Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00567
[1], [2], [3]
m6A modification pri-miR-143 pri-miR-143 VIRMA Methylation : m6A sites Indirect Enhancement RNA modification STAT3 STAT3 ADAR Methylation : modification sites
m6A Modification:
m6A Regulator Protein virilizer homolog (VIRMA) WRITER
m6A Target pri-miR-143
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 Signal transducer and activator of transcription 3 (STAT3) View Details
Crosstalk Relationship m6A  →  A-to-I Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary VIRMA interacts with pri-miR-143, increasing its m6A level and promoting its physical interaction with Signal transducer and activator of transcription 3 (STAT3), which was regulated by ADAR1-mediated A-to-I modification.
In-vitro Model
LB
N.A. Homo sapiens CVCL_E751
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Signal transducer and activator of transcription 3 (STAT3) 74 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Acitretin Approved [4]
Synonyms
Acitretina; Acitretine; Acitretinum; Etretin; Isoacitretin; Isoetretin; Neotigason; Soriatane; TMMP; Acitretina [Spanish]; Acitretine [French]; Acitretinum [Latin]; Retinoid etretin; U0279; Ro 10-1670; Ro 13-7652; Soriatane (TN); Soriatane, Acitretin; Acitretin (USAN/INN); Acitretin [USAN:INN:BAN]; All-trans-Acitretin; Ro 10-1670/000; Ro-10-1670; Ro-13-7652; Ro-10-1670/000; All-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acid; (2E,4E,6E,8E)-3,7-dimethyl-9-[2,3,6-trimethyl-4-(methyloxy)phenyl]nona-2,4,6,8-tetraenoic acid; (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid; (all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; 13-cis-Acitretin; 9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; 9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Napabucasin Phase 3 [5]
Synonyms
83280-65-3; UNII-Z1HHM49K7O; 2-acetylnaphtho[2,3-b]furan-4,9-dione; Z1HHM49K7O; 2-Acetylnaphtho(2,3-b)furan-4,9-dione; 2-Acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione; Napabucasin [USAN:INN]; Napabucasin (BBI608); 2-Acetylfuranonaphthoquinone; CHEMBL64130; Napabucasin (JAN/USAN/INN); SCHEMBL1883845; Napabucasin - BBI 608/ FNQ; 2-Acetylfuro-1,4-naphthoquinone; DPHUWDIXHNQOSY-UHFFFAOYSA-N; MolPort-039-101-321; EX-A1314; ZINC13306865; s7977; AKOS027470201; DB12155; CS-1747; ACN-053294; HY-13919
    Click to Show/Hide
MOA Inhibitor
Activity EC50 = 1900 nM
External Link
 Compound Name Golotimod Phase 2 [6]
Synonyms
229305-39-9; SCV-07; gamma-D-Glu-L-trp; SCV07; gamma-D-Glutamyl-L-tryptophan; SCV 07; UNII-637C487Y09; 637C487Y09; (R)-2-Amino-5-(((S)-1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-5-oxopentanoic acid; Golotimod [USAN:INN]; (2R)-2-amino-5-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-5-oxopentanoic acid; (2R)-2-Amino-5-(((1S)-1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-5-oxopentanoic acid; Golotimod (USAN/INN); GAMMA-D-GLU-TRP-OH; H-D-Glu(L-Trp-OH)-OH; SCHEMBL727944; (gamma-glutamyl-L-tryptophan); CHEMBL2103812; Golotimod (oral); Golotimod (oral), SciClone/Verta; SCV-07 (oral, tuberculosis), SciClone/Verta
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Atiprimod Phase 1/2 [7]
Synonyms
Atiprimod [INN]; SKF 106615; SKF-106615; N,N-Diethyl-8,8-dipropyl-2-azaspiro(4.5)decane-2-propanamine; 3-(8,8-dipropyl-3-azaspiro[4.5]decan-3-yl)-N,N-diethylpropan-1-amine
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name OPB-31121 Phase 1/2 [8]
MOA Inhibitor
External Link
 Compound Name IMX-110 Phase 1/2 [5]
MOA Inhibitor
External Link
 Compound Name GLG-801 Phase 1/2 [5]
MOA Inhibitor
External Link
 Compound Name WP-1066 Phase 1/2 [5]
Synonyms
WP1066; 857064-38-1; (S,E)-3-(6-Bromopyridin-2-yl)-2-cyano-N-(1-phenylethyl)acrylamide; WP 1066; UNII-63V8AIE65T; 63V8AIE65T; AK-99218; C17H14BrN3O; (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]prop-2-enamide; MLS006010178; SCHEMBL1315826; QCR-16; SCHEMBL1315831; GTPL7972; CHEMBL1923234; EX-A760; AOB1497; DTXSID50235007; MolPort-044-723-708; MolPort-023-219-149; ZINC13983221; AKOS016007983; WP1066/WP-1066; CS-2736; DB12679; 2-Propenamide, 3-(6-bromo-2-pyridinyl)-2-cyano-N-((1S)-1-phenylethyl)-, (2E)-; HY-15312
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name NT219 Phase 1/2 [9]
Synonyms
UNII-K1WT1A1UP5; K1WT1A1UP5; 1198078-60-2; (E)-3-(2-Bromo-3,4-dihydroxyphenyl)-N-(3,4,5-trihydroxybenzyl)prop-2-enethioamide; CHEMBL3679680; SCHEMBL12659248; BDBM101913; NT-219; US8536227, 5; 2-Propenethioamide, 3-(2-bromo-3,4-dihydroxyphenyl)-N-((3,4,5-trihydroxyphenyl)methyl)-; 2-Propenethioamide, 3-(2-bromo-3,4-dihydroxyphenyl)-N-((3,4,5-trihydroxyphenyl)methyl)-, (2E)-
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name OPB-51602 Phase 1 [10]
MOA Inhibitor
External Link
 Compound Name TAK-114 Phase 1 [11]
MOA Modulator
External Link
 Compound Name WP1220 Phase 1 [12]
Synonyms
mol4239; MOL-4239; PTN9LJL6PY; UNII-PTN9LJL6PY; WP-1220; 2,4-Pentadienamide, 5-(6-bromo-2-pyridinyl)-2-cyano-N-((1S)-1-phenylethyl)-, (2E,4E)-; 1204306-34-2; SCHEMBL862248; SCHEMBL1316581; CHEMBL4594434; (2E,4E)-5-(6-Bromo-2-pyridinyl)-2-cyano-N-((1S)-1-phenylethyl)-2,4-pentadienamide; (2E,4E)-5-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]penta-2,4-dienamide
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name DSP-0337 Phase 1 [13]
MOA Inhibitor
External Link
 Compound Name OPB-111077 Phase 1 [14]
MOA Inhibitor
External Link
 Compound Name Quinoline carboxamide derivative 2 Patented [15]
Synonyms
PMID26394986-Compound-29
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Peptidomimetic analog 3 Patented [15]
Synonyms
PMID26394986-Compound-5
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-11 Patented [15]
MOA Inhibitor
External Link
 Compound Name Flavonoid derivative 5 Patented [15]
Synonyms
PMID26394986-Compound-49
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Salicylic acid derivative 6 Patented [15]
Synonyms
PMID26394986-Compound-18
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 10000 nM
External Link
 Compound Name Gold-complexed thiosaccharide derivative 2 Patented [15]
Synonyms
PMID26394986-Compound-67
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Peptidomimetic analog 1 Patented [15]
Synonyms
PMID26394986-Compound-3
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 125 nM
External Link
 Compound Name Quinoline carboxamide derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-28
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 74000 nM
External Link
 Compound Name Salicylic acid derivative 4 Patented [15]
Synonyms
PMID26394986-Compound-16
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-12 Patented [15]
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-21 Patented [15]
MOA Inhibitor
Activity IC50 = 15000 nM
External Link
 Compound Name Salicylic acid derivative 5 Patented [15]
Synonyms
PMID26394986-Compound-17
    Click to Show/Hide
MOA Inhibitor
Activity Kd = 300 nM
External Link
 Compound Name PMID26394986-Compound-20 Patented [15]
MOA Inhibitor
Activity IC50 = 45000 nM
External Link
 Compound Name PMID26394986-Compound-43 Patented [15]
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-50 Patented [15]
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-44 Patented [15]
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-51 Patented [15]
MOA Inhibitor
External Link
 Compound Name Salicylic acid derivative 3 Patented [15]
Synonyms
PMID26394986-Compound-14a
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 12800 nM
External Link
 Compound Name Quinoline carboxamide derivative 3 Patented [15]
Synonyms
PMID26394986-Compound-30
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Pyrazole derivative 62 Patented [15]
Synonyms
PMID26394986-Compound-23
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Pyrazole derivative 63 Patented [15]
Synonyms
PMID26394986-Compound-24
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Flavonoid derivative 3 Patented [15]
Synonyms
PMID26394986-Compound-47
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Peptide analog 7 Patented [15]
Synonyms
PMID26394986-Compound-1
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Salicylic acid derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-13a
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2800 nM
External Link
 Compound Name Gold-complexed thiosaccharide derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-66
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Gold-complexed thiosaccharide derivative 3 Patented [15]
Synonyms
PMID26394986-Compound-68
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-22 Patented [15]
MOA Inhibitor
External Link
 Compound Name Pyrazole derivative 65 Patented [15]
Synonyms
PMID26394986-Compound-26
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Pyrazole derivative 64 Patented [15]
Synonyms
PMID26394986-Compound-25
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-42 Patented [15]
MOA Inhibitor
External Link
 Compound Name Peptidomimetic analog 2 Patented [15]
Synonyms
PMID26394986-Compound-4
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 17 nM
External Link
 Compound Name Pyrazole derivative 66 Patented [15]
Synonyms
PMID26394986-Compound-27
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-52 Patented [15]
MOA Inhibitor
External Link
 Compound Name Salicylic acid derivative 2 Patented [15]
Synonyms
PMID26394986-Compound-14
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 19000 nM
External Link
 Compound Name Salicylic acid derivative 7 Patented [15]
Synonyms
PMID26394986-Compound-19
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 10000 nM
External Link
 Compound Name PMID26394986-Compound-53 Patented [15]
MOA Inhibitor
External Link
 Compound Name Flavonoid derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-45
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-54 Patented [15]
MOA Inhibitor
External Link
 Compound Name Peptidomimetic analog 4 Patented [15]
Synonyms
PMID26394986-Compound-6
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-13 Patented [15]
MOA Inhibitor
Activity IC50 = 35000 nM
External Link
 Compound Name Tri-substituted purine derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-9
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Flavonoid derivative 4 Patented [15]
Synonyms
PMID26394986-Compound-48
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Flavonoid derivative 2 Patented [15]
Synonyms
PMID26394986-Compound-46
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PMID26394986-Compound-Figure16 Patented [15]
MOA Inhibitor
Activity IC50 < 150 nM
External Link
 Compound Name PMID26394986-Compound-Figure17 Patented [15]
MOA Inhibitor
External Link
 Compound Name Oxazole derivative 1 Patented [15]
Synonyms
PMID26394986-Compound-8
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 79000 nM
External Link
 Compound Name Curcumin analog 2 Patented [15]
Synonyms
PMID26394986-Compound-33
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name Curcumin analog 1 Patented [15]
Synonyms
PMID26394986-Compound-32
    Click to Show/Hide
MOA Inhibitor
Activity Kd = 172 nM
External Link
 Compound Name Peptidomimetic analog 5 Patented [15]
Synonyms
PMID26394986-Compound-7
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 310000 nM
External Link
 Compound Name Platinum IV complexe 1 Patented [15]
Synonyms
PMID26394986-Compound-69
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1400 nM
External Link
 Compound Name PMID26394986-Compound-10 Patented [15]
MOA Inhibitor
Activity IC50 = 86000 nM
External Link
 Compound Name GNF-PF-1399 Investigative [16]
Synonyms
GNF-PF-2708; GNF-PF-4643
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name ISIS-STAT3 Phase 1/2 [17]
External Link
 Compound Name C188-9 Phase 1 [17]
Synonyms
QDCJDYWGYVPBDO-UHFFFAOYSA-N; UNII-KZ3DLD11RQ; KZ3DLD11RQ; AC1LQFBK; MLS006011646; SCHEMBL16394007; CHEMBL3392776; MolPort-000-644-242; N-(1B; ZINC1154831; AKOS001673470; MCULE-7568979350; NCGC00262829-02; SMR004703404; EU-0081697; AB00117290-01; C-188-9; N-[4-hydroxy-3-(2-hydroxynaphthalen-1-yl)naphthalen-1-yl]-4-methoxybenzenesulfonamide; N-[4-hydroxy-3-(2-hydroxy-1-naphthyl)-1-naphthyl]-4-methoxy-1-benzenesulfonamide; Benzenesulfonamide, N-(1',2-dihydroxy(1,2'-binaphthalen)-4'-yl)-4-methoxy-; 432001-19-9
    Click to Show/Hide
External Link
 Compound Name ISIS 113187 Investigative [17]
External Link
 Compound Name ISIS 113176 Investigative [17]
External Link
 Compound Name ISIS 113209 Investigative [17]
External Link
 Compound Name ISIS 113210 Investigative [17]
External Link
 Compound Name ISIS 17148 Investigative [17]
External Link
 Compound Name ISIS 17152 Investigative [17]
External Link
References
Ref 1 Alternative Splicing of STAT3 Is Affected by RNA Editing. DNA Cell Biol. 2017 May;36(5):367-376. doi: 10.1089/dna.2016.3575. Epub 2017 Mar 9.
Ref 2 KIAA1429 and ALKBH5 Oppositely Influence Aortic Dissection Progression via Regulating the Maturation of Pri-miR-143-3p in an m6A-Dependent Manner. Front Cell Dev Biol. 2021 Aug 19;9:668377. doi: 10.3389/fcell.2021.668377. eCollection 2021.
Ref 3 CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Ralpha1 and STAT3. Biochem Genet. 2021 Apr;59(2):531-546. doi: 10.1007/s10528-020-10003-0. Epub 2020 Nov 15.
Ref 4 [Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells]. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 National Cancer Institute Drug Dictionary (drug id 617379).
Ref 7 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278.
Ref 8 OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Cancer Lett. 2013 Jul 10;335(1):145-52. doi: 10.1016/j.canlet.2013.02.010. Epub 2013 Feb 10.
Ref 9 Clinical pipeline report, company report or official report of Purple Biotech.
Ref 10 Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies. Ann Oncol. 2015 May;26(5):998-1005. doi: 10.1093/annonc/mdv026. Epub 2015 Jan 21.
Ref 11 Clinical pipeline report, company report or official report of Gastroenterology.
Ref 12 Clinical pipeline report, company report or official report of Moleculin Biotech.
Ref 13 Napabucasin, a novel STAT3 inhibitor suppresses proliferation, invasion and stemness of glioblastoma cells. J Exp Clin Cancer Res. 2019 Jul 5;38(1):289. doi: 10.1186/s13046-019-1289-6.
Ref 14 Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma. Cancer Res Treat. 2019 Apr;51(2):510-518. doi: 10.4143/crt.2018.226. Epub 2018 Jun 13.
Ref 15 A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
Ref 16 In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
Ref 17 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.