m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00129
 [1], [2], [3], [4]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification CCND1 CCND1 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 G1/S-specific cyclin-D1 (CCND1) 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 G1/S-specific cyclin-D1 (CCND1) transcript.
Responsed Drug ABT-263
 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
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
CFPAC-1 Cystic fibrosis Homo sapiens CVCL_1119
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
G1/S-specific cyclin-D1 (CCND1) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name ABT-263 Phase 3 [5]
Synonyms
Navitoclax; ABT 263; S1001_Selleck; ABT263, Navitoclax; 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-({(1R)-3-morpholin-4-yl-1-[(phenylsulfanyl)methyl]propyl}amino)-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide
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MOA Inhibitor
External Link
CID: 24978538
TTD: D06ETI
DrugBank: DB12340
 Compound Name Briciclib Phase 1 [6]
Synonyms
865783-99-9; ON-014185; UNII-WG93X96336; WG93X96336; ON 014185; Briciclib [USAN:INN]; Briciclib (USAN/INN); SCHEMBL1634579; SCHEMBL1634581; CHEMBL1206245; MolPort-046-033-539; LXENKEWVEVKKGV-BQYQJAHWSA-N; EX-A2492; BCP17292; ZINC28965775; AKOS027439966; DB12004; CS-5589; HY-16366; KB-79924; Briciclib(ON 013105 ON 014185); ON-013105; D10614; (2-methoxy-5-{[(E)-2-(2,4,6-trimethoxyphenyl)ethenesulfonyl]methyl}phenoxy)phosphonic acid; (e)-5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenyl dihydro
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MOA Inhibitor
External Link
CID: 11248490
TTD: D0T0KT
DrugBank: DB12004
 Compound Name 7-hydroxycoumarin Investigative [7]
Synonyms
Umbelliferone; 93-35-6; 7-Hydroxy-2H-chromen-2-one; Skimmetin; Hydrangin; 7-hydroxycoumarine; 7-Oxycoumarin; Umbelliferon; Skimmetine; Hydrangine; 2H-1-Benzopyran-2-one, 7-hydroxy-; 7-Hydroxy-2H-1-benzopyran-2-one; Coumarin, 7-hydroxy-; beta-Umbelliferone; 7-hydroxychromen-2-one; 7 HC; UNII-60Z60NTL4G; 7-hydroxy-coumarin; NSC 19790; CCRIS 3591; NSC19790; EINECS 202-240-3; 7H-1-Benzopyran-7-one, 2-hydroxy-; BRN 0127683; CHEMBL51628; AI3-38054; 7-hydroxy-1-benzopyran-2-one; 7-HC; 60Z60NTL4G; CHEBI:27510
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MOA Inhibitor
External Link
CID: 5281426
TTD: D02JEZ
 Compound Name 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [8]
Synonyms
CHEMBL380598; SCHEMBL3148490; HVQJGNALTWNDMX-UHFFFAOYSA-N; BDBM50375058; 2-(1H-Indole-3-yl)-3-phenylmaleimide
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MOA Inhibitor
External Link
CID: 15422868
TTD: D06AOY
 Compound Name 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Investigative [8]
Synonyms
1H-Pyrrole-2,5-dione, 3,4-bis(4-methoxyphenyl)-; 108774-82-9; ACMC-20mbs9; CHEMBL381099; CTK0G2626; DTXSID90449388
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MOA Inhibitor
External Link
CID: 10946795
TTD: D00NYT
 Compound Name 3,4-diphenyl-1H-pyrrole-2,5-dione Investigative [8]
Synonyms
2,3-diphenylmaleimide; 1H-Pyrrole-2,5-dione, 3,4-diphenyl-; 31295-36-0; AC1MBL6S; SCHEMBL114611; CHEMBL201949; CTK1B9880; 3,4-diphenylpyrrole-2,5-dione; DTXSID70372903; ZINC3847556
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MOA Inhibitor
External Link
CID: 2752461
TTD: D0C3WY
 Compound Name 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [8]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
CID: 11572699
TTD: D0EK0G
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [9]
MOA Inhibitor
External Link
CID: 9859248
TTD: D0A5RM
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 The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK. Sci Signal. 2017 Sep 19;10(497):eaah3941. doi: 10.1126/scisignal.aah3941.
Ref 4 CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing. Mol Cancer. 2021 Mar 9;20(1):51. doi: 10.1186/s12943-021-01333-7.
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 Clinical pipeline report, company report or official report of Onconova.
Ref 7 Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. Lung Cancer. 2001 Nov;34(2):185-94. doi: 10.1016/s0169-5002(01)00263-x.
Ref 8 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. doi: 10.1021/jm0580297.
Ref 9 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. doi: 10.1021/jm0605740.