m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02053
 [1]
DNA methylation DNMT1 FMR1 Direct Inhibition m6A modification GPX4 GPX4 FMR1 : m6A sites
m6A Modification:
m6A Regulator Synaptic functional regulator FMR1 (FMR1) READER
 Regulator Info 
m6A Target Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)
 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 Fragile X messenger ribonucleoprotein 1 (FMR1) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary USP7 was able to recruit DNMT1 to the FMR1 promoter region, which increased promoter methylation rates and suppressed FMR1 expression. TBK1 interacts with FMR1 to suppresses ferroptosis in renal tubular epithelial cells, manifested by decreased iron ion content and oxidative stress and increased cell viability and Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) expression level, thus alleviating I/R-induced renal injury
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Cell Process Cell proliferation
In-vitro Model
 HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
In-vivo Model All rats were housed under a 12 h light/dark cycle with constant temperature about 25 ° C and relative humidity approximating 55%. The rats had free access to food and water for 10 days prior to the experiment. After that, the renal ischemia-reperfusion injury rat model was established. SD rats were anesthetized with an intraperitoneal injection of pentobarbital sodium (25 mg/kg). Then an incision was made in the rat abdomen, and the right kidney was removed for nephrectomy. The left kidney was exposed after a midline incision, the renal artery was clamped for 45 min with a nontraumatic clamp, and renal blood flow was then restored.
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
GB60: Acute kidney failure 4 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name BQ788 Phase 3 [12]
Synonyms
(2R)-2-[[(2R)-2-amino-3-(1-methoxycarbonylindol-3-yl)propanoyl]-[(2S)-2-[[(2R,6S)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]hexanoic acid; BQ 788; AC1MIWQ3; GTPL1010; SCHEMBL18429752
    Click to Show/Hide
External Link
CID: 16759603
TTD: D08IXA
 Compound Name EA-230 Phase 2 [13]
Synonyms
503844-09-5; (2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-methylbutanoic acid; L-Valine, L-alanyl-L-glutaminylglycyl-; DTXSID80436085
    Click to Show/Hide
External Link
CID: 10133920
TTD: DL51QK
 Compound Name MB-102 Phase 2 [14]
Synonyms
Relmapirazin; UNII-Q3UQB8PQ6H; Q3UQB8PQ6H; Relmapirazin [INN]; CHEMBL1949708; SCHEMBL16738795; N,N'-((3,6-Diamino-2,5-pyrazinediyl)dicarbonyl)bis(D-serine); D-Serine, N,N'-((3,6-diamino-2,5-pyrazinediyl)dicarbonyl)bis-; 1313706-17-0
    Click to Show/Hide
External Link
CID: 53389120
TTD: D0C3JB
 Compound Name OPI-1002 Phase 2 [15]
External Link
TTD: D02CKH
References
Ref 1 USP7 accelerates FMR1-mediated ferroptosis by facilitating TBK1 ubiquitination and DNMT1 deubiquitination after renal ischemia-reperfusion injury. Inflamm Res. 2022 Dec;71(12):1519-1533. doi: 10.1007/s00011-022-01648-1. Epub 2022 Oct 20.
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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 13 Clinical pipeline report, company report or official report of Exponential Biotherapies.
Ref 14 ClinicalTrials.gov (NCT02772276) Pharmacokinetics of MB-102 and Use of the Non-invasive Optical Renal Function Monitor (ORFM) Device in Subjects With Normal and Impaired Renal Function and a Range of Skin Color Types. U.S. National Institutes of Health.
Ref 15 2011 Pipeline of Quark Pharm.