m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00436
 [1], [2], [3]
RNA modification MIR214 MIR214 ADARB1 Methylation : modification sites Indirect Inhibition m6A modification TP53 TP53 IGF2BP3 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
m6A Target Cellular tumor antigen p53 (TP53/p53)
 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 Double-stranded RNA-specific editase 1 (ADARB1) WRITER View Details
Regulated Target MicroRNA 214 (MIR214) View Details
Crosstalk Relationship A-to-I  →  m6A Inhibition
Crosstalk Mechanism RNA modification indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary ADARB1 interacts with MicroRNA 214 (MIR214), increasing it's A-to-I level and inhibiting its physical interaction with Cellular tumor antigen p53 (TP53/p53), which was regulated by IGF2BP3-mediated m6A modification.
In-vitro Model
 A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cellular tumor antigen p53 (TP53/p53) 27 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Contusugene ladenovec Phase 3 [4]
Synonyms
Advexin; Ad5CMV-p53; INGN-004; INGN-201; Ad-p53, Introgen; Gene therapy (p53/adenovirus), University of Texas; Gene therapy (p53/adenoviral), Introgen/Aventis; Gene therapy (p53/adenoviral), Introgen/RPR
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MOA Modulator
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TTD: D04FYL
 Compound Name QPI-1002 Phase 3 [5]
MOA Modulator
External Link
TTD: D0D5ZU
 Compound Name Thymoquinone Phase 2/3 [6]
Synonyms
490-91-5; Thymoquinon; p-Cymene-2,5-dione; 2-Isopropyl-5-methyl-1,4-benzoquinone; 2,5-CYCLOHEXADIENE-1,4-DIONE, 2-METHYL-5-(1-METHYLETHYL)-; 2-Isopropyl-5-methyl-p-benzoquinone; 2-Isopropyl-5-methylbenzoquinone; Polythymoquinone; 5-Isopropyl-2-methyl-1,4-benzoquinone; 2-Isopropyl-5-methylbenzo-1,4-quinone; p-Mentha-3,6-diene-2,5-dione; NSC 2228; 2-Isopropyl-5-methylcyclohexa-2,5-diene-1,4-dione; 2-Methyl-5-isopropyl-p-benzoquinone; 2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; NSC2228; 2-methyl-5-(propan-2-yl)cyclohexa-2,5-diene-1,4-dione; UNII-O60IE26NUF; 2-Methyl-5-isopropyl-1,4-benzoquinone; O60IE26NUF; 2,5-Cyclohexadiene-1,4-dione, 5-isopropyl-2-methyl-; NSC-2228; 5-Isopropyl-2-methyl-p-benzoquinone; MFCD00001602; 2-Methyl-5-(1-methylethyl)-2,5-cyclohexadiene-1,4-dione; p-Mentha-3,6-diene-2,5-dione (8CI); 5-Isopropyl-2-methyl-2,5-Cyclohexadiene-1,4-dione; CCRIS 7152; EINECS 207-721-1; 2-methyl-5-(methylethyl)cyclohexa-2,5-diene-1,4-dione; BRN 1939047; thymolquinone; Thymoil; AI3-17758; 4hco; p-Mentha-3,5-dione; Spectrum_001237; SpecPlus_000457; Thymoquinone, >=98%; Spectrum2_000700; Spectrum3_001345; Spectrum4_001895; Spectrum5_000550; BSPBio_003129; KBioGR_002455; KBioSS_001717; DivK1c_006553; SCHEMBL542535; SPBio_000859; CHEMBL1672002; DTXSID9060079; KBio1_001497; KBio2_001717; KBio2_004285; KBio2_006853; KBio3_002349; Thymoquinone, analytical standard; CHEBI:113532; 2-Methyl-5-iso-propylbenzoquinone; BDBM166686; ZINC164367; BCP16946; HY-D0803; WLN: L6V DVJ B1 EY1&1; 2,4-dione, 5-isopropyl-2-methyl-; ANW-41600; CCG-40027; s4761; SBB008296; AKOS003368628; MCULE-9899033250; NCGC00178250-01; NCGC00178250-05; 73940-92-8; AK101679; AS-11327; 2-Isopropyl-5-methylbenzo-1,4-quinone #; 2,4-dione, 2-methyl-5-(1-methylethyl)-; CS-0012226; FT-0612708; ST45023960; K-9199; SR-05000002192; Q7799650; SR-05000002192-2; W-202869; BRD-K97566842-001-03-5; 2-methyl-5-(propan-2-yl)cyclohexa-2,5-diene-1,4-dione (F8); 2-Methyl-5-(1-methylethyl)-2,5-cyclohexadiene-1,4-dione, 9CI
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MOA Inhibitor
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CID: 10281
TTD: DY4OZ6
 Compound Name SGT-53 Phase 2 [7]
Synonyms
P53 gene stimulator (solid tumor), Synergene Therapeutics
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MOA Stimulator
External Link
TTD: D02EOH
 Compound Name APR-246 Phase 2 [8]
Synonyms
Eprenetapopt
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MOA Stimulator
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CID: 52918385
TTD: D03XTY
DrugBank: DB11684
 Compound Name Ad-p53 Phase 2 [9]
Synonyms
P53 gene therapy, Transgene/Schering-Plough; Ad-p53, Transgene/Schering-Plough
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MOA Modulator
External Link
TTD: D0CO9B
 Compound Name Kevetrin Phase 2 [10]
MOA Stimulator
External Link
CID: 437740
TTD: D0K7DV
DrugBank: DB13010
 Compound Name INGN-225 Phase 2 [11]
Synonyms
Cancer vaccine (p53), Introgen
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External Link
TTD: D0V2SP
 Compound Name ALT-801 Phase 2 [12]
Synonyms
ALT-801 (donor lymphocyte infusion, cancer); ALT-801 (donor lymphocyte infusion, cancer), Altor; STAR IL-2 conjugate (donor lymphocyte infusion, cancer), Altor; STAR-Ck (donor lymphocyte infusion, cancer), Altor; Soluble T-cell Antigen Receptor IL-2 conjugate (donor lymphocyte infusion, cancer), Altor
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MOA Immunomodulator (Immunostimulant)
External Link
TTD: D0V5JH
 Compound Name APG-115 Phase 2 [10]
Synonyms
15Qau0SI9J; UNII-15QAU0SI9J; 1818393-16-6; APG 115 [WHO-DD]; SCHEMBL17189805; Bicyclo(2.2.2)octane-1-carboxylic acid, 4-((((3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-1'',2''-dihydro-2''-oxodispiro(cyclohexane-1,2'-pyrrolidine-3',3''-(3H)indol)-5'-yl)carbonyl)amino)-
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MOA Inhibitor
External Link
CID: 91972012
TTD: D04SXL
 Compound Name ISA-P53-01 Phase 1/2 [13]
Synonyms
P53-SLP; P53 vaccine (colorectal/ovarian cancer), ISA Pharmaceuticals; P53 vaccine (Montanide ISA-51 adjuvanted, colorectal/ovarian cancer), ISA Pharmaceuticals
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External Link
TTD: D0KK4N
 Compound Name SAR-405838 Phase 1 [14]
Synonyms
AT-219; MI-147; MI-219; MI-319; MI-43; MI-5; MI-63; MI-772; MI-773; MI-519-64; P53-HDM2 protein interaction inhibitors (cancer); P53-HDM2 protein interaction inhibitors (cancer), Ascenta/Sanofi; P53-HDM2 protein interaction inhibitors (cancer), Ascenta/sanofi-aventis
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MOA Modulator
External Link
CID: 53476877
TTD: D03YSQ
DrugBank: DB12541
 Compound Name Dendritic cell vaccine Phase 1 [15]
Synonyms
Dendritic cell vaccine (injectable, head and neck cancer); Dendritic cell vaccine (injectable, head and neck cancer), National Cancer Institute; Mutant p53 peptide pulsed dendritic cell vaccine (injectable, head and neck cancer), National Cancer Institute
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External Link
TTD: D05CPS
 Compound Name ONYX-015 Phase 1 [16]
Synonyms
Dl1520; E1B-deleted adenovirus (cancer), ONYX
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MOA Modulator
External Link
TTD: D0G7YS
 Compound Name COTI-2 Phase 1 [10]
Synonyms
UNII-2BTA1O65BR; 2BTA1O65BR; 1039455-84-9; ZINC114475331; CS-8156; HY-19896; 1-Piperazinecarbothioic acid, 4-(2-pyridinyl)-, 2-(6,7-dihydro-8(5H)-quinolinylidene)hydrazide
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MOA Modulator
External Link
CID: 91810660
TTD: D0G8CU
 Compound Name CGM097 Phase 1 [5]
MOA Modulator
External Link
CID: 53240420
TTD: D0Q7AG
 Compound Name HDM201 Phase 1 [17]
MOA Inhibitor
External Link
CID: 71678098
TTD: D01KTG
 Compound Name INGN-234 Discontinued in Phase 2 [18]
Synonyms
P53 tumor suppressor (topical formulation), Introgen
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MOA Suppressor
External Link
TTD: D05AHK
 Compound Name Pifithrin-alpha Terminated [19]
Synonyms
P53 inhibitor, Univ of Illinois; PFT-alpha; PFT-beta; Pifithrin compounds, Quark; Pifithrin-beta
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MOA Inhibitor
External Link
CID: 9929138
TTD: D02NYK
 Compound Name TAR-1 Terminated [20]
Synonyms
P53 protein modulator (single-chain antibody fragment, cancer), Ramot/Champions
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External Link
TTD: D0LG1K
 Compound Name 1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine Investigative [21]
Synonyms
PhiKan 083; [(9-ethyl-9H-carbazol-3-yl)methyl](methyl)amine; EN300-43214; 880813-36-5; AC1NGDXR; PhiKan-083; BAS 13152361; PhiKan-083 Hydrochloride; CHEMBL1235116; SCHEMBL20181195; AC1Q3123; ZINC3888893; STK511393; IMED102848735; AKOS000284549; MCULE-1841863738; DB08363; NCGC00379107-01; NCGC00379107-02; ST072505; [(9-ethylcarbazol-3-yl)methyl]methylamine; HY-108637; CS-0029368; [(9-ethylcarbazol-3-yl)methyl](methyl)amine; 1-(9-ethylcarbazol-3-yl)-N-methylmethanamine
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MOA Inhibitor
External Link
CID: 4722579
TTD: D08PLU
DrugBank: DB08363
 Compound Name NUTLIN-3 Investigative [22]
Synonyms
548472-68-0; 890090-75-2; nutlin-3A; nutlin 3; (+/-)-Nutlin3; CHEMBL211045; Nutlin 3(Random Configuration); MDM2 Antagonist, Nutlin-3, Racemic; 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one; 4-({4,5-bis(4-chlorophenyl)-2-[4-methoxy-2-(propan-2-yloxy)phenyl]-4,5-dihydro-1H-imidazol-1-yl}carbonyl)piperazin-2-one; 4-[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one
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MOA Inhibitor
External Link
CID: 216345
TTD: D01QKK
 Compound Name NU-8231 Investigative [23]
Synonyms
SCHEMBL2454464; CHEMBL360944
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MOA Inhibitor
External Link
CID: 11648438
TTD: D0F1SN
 Compound Name OPI-1002 Phase 2 [24]
External Link
TTD: D02CKH
 Compound Name Cenersen Phase 2 [24]
External Link
CID: 56841947
TTD: D0K4VW
 Compound Name AHL Investigative [24]
Synonyms
AHLi-11; SiRNA therapeutics (hearing loss), Quark; P53 gene-silencing siRNA (hearing loss), Quark
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External Link
TTD: D0T8EL
 Compound Name PC14586 Phase 1/2 [24]
External Link
TTD: D53CGK
References
Ref 1 Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung tumorigenesis via attenuating p53 stability. Oncotarget. 2017 Sep 27;8(55):93672-93687. doi: 10.18632/oncotarget.21280. eCollection 2017 Nov 7.
Ref 2 ADAR2-mediated editing of miR-214 and miR-122 precursor and antisense RNA transcripts in liver cancers. PLoS One. 2013 Dec 27;8(12):e81922. doi: 10.1371/journal.pone.0081922. eCollection 2013.
Ref 3 Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-kappaB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sci. 2020 Nov 15;261:118301. doi: 10.1016/j.lfs.2020.118301. Epub 2020 Aug 20.
Ref 4 A review of contusugene ladenovec (Advexin) p53 therapy. Curr Opin Mol Ther. 2009 Feb;11(1):54-61.
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 Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197. doi: 10.1016/j.drudis.2020.04.023. Epub 2020 May 7.
Ref 7 Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther. 2013 Apr;20(4):222-8. doi: 10.1038/cgt.2013.9. Epub 2013 Mar 8.
Ref 8 APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 2013 Oct 24;4(10):e881. doi: 10.1038/cddis.2013.417.
Ref 9 Assessment of p53 gene transfer and biological activities in a clinical study of adenovirus-p53 gene therapy for recurrent ovarian cancer. Cancer Gene Ther. 2003 Mar;10(3):224-38. doi: 10.1038/sj.cgt.7700562.
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther. 2010 Jun;10(6):983-91. doi: 10.1517/14712598.2010.484801.
Ref 12 Phase I trial of ALT-801, an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Clin Cancer Res. 2011 Dec 15;17(24):7765-75. doi: 10.1158/1078-0432.CCR-11-1817. Epub 2011 Oct 12.
Ref 13 WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
Ref 14 SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. Cancer Res. 2014 Oct 15;74(20):5855-65. doi: 10.1158/0008-5472.CAN-14-0799. Epub 2014 Aug 21.
Ref 15 Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother. 2004 Jul;53(7):633-41. doi: 10.1007/s00262-003-0493-5. Epub 2004 Feb 25.
Ref 16 Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell. 2004 Dec;6(6):611-23. doi: 10.1016/j.ccr.2004.11.012.
Ref 17 National Cancer Institute Drug Dictionary (drug id 761551).
Ref 18 Prevent Oral Cancer With Mouthwash. Introgen Therapeutics.
Ref 19 An evaluation of the ability of pifithrin-alpha and -beta to inhibit p53 function in two wild-type p53 human tumor cell lines. Mol Cancer Ther. 2005 Sep;4(9):1369-77. doi: 10.1158/1535-7163.MCT-04-0341.
Ref 20 Regulation of host gene expression by HIV-1 TAR microRNAs. Retrovirology. 2013; 10: 86.
Ref 21 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 22 Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. J Med Chem. 2009 Nov 26;52(22):7044-53. doi: 10.1021/jm900681h.
Ref 23 Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem. 2006 Oct 19;49(21):6209-21. doi: 10.1021/jm0601194.
Ref 24 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.