Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03240
[1]
m6A modification KDM6B KDM6B YTHDF2 : m6A sites Direct Inhibition Histone modification H3K27me3 KDM6B SLC7A11
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B) ERASER View Details
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3) View Details
Downstream Gene SLC7A11 View Details
Crosstalk Relationship m6A  →  Histone modification Inhibition
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary METTL3 induced Histone H3 lysine 27 trimethylation (H3K27me3) of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases Lysine-specific demethylase 6B (KDM6B) in a YTHDF2 manner.
In-vitro Model
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
In-vivo Model About 5 × 106 of MDA-MB-231 sh-NC or sh-METTL3 cells were injected subcutaneously into each 4-week-old immunodeficient BALB/c nude mice. Tumor formation was monitored, and tumor volume was calculated.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cystine/glutamate transporter (SLC7A11) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name SXC-2023 Phase 2 [2]
MOA Activator
External Link
Lysine-specific demethylase 6B (KDM6B) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name GSK-J1 Investigative [3]
Synonyms
GSK J1; 1373422-53-7; 3-{[2-(pyridin-2-yl)-6-(2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)pyrimidin-4-yl]amino}propanoic acid; 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; 3-[[2-Pyridin-2-Yl-6-(1,2,4,5-Tetrahydro-3-Benzazepin-3-Yl)pyrimidin-4-Yl]amino]propanoic Acid; GSKJ1; MLS006010249; GTPL7027; SCHEMBL10157115; CHEMBL3188597; BDBM60875; EX-A571; AOB3940; CHEBI:131152; MolPort-023-278-906; EX-A1744; BCP08262; ZINC95616592; s7581; 2442AH; AKOS024458240
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MOA Inhibitor
Activity IC50 = 16 nM
External Link
 Compound Name IOX1 Investigative [4]
Synonyms
5852-78-8; 8-Hydroxyquinoline-5-Carboxylic Acid; 8-Hydroxy-5-quinolinecarboxylic acid; 5-Carboxy-8-hydroxyquinoline; IOX 1; UNII-JM015YQC1C; IOX-1; 5-carboxy-8HQ; 5-Quinolinecarboxylic acid, 8-hydroxy-; JM015YQC1C; CHEMBL1230640; 4bio; 4jht; 8XQ; 4ie4; AC1LA0UV; MLS002729056; GTPL8230; SCHEMBL6068195; KS-00000PPH; CHEBI:93239; CTK1E0142; DTXSID20207236; AOB6499; JGRPKOGHYBAVMW-UHFFFAOYSA-N; MolPort-006-673-354; HMS3653E21; ZINC5933707; BCP16996; s7234; BDBM50396018; 2184AH; IOX1, > AKOS016371793
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MOA Inhibitor
Activity IC50 = 100 nM
External Link
References
Ref 1 N6-methyladenosine RNA modification regulates the transcription of SLC7A11 through KDM6B and GATA3 to modulate ferroptosis. J Biomed Sci. 2025 Jan 13;32(1):8. doi: 10.1186/s12929-024-01100-y.
Ref 2 Clinical pipeline report, company report or official report of Promentis Pharmaceuticals.
Ref 3 A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.
Ref 4 A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem. 2014 Mar;9(3):566-71. doi: 10.1002/cmdc.201300428. Epub 2014 Feb 6.