m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00114
 [1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification IKBKB IKBKB 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 Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) 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 Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) transcript.
Responsed Drug Arsenic trioxide
 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
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) 18 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Arsenic trioxide Approved [4]
Synonyms
Arsenox; Arsentrioxide; Naonobin; Trisenox; Trixenox; Acide arsenieux [French]; Anhydride arsenieux [French]; Arseni trioxydum; Arsenic blanc [French]; Arsenic trioxide [JAN]; Arsenigen saure [German]; Arsenious Acid Anhydride; Arsenious trioxide; Arsenous oxide [ISO]; Oxyde Arsenieux; Arsenic trioxide [UN1561] [Poison]; Arsenic oxide (As2O3); Arsenic(III) trioxide; Oxyde Arsenieux [ISO-French]; Trisenox (TN); Arsenic trioxide (JP15/USAN); Arsenic(3+)
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MOA Inhibitor
External Link
CID: 14888
TTD: D07VIK
 Compound Name SAR-113945 Phase 2 [5]
Synonyms
S-0100229; S-0100658
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MOA Inhibitor
External Link
TTD: D0AE3U
 Compound Name IMD-1041 Phase 2 [6]
Synonyms
IMD-1041 (oral, COPD/interstitial cystis/type 2 diabetics/chronic inflammatory disease/metabolic syndrome/AD), IMMD
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MOA Inhibitor
External Link
TTD: D0V3CK
 Compound Name Parthenolide Phase 2 [7]
Synonyms
20554-84-1; (-)-Parthenolide; CHEBI:7939; Parthenolide, Tanacetum parthenium; 4,5-alpha-Epoxy-6-beta-hydroxygermacra-1(10),11(13)-dien-12-oic acid gamma-lactone; partenolide; C15H20O3; 29552-41-8; Prestwick2_000550; Prestwick3_000550; Epitope ID:115014; SCHEMBL8220; BSPBio_001308; BSPBio_000599; MLS002153872; CHEMBL465158; BPBio1_000659; SCHEMBL13367522; BCBcMAP01_000041; Parthenolide, > MolPort-008-268-168; MolPort-003-959-089; HMS1361B10; HMS3402B10; HMS1989B10; HMS1791B10; HMS1569N21; HMS2096N21
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MOA Inhibitor
External Link
CID: 7251185
TTD: D0M4KE
 Compound Name IMD-0354 Phase 1 [8]
Synonyms
IMD-2560; IMD-2560); I-kappaB kinase beta inhibitor (dermatological, atopic dermatitis/acne), Institute of Medicinal MolecularDesign; I-kappaB kinase beta inhibitor (oral, rheumatoid arthritis/osteoporosis), IMMD; IKK-beta inhibitor (dermatological, atopic dermatitis/acne), IMMD; IL-6 release inhibitor (oral, rheumatoid arthritis/osteoporosis), IMMD
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MOA Inhibitor
Activity IC50 = 218 nM
External Link
CID: 5081913
TTD: D0Z5DM
 Compound Name MLN0415 Discontinued in Phase 1 [9]
Synonyms
SCHEMBL3805703
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MOA Modulator
External Link
CID: 86630595
TTD: D06ZYC
 Compound Name 5-amino-2-phenyl-oxazole-4-carboxylic acid amide Investigative [10]
Synonyms
CHEMBL207987; 5-amino-2-phenyloxazole-4-carboxylic acid amide; 99185-68-9
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MOA Inhibitor
Activity IC50 = 11000 nM
External Link
CID: 11708263
TTD: D00XDG
 Compound Name 5-amino-2-p-tolyl-oxazole-4-carboxylic acid amide Investigative [10]
Synonyms
5-amino-2-(4-methylphenyl)-1,3-oxazole-4-carboxamide; CHEMBL382993; CTK6B8237; MolPort-000-894-518; SBB024037; BDBM50186628; STK351079; ZINC12394806; AKOS000313592; MCULE-2038651256
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MOA Inhibitor
Activity IC50 = 12700 nM
External Link
CID: 11543063
TTD: D01FPX
 Compound Name 3-amino-benzo[b]thiophene-2-carboxylic acid amide Investigative [10]
Synonyms
3-amino-1-benzothiophene-2-carboxamide; 37839-59-1; 3-Aminobenzo[b]thiophene-2-carboxamide; CHEMBL211002; Benzo[b]thiophene-2-carboxamide, 3-amino-; 3-aminobenzo[b]thiophene-2-carboxylic acid amide; AC1LGIJV; SCHEMBL6609258; CTK1B5350; DTXSID80356350; MolPort-002-798-643; ZINC339150; STL134701; BDBM50186634; AKOS001782516; CCG-127335; MCULE-9206749194; NE38914; EN300-88534
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MOA Inhibitor
Activity IC50 = 12600 nM
External Link
CID: 821974
TTD: D03PVS
 Compound Name 2-amino-5-phenylthiophene-3-carboxamide Investigative [10]
Synonyms
4815-35-4; 2-Amino-5-phenyl-thiophene-3-carboxylic acid amide; CHEMBL382565; 2-AMINO-5-PHENYL-3-THIOPHENECARBOXAMIDE; EN300-04586; AC1LDZKQ; ACMC-209kch; 3-thiophenecarboxamide, 2-amino-5-phenyl-; AC1Q5DNT; CBMicro_037044; Cambridge id 5914467; AC1Q4Z6N; Oprea1_326775; Oprea1_445444; SCHEMBL3510525; ZINC87504; CTK4J0691; DTXSID60351580; UHEGYTDIDBFUJD-UHFFFAOYSA-N; MolPort-000-223-057; HMS1757A19; ZX-AL001522; ANW-30639; STK346852; SBB015475; BDBM50186655; AKOS000274130; ACM4815354
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MOA Inhibitor
Activity IC50 = 1900 nM
External Link
CID: 703965
TTD: D06CBR
 Compound Name 3-amino-5-(4-chlorophenyl)thiophene-2-carboxamide Investigative [10]
Synonyms
175137-05-0; CHEMBL444884; 515142-45-7; 2-Thiophenecarboxamide,3-amino-5-(4-chlorophenyl)-; AC1MBTGN; 3-amino-5-(4-chlorophenyl)-2-thiophenecarboxamide; SCHEMBL4097325; CTK4D5319; DTXSID90373351; MQYJPACEBWKWEH-UHFFFAOYSA-N; MolPort-000-150-990; ZX-AT016871; ZINC2556119; SBB101177; BDBM50186632; 5704AD; AKOS022181810; AJ-39853; ACM175137050; RT-019539; FT-0704094; 3-Amino-5-(4-chloro-phenyl)-thiophene-2-carboxylic acid amide
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MOA Inhibitor
Activity IC50 = 6600 nM
External Link
CID: 2756390
TTD: D08VQM
 Compound Name 6-phenyl-thieno[3,2-d]pyrimidin-4-ylamine Investigative [10]
Synonyms
CHEMBL311108; CTK7E1320; ZINC13588156; BDBM50137196; AKOS015965750; 6-phenylthieno[3,2-d]pyrimidin-4-ylamine
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MOA Inhibitor
Activity IC50 = 970 nM
External Link
CID: 11499583
TTD: D09PLJ
 Compound Name 2-amino-quinoline-3-carboxylic acid amide Investigative [10]
Synonyms
2-aminoquinoline-3-carboxamide; 31407-28-0; 3-Quinolinecarboxamide, 2-amino-; 2-amino-3-quinolinecarboxamide; CHEMBL206956; GXZOXGRLLFZVGF-UHFFFAOYSA-N; ZERO/004541; AC1NP94V; SCHEMBL30837; CTK7D2638; MolPort-002-742-881; ZX-AN021879; ALBB-023365; STK735522; BDBM50186621; SBB012747; ZINC19890815; FCH854771; AKOS003368785; MCULE-6676169786; NCGC00340196-01; 2-Aminoquinoline-3-carboxylic acid amide; OR346178; KB-118564; 2-amino-3-quinolinecarboxamide, AldrichCPR; ST4128359; R9463
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MOA Inhibitor
Activity IC50 = 9600 nM
External Link
CID: 5200228
TTD: D0N1UB
 Compound Name SC-514 Investigative [11]
Synonyms
354812-17-2; Sc 514; SC514; 4-Amino-[2,3'-bithiophene]-5-carboxamide; 3-amino-5-(thiophen-3-yl)thiophene-2-carboxamide; CHEMBL193093; IKK-2 Inhibitor, SC-514; 5-(Thien-3-yl)-3-aminothiophene-2-carboxamide; C9H8N2OS2; GK 01140; Curator_000007; 4-Amino-[2,3-bithiophene]-5-carboxamide; BiomolKI_000076; BiomolKI2_000080; AC1MD9M6; 3-amino-5-thiophen-3-ylthiophene-2-carboxamide; Oprea1_591652; SCHEMBL4082097; KS-00000XLB; CHEBI:92464; ZINC81904; CTK8E9458; BDBM26098; SYN5231
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MOA Inhibitor
Activity IC50 = 1300 nM
External Link
CID: 2807869
TTD: D0T6VA
 Compound Name 4-amino-biphenyl-3-carboxylic acid amide Investigative [10]
Synonyms
CHEMBL207940; 5-phenylanthranilamide; 2-amino-5-phenylbenzamide; SCHEMBL3781950; Amino-substituted benzamide, 8c; BDBM27462; ZINC13686738
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MOA Inhibitor
Activity IC50 = 14500 nM
External Link
CID: 11600944
TTD: D0UP6G
 Compound Name Staurosporine Investigative [12]
Synonyms
Staurosporin; (+)-Staurosporine; Antibiotic 230; 62996-74-1; Antibiotic AM 2282; CCRIS 3272; AM-2282; UNII-H88EPA0A3N; Alkaloid AM-2282 from Streptomyces; H88EPA0A3N; CHEMBL388978; CHEBI:15738; CGP 39360; 8,12-Epoxy-1H,8H-2,7b,12a-triazadibenzo(a,g)cyclonona(cde)trinden-1-one, 2,3,9,10,11,12-hexahydro-9-methoxy-8-methyl-10-(methylamino)-, (8alpha,9beta,10beta,12alpha)-(+)-
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MOA Inhibitor
Activity IC50 = 1 nM
External Link
CID: 44259
TTD: D0E3TC
DrugBank: DB02010
 Compound Name 5-Bromo-6-methoxy-9H-beta-carboline Investigative [13]
Synonyms
5-bromo-6-methoxy-beta-carboline; CHEMBL310975; SCHEMBL6465779; BDBM50130233
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MOA Inhibitor
External Link
CID: 11414735
TTD: D01OBJ
 Compound Name PF-228 Investigative [14]
Synonyms
869288-64-2; PF-573228; PF 573228; PF573228; CHEMBL514554; 3,4-Dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone; 6-((4-((3-(Methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; 6-[4-(3-Methanesulfonyl-benzylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3,4-dihydro-1H-quinolin-2-one
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MOA Inhibitor
External Link
CID: 11612883
TTD: D02QAZ
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 deletion induces NFkappaB and interferon signaling dependent liver inflammation and fibrosis. RNA Biol. 2017 May 4;14(5):587-602. doi: 10.1080/15476286.2016.1203501. Epub 2016 Jun 30.
Ref 4 How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer. 2002 Sep;2(9):705-13.
Ref 5 The NF B pathway: a therapeutic target in glioblastoma. Oncotarget. 2011 August; 2(8): 646-653.
Ref 6 Inhibition of IKappaB phosphorylation prevents load-induced cardiac dysfunction in mice. Am J Physiol Heart Circ Physiol. 2012 Dec 15;303(12):H1435-45. doi: 10.1152/ajpheart.00290.2012. Epub 2012 Oct 5.
Ref 7 The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66. doi: 10.1016/s1074-5521(01)00049-7.
Ref 8 IKappaB kinase Beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. Clin Exp Allergy. 2011 Jan;41(1):104-15. doi: 10.1111/j.1365-2222.2010.03564.x.
Ref 9 Company report (Millennium)
Ref 10 Evolution of the thienopyridine class of inhibitors of IkappaB kinase-beta: part I: hit-to-lead strategies. J Med Chem. 2006 May 18;49(10):2898-908. doi: 10.1021/jm0510979.
Ref 11 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315. doi: 10.1042/BJ20070797.
Ref 12 UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst. 1996 Jul 17;88(14):956-65. doi: 10.1093/jnci/88.14.956.
Ref 13 Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22. doi: 10.1016/s0960-894x(03)00408-6.
Ref 14 Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52. doi: 10.1074/jbc.M606695200. Epub 2007 Mar 28.