m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02089
 [1]
DNA methylation DNMT1 FTO Indirect Enhancement m6A modification BDNF BDNF METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Neurotrophic factor BDNF precursor form (BDNF)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1) WRITER View Details
Regulated Target FTO alpha-ketoglutarate dependent dioxygenase (FTO) View Details
Crosstalk Relationship DNA methylation  →  m6A Enhancement
Crosstalk Mechanism DNA methylation indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO alpha-ketoglutarate dependent dioxygenase (FTO) promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO.
Responsed Disease Major depressive disorder ICD-11: 6A70.3
 Disease Info 
In-vitro Model
 SH-SY5Y Neuroblastoma Homo sapiens CVCL_0019
In-vivo Model Rats were housed at 23 ° C and 55% humidity and were given ad libitum food and water. During acclimatization (1 week), rats were placed randomly (3/cage); however, after initial behavioral testing, they were grouped according to their behavioral phenotypes. All experiments were performed under a light cycle (8:00 AM and 10:00 AM). The protocol to induce LH behavior was approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham. The animal study also adhered to the international guidelines for the use and care of laboratory animals.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DNA (cytosine-5)-methyltransferase 1 (DNMT1) 27 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name SGI110 Phase 3 [2]
MOA Modulator
External Link
CID: 137295284
TTD: D0Q5KZ
 Compound Name Guadecitabine Phase 3 [3]
Synonyms
UNII-2KT4YN1DP7; 929901-49-5; 2KT4YN1DP7; SGI-110 free acid; Guadecitabine [USAN:INN]; GuadecitabineSGI-110; Guadecitabine (USAN/INN); CHEMBL3544916; Guanosine, 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxy-; ZINC43203165; AKOS027321496; AKOS030238181; DB11918; CS-3089; HY-13542; D10877; 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxyguanosine
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 135564655
TTD: D0VZ4N
DrugBank: DB11918
 Compound Name CC-486 Phase 3 [4]
Synonyms
AG-14361; AG14361; 328543-09-5; UNII-48N0U0K50I; AG 14361; CHEMBL65892; 48N0U0K50I; Imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one, 2-[4-[(dimethylamino)methyl]phenyl]-5,6-dihydro-; AG-014361; 1-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one; Imidazo(4,5,1-jk)(1,4)benzodiazepin-7(4H)-one, 2-(4-((dimethylamino)methyl)phenyl)-5,6-dihydro-; 2-[4-[(Dimethylamino)methyl]phenyl]-5,6-dihydroimidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one; SMR000486393; MLS006011157; MLS001065917; Nucleoside analogue
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MOA Inhibitor
External Link
CID: 9840076
TTD: D09NTC
 Compound Name S-110 Phase 3 [5]
Synonyms
DNA demethylating agent (myelodysplastic syndrome), Supergen
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0A2BO
 Compound Name Palifosfamide Phase 2 [6]
Synonyms
ZIO-201
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 100427
TTD: D04FDN
DrugBank: DB05668
 Compound Name RX-3117 Phase 2 [7]
Synonyms
Antimetabolite (cancer), Rexahn; Antimetabolite (cancer), Rexahn/ Teva
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11242315
TTD: D0L7WS
 Compound Name Antroquinonol Phase 2 [8]
Synonyms
Hocena; Fungal extract (cancer), Golden Biotechnology
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 24875259
TTD: D0T3AW
DrugBank: DB12326
 Compound Name GSK4172239 Phase 1 [9]
MOA Inhibitor
External Link
TTD: D5QR2M
 Compound Name PMID27376512-Compound-miR-155-5p Patented [10]
MOA Inhibitor
Activity Ki = 27.88 nM
External Link
TTD: D01CGQ
 Compound Name PMID27376512-Compound-Table1Example11 Patented [10]
MOA Inhibitor
Activity IC50 = 39440 nM
External Link
CID: 75201485
TTD: D04JIH
 Compound Name PMID27376512-Compound-Table1Example16 Patented [10]
MOA Inhibitor
Activity IC50 = 22520 nM
External Link
CID: 75201537
TTD: D05DSL
 Compound Name PMID27376512-Compound-Table1Example5 Patented [10]
MOA Inhibitor
Activity IC50(DNMT1) = 3530 nM
External Link
CID: 73774653
TTD: D09FMS
 Compound Name PMID27376512-Compound-asCEBP-2HPE Patented [10]
MOA Inhibitor
Activity Ki = 135.2 nM
External Link
TTD: D0E7OA
 Compound Name PMID27376512-Compound-asCEBP-1 Patented [10]
MOA Inhibitor
Activity Ki = 2003 nM
External Link
TTD: D0G6ON
 Compound Name PMID27376512-Compound-Table1Example4 Patented [10]
MOA Inhibitor
Activity IC50 = 13810 nM
External Link
CID: 75201432
TTD: D0K4YF
 Compound Name PMID27376512-Compound-asCEBP-2 Patented [10]
MOA Inhibitor
Activity Ki = 434.1 nM
External Link
TTD: D0KE4E
 Compound Name PMID27376512-Compound-asCEBP-1HPE Patented [10]
MOA Inhibitor
Activity Ki = 917.5 nM
External Link
TTD: D0LK4R
 Compound Name PMID27376512-Compound-Table1Example8 Patented [10]
MOA Inhibitor
Activity IC50 = 6850 nM
External Link
CID: 75201482
TTD: D0RT6C
 Compound Name PMID27376512-Compound-MTC-433 Patented [10]
MOA Inhibitor
Activity IC50 = 4.22 nM
External Link
TTD: D0U5CK
 Compound Name PMID27376512-Compound-Table1Example30 Patented [10]
MOA Inhibitor
External Link
CID: 75201638
TTD: D0YK6K
 Compound Name PMID27376512-Compound-MTC-424 Patented [10]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [10]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [10]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [10]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
 Compound Name PMX-700 Investigative [11]
Synonyms
SJ-005019; SJ-005059; DC-010-116; Temozolomide analogs (cancer), Pharminox
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MOA Modulator
External Link
TTD: D03DTQ
 Compound Name XB-05 Investigative [11]
MOA Inhibitor
External Link
TTD: D0JV8Q
 Compound Name CP-4200 Investigative [11]
Synonyms
Lipidated azacitidine (cancer, Lipid Vector), Clavis Pharma; 5-azacytidine-5'-elaidate
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0OT1S
Neurotrophic factor BDNF precursor form (BDNF) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PYM-50028 Phase 2 [12]
Synonyms
Cogane; Smilagenin; P-58; P-63
    Click to Show/Hide
MOA Agonist
External Link
TTD: D0M2TG
References
Ref 1 M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C/EBPalpha-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats. Int J Neuropsychopharmacol. 2022 Dec 12;25(12):1037-1049. doi: 10.1093/ijnp/pyac068.
Ref 2 Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96.
Ref 5 S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010 May;9(5):1443-50.
Ref 6 Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84.
Ref 7 Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57.
Ref 8 Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential. J Agric Food Chem. 2014 Jun 18;62(24):5625-35.
Ref 9 Clinical pipeline report, company report or official report of GlaxoSmithKline
Ref 10 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
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. (Target id: 2605).
Ref 12 PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease. FASEB J. 2008 Jul;22(7):2488-97.