m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00131
 [1], [2], [3]
m6A modification ADAR1 ADAR1 METTL3 Methylation : m6A sites Direct Enhancement RNA modification PTK2 PTK2 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 Protein tyrosine kinase 2 (PTK2) 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 Protein tyrosine kinase 2 (PTK2) transcript.
Responsed Drug VS-6063
 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-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Protein tyrosine kinase 2 (PTK2) 11 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name VS-6063 Phase 2 [4]
Synonyms
Defactinib hydrochloride; 1073160-26-5; Defactinib (hydrochloride); UNII-L2S469LM49; Defactinib hydrochloride [USAN]; L2S469LM49; Defactinib hydrochloride (USAN); Benzamide, N-methyl-4-[[4-[[[3-[methyl(methylsulfonyl)amino]-2-pyrazinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-, hydrochloride; Defactinib HCl; Benzamide, N-methyl-4-((4-(((3-(methyl(methylsulfonyl)amino)-2-pyrazinyl)methyl)amino)-5-(trifluoromethyl)-2-pyrimidinyl)amino)-, hydrochloride (1:1); Benzamide, N-methyl-4-[[4-[[[3-[methyl(methylsu
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MOA Inhibitor
External Link
CID: 25117126
TTD: D0Y1UO
DrugBank: DB12282
 Compound Name BI-853520 Phase 1 [5]
MOA Modulator
External Link
TTD: D00KNI
 Compound Name PF-562271 Phase 1 [6]
Synonyms
PF-00562271
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MOA Inhibitor
Activity IC50 = 1 nM
External Link
CID: 11713159
TTD: D01SJT
 Compound Name VS-4718 Phase 1 [7]
Synonyms
PND-1186
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MOA Inhibitor
Activity IC50 = 1.5 nM
External Link
CID: 25073775
TTD: D0A6VD
DrugBank: DB15273
 Compound Name GSK-2256098 Phase 1 [8]
Synonyms
Focal adhesion kinase inhibitor (oral, cancer), GlaxoSmithKline
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MOA Inhibitor
External Link
CID: 46214930
TTD: D0B9MR
 Compound Name CEP-37440 Phase 1 [5]
Synonyms
Dual ALK/FAK inhibitor (cancer), Cephalon; Dual anaplastic lymphoma kinase/focal adhesion kinase inhibitor (cancer),Cephalon
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MOA Modulator
Activity IC50 = 80 nM
External Link
CID: 71721648
TTD: D0N6NM
DrugBank: DB13060
 Compound Name IN10018 Phase 1 [9]
MOA Inhibitor
External Link
TTD: D1EW3O
 Compound Name 1,2,4-triazolo[1,5a]pyridine derivative 1 Patented [10]
Synonyms
PMID27774824-Compound-Figure8compoundA
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MOA Inhibitor
Activity IC50 = 1100 nM
External Link
TTD: D07XYI
 Compound Name PMID23414845C30 Investigative [11]
Synonyms
4i4f; GTPL7864; BDBM50430287; 1BR
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MOA Inhibitor
Activity IC50 = 2200 nM
External Link
CID: 70698427
TTD: D0AY0F
 Compound Name PF-228 Investigative [12]
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
Activity IC50 = 50 nM
External Link
CID: 11612883
TTD: D02QAZ
 Compound Name BMS-536924 Investigative [13]
MOA Inhibitor
Activity IC50 = 150 nM
External Link
CID: 135440466
TTD: D0M4SY
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 Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. doi: 10.1093/jnci/djt210. Epub 2013 Sep 23.
Ref 5 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 6 Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45. doi: 10.1158/1535-7163.MCT-11-0261. Epub 2011 Sep 8.
Ref 7 FAK Inhibition disrupts a Beta5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. Mol Cancer Ther. 2014 Aug;13(8):2050-61. doi: 10.1158/1535-7163.MCT-13-1063. Epub 2014 Jun 4.
Ref 8 A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. doi: 10.4161/15384101.2014.949550.
Ref 9 Clinical pipeline report, company report or official report of InxMed.
Ref 10 Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1. Expert Opin Ther Pat. 2017 Feb;27(2):127-143. doi: 10.1080/13543776.2017.1252753. Epub 2016 Nov 7.
Ref 11 Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1779-85.
Ref 12 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.
Ref 13 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005 Sep 8;48(18):5639-43. doi: 10.1021/jm050392q.