m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03373
 [1], [2]
Histone modification H3K18la Epigenetic Regulator AP001885.4 Indirect Enhancement m6A modification NOTCH1 NOTCH1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Neurogenic locus notch homolog protein 1 (NOTCH1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene AP001885.4 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism Histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated c-myc and promoted cell proliferation METTL3-catalyzed m6A modification promotes Neurogenic locus notch homolog protein 1 (NOTCH1) expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells.
Responsed Disease Esophageal Squamous Cell Carcinoma ICD-11: 2B70.1
 Disease Info 
Cell Process mRNA stability
Cell proliferation
In-vitro Model
 TE-9 Esophageal squamous cell carcinoma Homo sapiens CVCL_1767
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In-vivo Model For induction of ESCC, 4-week-old mice were treated with drinking water containing 50 ug/mL 4NQO (Sigma-Aldrich, USA) for 16 weeks and then given normal drinking water for another 4-5 weeks. Cre was activated by the intraperitoneal injection of tamoxifen (Sigma-Aldrich, USA) at a dose of 9 mg per 40 g body weight every other day for a total of three injections. For tumor measurement, mice were sacrificed, and the esophagus was dissected immediately. The surface areas of tumors were measured as described previously.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Neurogenic locus notch homolog protein 1 (NOTCH1) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name LY3039478 Phase 1/2 [3]
Synonyms
Crenigacestat; 1421438-81-4; LY-3039478; UNII-923X28214S; 4,4,4-Trifluoro-N-((S)-1-(((S)-5-(2-hydroxyethyl)-6-oxo-6,7-dihydro-5H-benzo[d]pyrido[2,3-b]azepin-7-yl)amino)-1-oxopropan-2-yl)butanamide; 923X28214S; butanamide, n-[(1s)-2-[[(7s)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5h-pyrido[3,2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4,4,4-trifluoro-; Butanamide, N-((1S)-2-(((7S)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5H-pyrido(3,2-a)(3)benzazepin-7-yl)amino)-1-methyl-2-oxoethyl)-4,4,4-trifluoro-
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MOA Inhibitor
External Link
CID: 71236992
TTD: D08WOW
DrugBank: DB12050
 Compound Name OMP-52M51 Phase 1 [4]
External Link
TTD: D0X3YY
2B70: Esophageal cancer 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Pembrolizumab Approved [3]
External Link
TTD: D08ANZ
 Compound Name Nivolumab Approved [3]
External Link
TTD: D00GOV
 Compound Name Claudiximab Phase 3 [5]
Synonyms
IMAB-362; Anti-GC182 mAbs (cancer), Ganymed; Anti-GC182 monoclonal antibodies (cancer), Ganymed; Anti-CLDN18-2 mAbs (cancer), Ganymed; Anti-CLDN18-2 monoclonal antibodies (cancer), Ganymed
    Click to Show/Hide
External Link
TTD: D0B3ZC
 Compound Name Golnerminogene pradenovac Phase 3 [6]
Synonyms
TNFerade (TN)
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External Link
TTD: D03QBT
 Compound Name DKN-01 Phase 2 [7]
External Link
TTD: DMF73Z
 Compound Name Pegamotecan Phase 2 [8]
Synonyms
Prothecan; EZ-246; PEG-camptothecin; PEG-camptothecin, Enzon; Polyethylene glycol-camptothecin, Enzon
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External Link
CID: 11297617
TTD: D0D4CX
 Compound Name APR-246 Phase 2 [3]
Synonyms
Eprenetapopt
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External Link
CID: 52918385
TTD: D03XTY
DrugBank: DB11684
 Compound Name Opdivo + Yervoy Phase 3 [3]
External Link
TTD: D02VYE
 Compound Name Anti-NY-ESO-1 CAR-T cells Phase 1/2 [9]
External Link
TTD: D0LJ2S
 Compound Name Anti-MUC1 CAR-T cells Phase 1/2 [10]
External Link
TTD: D09KWN
 Compound Name CAR-T Cells targeting EpCAM Phase 1/2 [11]
External Link
TTD: D08QYW
 Compound Name PCA062 Phase 1 [3]
External Link
TTD: D09WSR
 Compound Name Cellspan esophageal implant Clinical trial [3]
External Link
TTD: D0SW1D
 Compound Name PKI166 Discontinued in Phase 2 [12]
Synonyms
PKI-166; CGP-75166; 187724-61-4; NVP-PKI166; CHEMBL1914653; AC1OCFE0; UNII-9RIE5HW38P; 9RIE5HW38P; SCHEMBL177814; GTPL7642; CHEMBL1963502; ZINC23255; AOB1619; PKI-75166; BDBM50358046; NCGC00387215-02; AS-16676; KB-275097; PKI-166, > 4-[4-[[(1R)-1-phenylethyl]amino]-7H-pyrrolo[4,5-e]pyrimidin-6-yl]phenol
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External Link
CID: 6918403
TTD: D07GFF
 Compound Name Ramorelix Discontinued in Phase 1 [13]
Synonyms
Hoe-013
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External Link
CID: 25077455
TTD: D0S6AQ
References
Ref 1 AP001885.4 promotes the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc. Anim Cells Syst (Seoul). 2024 Nov 1;28(1):536-550. doi: 10.1080/19768354.2024.2417458. eCollection 2024.
Ref 2 METTL3-mediated m(6)A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway. Mol Ther Nucleic Acids. 2021 Jul 21;26:333-346. doi: 10.1016/j.omtn.2021.07.007. eCollection 2021 Dec 3.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 National Cancer Institute Drug Dictionary (drug id 741867).
Ref 5 ClinicalTrials.gov (NCT01197885) Efficacy and Safety Study of Multiple Doses of IMAB362 in Patients With Advanced Gastroesophageal Cancer. U.S. National Institutes of Health.
Ref 6 ClinicalTrials.gov (NCT00051467) A Study of TNFerade Biologic With 5-FU and Radiation Therapy for First-Line Treatment of Unresectable Locally Advanced Pancreatic Cancer. U.S. National Institutes of Health.
Ref 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 8 ClinicalTrials.gov (NCT00080002) Efficacy of Pegamotecan (PEG-Camptothecin) in Localized or Metastatic Cancer of the Stomach or Gastroesophageal Junction. U.S. National Institutes of Health.
Ref 9 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
Ref 10 ClinicalTrials.gov (NCT03706326) CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Ref 11 ClinicalTrials.gov (NCT03013712) A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer
Ref 12 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7642).
Ref 13 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008630)