m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00112
 [1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification AHR AHR ADAR Methylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Interferon-inducible protein 4 (ADAR1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> Adenosine-to-Inosine editing (A-to-I)
Epigenetic Regulator Interferon-inducible protein 4 (ADAR1) WRITER View Details
Regulated Target Aryl hydrocarbon receptor (AHR) View Details
Crosstalk Relationship m6A  →  A-to-I Enhancement
Crosstalk Mechanism m6A modification directly impacts RNA modification through modulating the expression level of RNA modification regulator
Crosstalk Summary METTL3 methylates Interferon-inducible protein 4 (ADAR1) mRNA, thereby enhancing its protein expression, which subsequently promotes ADAR mediated A-to-I RNA editing of the Aryl hydrocarbon receptor (AHR) transcript.
Pathway Response mRNA surveillance pathway hsa03015
RNA degradation hsa03018
Cell Process RNA stability
In-vitro Model
 MGG8 Glioblastoma Homo sapiens CVCL_D1H4
U-87MG ATCC Glioblastoma Homo sapiens CVCL_0022
U-118MG Astrocytoma Homo sapiens CVCL_0633
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Aryl hydrocarbon receptor (AHR) 10 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Tapinarof Approved [4]
Synonyms
GSK-2894512
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MOA Agonist
External Link
CID: 6439522
TTD: D03DMB
DrugBank: DB06083
 Compound Name Romiplostim Approved [5]
MOA Modulator
External Link
CID: 5329098
TTD: D01PZD
DrugBank: DB06436
 Compound Name RVT-505 Phase 2 [6]
MOA Modulator
External Link
TTD: D0AF5P
 Compound Name IK-175 Phase 1 [7]
MOA Antagonist
External Link
TTD: D5D6ZM
 Compound Name BAY 2416964 Phase 1 [8]
Synonyms
2242464-44-2; BAY2416964; SCHEMBL20471217; BCP33103; EX-A4271; MFCD32693912; NSC825713; s8995; NSC-825713; BAY-2416964; HY-135829; CS-0114330; BAY-2416964;BAY2416964; ClC1=CC=C(C=C1)C=1C=C(C(N(N=1)C=1C=NN(C=1)C)=O)C(=O)N[C@H](CO)C; (S)-6-(4-Chlorophenyl)-N-(1-hydroxypropan-2-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
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MOA Antagonist
External Link
CID: 135303769
TTD: DMVR61
 Compound Name AT-177 Clinical trial [9]
MOA Agonist
External Link
TTD: DNEH27
 Compound Name CB7993113 Preclinical [10]
MOA Antagonist
External Link
TTD: D49AGF
 Compound Name 2-(1H-indole-3,-carbonyl)-thiazole-4-carboxylic acid methyl ester Preclinical [11]
MOA Agonist
External Link
TTD: DQ3NC4
 Compound Name 6-Formylindolo[3,2-b]carbazole Investigative [12]
Synonyms
Indolo[3,2-b]carbazole-6-carbaldehyde; 1555757-10-2; indolo[3,2-b]carbazole-12-carbaldehyde; SCHEMBL528518; ANW-57186; MFCD23140892; ZINC39957465; AKOS015837457; AKOS025396684; FT-0678209
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MOA Agonist
External Link
CID: 22245026
TTD: DFBJ28
 Compound Name CH-223191 Investigative [13]
Synonyms
301326-22-7; CH 223191; CH223191; UNII-HYE7315Z4C; HYE7315Z4C; CHEMBL1743245; AhR Antagonist; 2-methyl-N-[2-methyl-4-[(2-methylphenyl)diazenyl]phenyl]pyrazole-3-carboxamide; 1-Methyl-N-[2-methyl-4-[2-(2-methylphenyl)diazenyl]phenyl-1H-pyrazole-5-carboxamide; 2-methyl-N-[2-methyl-4-(2-methylphenyl)azophenyl]-3-pyrazolecarboxamide; (E)-1-methyl-N-(2-methyl-4-(o-tolyldiazenyl)phenyl)-1H-pyrazole-5-carboxamide; 1-methyl-N-{2-methyl-4-[(E)-(2-methylphenyl)diazenyl]phenyl}-1H-pyrazole-5-carboxamide; 2-Methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide; CBDivE_007629; SCHEMBL363547; DTXSID5058698; AOB1977; EX-A771; SYN5007; CHEBI:125508; HMS3412G22; HMS3676G22; HMS3750E07; BCP12814; ZINC4762981; BDBM50525572; MFCD00377884; s7711; SBB081907; STK837883; 2-Methyl-2H-pyrazole-3-carboxylic acid-(2-methyl-4-o-tolyl-azophenyl)-amide; AKOS000629906; AKOS026750492; ZINC100550218; ZINC254429865; CCG-267843; CS-3905; MCULE-3225752823; 1H-Pyrazole-5-carboxamide, 1-methyl-N-(2-methyl-4-((2-methylphenyl)azo)phenyl)-; 1H-Pyrazole-5-carboxamide, 1-methyl-N-(2-methyl-4-(2-(2-methylphenyl)diazenyl)phenyl)-; AC-32878; AS-16374; HY-12684; QC-11824; FT-0696668; X3558; J-017795; BRD-K22314899-001-01-6; Q27216129; Q27280162; 1-methyl-N-{2-methyl-4-[2-(2-methylphenyl)diazen-1-yl]phenyl}-1H-pyrazole-5-carboxamide; N-{2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}(1-methylpyrazol-5-yl)carboxami de
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MOA Antagonist
External Link
CID: 3091786
TTD: DL36FJ
References
Ref 1 N?-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling. Genes (Basel). 2019 Feb 13;10(2):141. doi: 10.3390/genes10020141.
Ref 2 ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism. Genome Biol. 2021 Jan 28;22(1):51. doi: 10.1186/s13059-021-02271-9.
Ref 3 RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence. J Biol Chem. 2016 Jan 8;291(2):894-903. doi: 10.1074/jbc.M115.699363. Epub 2015 Nov 24.
Ref 4 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215272.
Ref 5 A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br J Cancer. 2005 Oct 17;93(8):876-83.
Ref 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 Clinical pipeline report, company report or official report of Ikena Oncology.
Ref 8 ClinicalTrials.gov (NCT04069026) A First-in-Humans Dose Finding Study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in Patients With Advanced Cancer. U.S. National Institutes of Health.
Ref 9 Clinical pipeline report, company report or official report of Azora Therapeutics
Ref 10 In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo. Mol Pharmacol. 2014 Nov;86(5):593-608.
Ref 11 1'H-Indole-3'-Carbonyl-Thiazole-4-Carboxylic Acid Methyl Ester Blocked Human Glioma Cell Invasion via Aryl Hydrocarbon Receptor's Regulation of Cytoskeletal Contraction. Biomed Res Int. 2020 Oct 3;2020:2616930.
Ref 12 6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression. Chem Biol Interact. 2018 May 25;288:83-90.
Ref 13 Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol Pharmacol. 2006 Jun;69(6):1871-8.