m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00128
 [1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification XIAP XIAP 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 X-linked inhibitor of apoptosis (XIAP) 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 X-linked inhibitor of apoptosis (XIAP) transcript.
Responsed Drug ASTX660
 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
HEK293 Normal Homo sapiens CVCL_0045
WI-38 Normal Homo sapiens CVCL_0579
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
X-linked inhibitor of apoptosis (XIAP) 50 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name ASTX660 Phase 2 [4]
Synonyms
YCXOHEXZVKOGEV-DNRQZRRGSA-N; 1799328-86-1; SCHEMBL16830758; CS-8216; HY-109565; 1-(6-(4-fluorobenzyl)-5-(hydroxymethyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-((2R,5R)-5-methyl-2-(((R)-3-methylmorpholino)methyl)piperazin-1-yl)ethan-1-one
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MOA Inhibitor
External Link
CID: 118169620
TTD: D01NUR
 Compound Name AEG35156 Phase 1/2 [5]
External Link
TTD: D0C1JP
 Compound Name EMBELIN Terminated [6]
Synonyms
550-24-3; Embelic acid; Emberine; 2,5-dihydroxy-3-undecylcyclohexa-2,5-diene-1,4-dione; 2,5-Dihydroxy-3-undecyl-1,4-benzoquinone; 2,5-Dihydroxy-3-undecyl-p-benzoquinone; 2,5-Dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-dione; UNII-SHC6U8F5ER; CHEBI:4778; Embelin, Embelia ribes; C17H26O4; NSC91874; XIAP inhibitor, Embelin; EINECS 208-979-8; NSC 91874; SHC6U8F5ER; BRN 1885786; Apoptosis Activator III, Embelin; AK115155; p-Benzoquinone, 2,5-dihydroxy-3-undecyl-; SR-01000597536; Spectrum_001513; Tocris-2156; SpecPlus_000501
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MOA Inhibitor
External Link
CID: 3218
TTD: D05HSW
 Compound Name ARPFAQK-FAM Investigative [6]
Synonyms
CHEMBL441156
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MOA Inhibitor
External Link
CID: 44460581
TTD: D09BKS
 Compound Name AVPIAQKSEK-FAM Investigative [6]
Synonyms
CHEMBL404788
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MOA Inhibitor
External Link
CID: 44460469
TTD: D0E7NV
 Compound Name SM-337 Investigative [7]
Synonyms
CHEMBL504559; GTPL7732; SCHEMBL12851753; BDBM50273699; (5S,8S,10aR)-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-3-(2-phenylacetyl)-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide
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MOA Inhibitor
External Link
CID: 25172871
TTD: D03KZH
 Compound Name SM-131 Investigative [8]
Synonyms
CHEMBL514738
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MOA Inhibitor
External Link
CID: 44589292
TTD: D0BW7P
 Compound Name BV-6 Investigative [9]
Synonyms
BV6
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MOA Inhibitor
External Link
CID: 23657864
TTD: D0O4UQ
 Compound Name SM-122 Investigative [7]
Synonyms
CHEMBL481422; Smac peptide mimetic 20; GTPL8855; SCHEMBL12105346; BDBM26218; bicyclic Smac peptide mimetic, 20; (3S,6S,10aS)-N-benzhydryl-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide
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MOA Inhibitor
External Link
CID: 24754886
TTD: D0Q7TL
 Compound Name AZD5582 Investigative [10]
Synonyms
AZD 5582; AZD-5582
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MOA Antagonist
External Link
CID: 49847690
TTD: D0VK7M
 Compound Name AT-406 Phase 3 [11]
Synonyms
1071992-99-8; SM 406; (5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide; CHEMBL2158051; QCR-136; UNII-N65WC8PXDD; N65WC8PXDD; AT406 (SM-406, ARRY-334543); J-501625; (5S,8S,10aR)-N-(Diphenylmethyl)-5-[(N-methyl-L-alanyl)amino]-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide; AT-406/Debio-1143
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External Link
CID: 25022340
TTD: D03MXK
 Compound Name Birinapant Phase 1/2 [11]
Synonyms
1260251-31-7; Birinapant (TL32711); TL-32711; UNII-6O4Z07B57R; TL 32711; 6O4Z07B57R; (2S)-N-[(2S)-1-[(2R,4S)-2-[[6-fluoro-2-[6-fluoro-3-[[(2R,4S)-4-hydroxy-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidin-2-yl]methyl]-1H-indol-2-yl]-1H-indol-3-yl]methyl]-4-hydroxypyrrolidin-1-yl]-1-oxobutan-2-yl]-2-(methylamino)propanamide
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External Link
CID: 49836020
TTD: D0E8NP
DrugBank: DB11782
 Compound Name Phenoxodiol Phase 1/2 [11]
Synonyms
Dehydroequol; Idronoxil; Haginin E; NV 06; NV-06; Idronoxil (USAN/INN); 2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl); 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol; 3-(4-Hydroxyphenyl)-2H-chromen-7-ol; 7-hydroxy-3-hydroxyphenyl-1H-benzopyran
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External Link
CID: 219100
TTD: D03YOS
DrugBank: DB04915
 Compound Name HGS-1029 Phase 1 [11]
Synonyms
AEG-40056; AEG-40057; AEG-40706; AEG-40730; AEG-40826; XIAP antagonists (anticancer), Aegera; Inhibitor of apoptosis (IAP) protein antagonists (cancer), Aegera/HGS; XIAP antagonists (small molecule, cancer), Aegera/HGS; Inhibitory apoptosis protein (IAP) antagonists (apoptosis stimulators, cancer), Aegera/HGS
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External Link
TTD: D02AMG
 Compound Name GDC-0152 Phase 1 [11]
Synonyms
GDC 0152; GDC0152
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External Link
CID: 46940575
TTD: D07CLV
DrugBank: DB12380
 Compound Name APG-1387 Phase 1 [11]
Synonyms
AKLBERUGKZNEJY-RTEPGWBGSA-N; SCHEMBL15490706
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External Link
CID: 73336238
TTD: D0NP8P
 Compound Name PMID25980951-Compound-40 Patented [11]
External Link
CID: 76282560
TTD: D00VXV
 Compound Name PMID25980951-Compound-29 Patented [11]
External Link
CID: 90155550
TTD: D01JEH
 Compound Name PMID25980951-Compound-15 Patented [11]
External Link
TTD: D03JHD
 Compound Name PMID25980951-Compound-31 Patented [11]
External Link
TTD: D03TQU
 Compound Name PMID25980951-Compound-30 Patented [11]
External Link
CID: 73603510
TTD: D08UPQ
 Compound Name PMID25980951-Compound-14 Patented [11]
External Link
TTD: D0EZ9G
 Compound Name PMID25980951-Compound-39 Patented [11]
External Link
CID: 76283048
TTD: D0G9CR
 Compound Name PMID25980951-Compound-33 Patented [11]
External Link
TTD: D0K2PK
 Compound Name PMID25980951-Compound-28 Patented [11]
External Link
TTD: D0NB0V
 Compound Name PMID25980951-Compound-10 Patented [11]
External Link
CID: 46175910
TTD: D0P9PZ
 Compound Name PMID25980951-Compound-11 Patented [11]
External Link
TTD: D0PF7S
 Compound Name PMID25980951-Compound-32 Patented [11]
External Link
CID: 72710867
TTD: D0Q1XF
 Compound Name PMID25980951-Compound-26 Patented [11]
External Link
TTD: D0S0XT
 Compound Name PMID25980951-Compound-13 Patented [11]
External Link
CID: 73296970
TTD: D0U5TX
 Compound Name PMID25980951-Compound-12 Patented [11]
External Link
TTD: D0UT1G
 Compound Name PMID25980951-Compound-45 Patented [11]
External Link
CID: 56924622
TTD: D0UU7G
 Compound Name PMID25980951-Compound-3 Patented [11]
External Link
CID: 90126716
TTD: D02UOD
 Compound Name PMID25980951-Compound-4 Patented [11]
External Link
TTD: D02ZHC
 Compound Name PMID25980951-Compound-21 Patented [11]
External Link
CID: 49818910
TTD: D03DQW
 Compound Name PMID25980951-Compound-42 Patented [11]
External Link
TTD: D03PTG
 Compound Name PMID25980951-Compound-22 Patented [11]
External Link
CID: 53239649
TTD: D03VPP
 Compound Name PMID25980951-Compound-37 Patented [11]
External Link
CID: 57389344
TTD: D07FRU
 Compound Name PMID25980951-Compound-36 Patented [11]
External Link
TTD: D0AC8H
 Compound Name PMID25980951-Compound-20 Patented [11]
External Link
CID: 67478013
TTD: D0CV9K
 Compound Name PMID25980951-Compound-38 Patented [11]
External Link
TTD: D0GF3P
 Compound Name PMID25980951-Compound-5 Patented [11]
External Link
TTD: D0ID3R
 Compound Name PMID25980951-Compound-41 Patented [11]
External Link
TTD: D0M3BY
 Compound Name PMID25980951-Compound-19 Patented [11]
External Link
TTD: D0MH4B
 Compound Name PMID25980951-Compound-7 Patented [11]
External Link
TTD: D0O8ZD
 Compound Name PMID25980951-Compound-6 Patented [11]
External Link
CID: 58491512
TTD: D09VAX
 Compound Name PMID25980951-Compound-27 Patented [11]
External Link
CID: 49847690
TTD: D0B6KC
 Compound Name PMID25980951-Compound-43 Patented [11]
External Link
CID: 52919959
TTD: D0HY5Q
 Compound Name PMID25980951-Compound-1 Patented [11]
External Link
CID: 68265428
TTD: D0R3YM
 Compound Name PMID25980951-Compound-44 Patented [11]
External Link
CID: 71661892
TTD: D0YN1X
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 ADAR1-mediated 3' UTR editing and expression control of antiapoptosis genes fine-tunes cellular apoptosis response. Cell Death Dis. 2017 May 25;8(5):e2833. doi: 10.1038/cddis.2017.12.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 Teaming up to tackle RNAi delivery challenge. Nat Rev Drug Discov. 2009 Jul;8(7):525-6. doi: 10.1038/nrd2940.
Ref 6 Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional... J Med Chem. 2004 May 6;47(10):2430-40.
Ref 7 Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins. J Med Chem. 2010 Sep 9;53(17):6361-7.
Ref 8 Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of ca... J Med Chem. 2008 Dec 11;51(23):7352-5.
Ref 9 IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell. 2007 Nov 16;131(4):669-81.
Ref 10 Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem. 2013 Dec 27;56(24):9897-919.
Ref 11 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.