m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00087
 [1], [2], [3], [4]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification eIF2AK2 eIF2AK2 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 Tyrosine-protein kinase EIF2AK2 (eIF2AK2/p68) 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 Tyrosine-protein kinase EIF2AK2 (eIF2AK2/p68) transcript.
Responsed Drug US9650366, 12
 Drug Info 
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
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Tyrosine-protein kinase EIF2AK2 (eIF2AK2/p68) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name US9650366, 12 Patented [5]
Synonyms
SCHEMBL17669987; BDBM308061
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 121268883
TTD: D05GPF
 Compound Name US9650366, 2 Patented [5]
Synonyms
SCHEMBL17669993; LHUVPYZTQHNXRU-UHFFFAOYSA-N; BDBM308050; 1-{2-[2-amino-5-(2H-tetrazol-5-yl)pyridin-3-yl]-1-benzothien-5-yl}-3-[4-chloro-3-(trifluoromethyl)phenyl]urea; 1-(2-(2-amino-5-(2H-tetrazol-5-yl)pyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 121268887
TTD: D0QZ4B
 Compound Name US9650366, 9 Patented [5]
Synonyms
SCHEMBL17670002; OGVARLFWIBVKET-UHFFFAOYSA-N; BDBM308058; N-[3-({5-[2-(3-hydroxypropyl)-2H-tetrazol-5-yl]pyridin-3-yl}ethynyl)phenyl]-3-methyl-2-furamide
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MOA Inhibitor
External Link
CID: 121268893
TTD: D0Z0BQ
 Compound Name ASN-11124542 Investigative [6]
Synonyms
AC1O5VPR; ASN 11124542
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MOA Inhibitor
External Link
CID: 6490494
TTD: D0C1DQ
 Compound Name indirubin derivative E804 Investigative [7]
Synonyms
indirubin E804; compound 2 [PMID: 21632247]
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MOA Inhibitor
External Link
CID: 6419764
TTD: D0N9DU
 Compound Name NU6140 Investigative [7]
Synonyms
Cdk2 Inhibitor IV, NU6140; 444723-13-1; NU 6140; CHEMBL1802728; 4-(6-Cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide; 4-{[6-(cyclohexylmethoxy)-7H-purin-2-yl]amino}-N,N-diethylbenzamide; Cdk2 inhibitor IV; SCHEMBL2169233; GTPL5949; CTK8E7940; DTXSID30436732; MolPort-023-276-742; MolPort-044-561-419; HMS3229E18; IN1369; ZINC22309248; BDBM50347924; AKOS024457537; CCG-206836; NCGC00370819-01; NU6140, > RT-011957; 4-(6-cyclohexylmethoxy-9hpurin-2-ylamino)-N,N-diethyl-benzamide
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MOA Inhibitor
Activity IC50 = 2000 nM
External Link
CID: 10202471
TTD: D04WFN
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 Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2alpha phosphorylation. J Mol Biol. 2009 Nov 6;393(4):777-87. doi: 10.1016/j.jmb.2009.08.070. Epub 2009 Sep 3.
Ref 4 Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR. J Biol Chem. 2019 Nov 29;294(48):18168-18180. doi: 10.1074/jbc.RA119.009113. Epub 2019 Oct 21.
Ref 5 Heterocycle-substituted pyridyl benzothiophenes as kinase inhibitors. US9650366.
Ref 6 Small molecule inhibitors of the RNA-dependent protein kinase. Biochem Biophys Res Commun. 2003 Aug 15;308(1):50-7.
Ref 7 Identification of new inhibitors of protein kinase R guided by statistical modeling. Bioorg Med Chem Lett. 2011 Jul 1;21(13):4108-14. doi: 10.1016/j.bmcl.2011.04.149. Epub 2011 May 13.