.
Responsed Disease Abortion ICD-11: JA00.0
 Disease Info 
In-vitro Model
 HTR-8 Normal Homo sapiens CVCL_D728
In-vivo Model BALB/c mice (female) and C57BL/6 mice (male) (8-12 weeks-old, 20-22 g) were obtained from the Shanghai Laboratory Animal Center (Shanghai, China). Pregnancy day 0.5 (E0.5) was determined by measuring the vaginal plug. The m6A inhibitor, 3-deazaadenosine (40 μL at a concentration of 10 mg/kg dissolved in physiological saline; Sigma-Aldrich, St. Louis, MO, USA) was injected into the uterine cavity using a small catheter (Instech Laboratories, Plymouth Meeting, PA, USA) at E6.5, E5.5, and E4.5, respectively, whereas the control group was injected with an equal volume of saline solution. Mice were sacrificed at E10.5, embryo resorption was measured and photographed, and the placentas were collected. The resorbed embryos were small (<20 % of the average size), appeared dark with unclear boundaries between the fetus and the placenta, and showed necrosis.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Mothers against decapentaplegic homolog 3 (SMAD3) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name SIS-3 Preclinical [2]
Synonyms
SIS3 free base; Smad3 Inhibitor, SIS3; 1009104-85-1; Specific Inhibitor of Smad3; SIS3 (free base); (E)-1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one; 521985-36-4; Smad3 inhibitor SIS3; (E)-1-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-3-(1-methyl-2-phenylpyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one; SCHEMBL6479525; SCHEMBL6479530; CHEMBL4303604; CHEBI:87589; 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one; ZINC34299760; NCGC00387473-03; 6,7-Dimethyl-2-((2E)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl-prop-2-enoyl))-1,2,3,4-tetrahydroisoquinoline; HY-100444; CS-0019029; J3.550.832E; J-000258; Q27159754; (2E)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one; 2-Propen-1-one, 1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-
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MOA Inhibitor
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CID: 10138988
TTD: DF90DS
 Compound Name GNF-PF-2272 Investigative [3]
Synonyms
3-Methyltoxoflavin; MLS000528498; SMR000121073; 1,3,6-Trimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione; BAS 00444306; 1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione; 1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione; SR-01000322764; methyltoxoflavin; CPXHNWKHOFNPDO-UHFFFAOYSA-N; 3-methyl toxoflavin; AC1LA2XZ; 32502-62-8; cid_460747; SCHEMBL2180986; CHEMBL601757; BDBM34671; CHEBI:95315; KUC104460N; HMS2304H14; STK397047; KSC-1-228; MCULE-2510138695; NCGC00093522-02; NCGC00093522-01; HY-111117
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MOA Inhibitor
External Link
CID: 460747
TTD: D0P0CM
 Compound Name ELLAGIC ACID Investigative [3]
Synonyms
476-66-4; Benzoaric acid; Lagistase; Eleagic acid; Alizarine Yellow; Elagostasine; 2,3,7,8-Tetrahydroxychromeno[5,4,3-cde]chromene-5,10-dione; Ellagic acid dihydrate; Llagic acid; Acide ellagique; Acido elagico; Acidum ellagicum; C.I. 55005; Gallogen (VAN); Gallogen (astringent); C.I. 75270; Ellagate; Ellagic acid [INN:DCF]; UNII-19YRN3ZS9P; Acido elagico [INN-Spanish]; CCRIS 774; Gallogen, astringent; Acide ellagique [INN-French]; Acidum ellagicum [INN-Latin]; MLS000069632; C14H6O8; EINECS 207-508-3; NSC407286; NSC 40728
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MOA Inhibitor
External Link
CID: 5281855
TTD: D0A1CM
DrugBank: DB08846
JA00: Abortion 4 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Carboprost Tromethamine Approved [4]
Synonyms
Hemabate; Carboprost Trometanol; Carboprost trometamol; Carboprost tromethamine [USAN]; U 32921E; Hemabate (TN); Prostin / 15M; U-32921E; Prosta-5,13-dien-1-oic acid, 9,11,15-trihydroxy-15-methyl-, (5Z,9-alpha,11-alpha,13E,15S)-, compd. with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1); Prosta-5,13-dien-1-oic acid, 9,11,15-trihydroxy-15-methyl-, (5Z,9-alpha,11-alpha,13E,15S)-,compd. with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1); (15S)-15-Methylprostaglandin F(sub 2alpha) tromethamine; (15S)-15-Methylprostaglandin F2alpha tromethamine; (E)-7-[(1S,3S,5R)-3,5-dihydroxy-2-[(Z,3S)-3-hydroxy-3-methyloct-1-enyl]cyclopentyl]hept-5-enoic acid; (Z)-7-((1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(3S)-3-hydroxy-3-methyl-1-octenyl)cyclopentyl)-5-heptenoic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1); 15(S)15-Methyl pgf2-alpha tromethaminesalt; 15(S)15-Methyl prostaglandin F2-alpha tromethamine; 15-methylprostaglandin F2alpha-tromethamine
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External Link
CID: 5281074
TTD: D07PCI
 Compound Name Dinoprost Tromethamine Approved [5]
Synonyms
Dinolytic; Ensaprost; Lutalyse; Prostamate; Zinoprost; Panacelan F tromethamine salt; Pronalgon F; Prostalmon F; PGF2alpha THAM; PGF2alpha tromethamine; PROSTAGLANDIN F2ALPHA TRIS SALT; Prostaglandin F2a tromethamine; Prostaglandin F2alpha tham; Prostaglandin F2alpha tromethamine; Prostin F2 alpha; U 14585; Dinoprost tromethamine [USAN:JAN]; Dinoprost, trometamol salt; Enzaprost F compd. with trisamine; Lutalyse (Veterinary); PGF2-alpha tham; PGF2-alpha tris salt; PGF2-alpha tromethamine; PGF2-alpha tromethamine salt; PGF2alpha-Tris; Prostaglandin F(sub 2a) tromethamine; Prostaglandin F-2alpha tromethamine salt; Prostaglandin F2-alpha THAM; Prostaglandin F2-alpha THAM salt; Prostaglandin F2-alpha tromethamine; Prostin F2 alpha (TN); THAM PGF2-alpha; Tromethamine prostaglandin F2-alpha; U-14583E; Dinoprost tromethamine (JAN/USP); Protaglandin F2-alpha-tham salt; U-14,583E; Prosta-5,13-dien-1-oic acid, (5Z,9-alpha,11-alpha,13E,15S)-9,11,15-trihydroxy-, compd. with trimethylolaminomethane; Prosta-5,13-dien-1-oic acid, (5Z,9-alpha,11-alpha,13E,15S)-9,11,15-trihydroxy-,compd. with trimethylolaminomethane; Prosta-5,13-dien-1-oic acid, 9,11,15-trihydroxy-, (5Z,9alpha,11alpha,13E,15S)-, compd. with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1); (5Z,9alpha,11alpha,13E,15S)-9,11,15-Trihydroxyprosta-5,13-dienoic acid tris salt; (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1); (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid; 1,3-Propanediol, 2-amino-2-(hydroxymethyl)-, (5Z,9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oate (salt); 5-Heptenoic acid, 7-(3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl)-, tham; 7-(3,5-Dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl)-5-heptenoic acid, tromethamine salt
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CID: 5282415
TTD: D04RGA
DrugBank: DB01160
 Compound Name GLPG0974 Phase 2 [6]
Synonyms
compound 99 [PMID 25380412]
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External Link
CID: 57520598
TTD: D0TA4A
DrugBank: DB15406
 Compound Name Epostane Investigative [7]
Synonyms
Epostanum [Latin]; Epostano [Spanish]; WIN 32729; AC1L1HB6; Epostane [USAN:BAN:INN]; 4,5-epoxy-3,17-dihydroxy-4,17-dimethylandrost-2-ene-2-carbonitrile (4alpha,5alpha,17beta); Androst-2-ene-2-carbonitrile, 4,5-epoxy-3,17-dihydroxy-4,17-dimethyl-, (4alpha,5alpha,17beta)-; LS-19418; Androst-2-ene-2-carbonitrile, 3,17-dihydroxy-4,17-dimethyl-4,5-epoxy-, (4-alpha,5-alpha,17-beta)-
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CID: 6917713
TTD: D09SWM
References
Ref 1 METTL14 depletion induces trophoblast cell dysfunction by inhibiting miR-21-5p processing in an m6A-dependent manner. Int Immunopharmacol. 2024 Dec 5;142(Pt B):113200. doi: 10.1016/j.intimp.2024.113200. Epub 2024 Sep 27.
Ref 2 Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006 Feb;69(2):597-607. doi: 10.1124/mol.105.017483. Epub 2005 Nov 15.
Ref 3 In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
Ref 4 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017989.
Ref 5 Drug information of Dinoprost Tromethamine, 2008. eduDrugs.
Ref 6 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: 8417).
Ref 7 Termination of early pregnancy by the 3 beta-hydroxysteroid dehydrogenase inhibitor epostane. N Engl J Med. 1988 Sep 29;319(13):813-7.