m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03346
 [1], [2]
Histone modification H3K18la EP300 YTHDF2 Direct Enhancement m6A modification Stat1 Stat1 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Transcription factor ISGF-3 components p91/p84 (Stat1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene YTHDF2 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary Histone lactylation activates the transcription of YTHDF2 through p300-mediated Histone H3 lysine 18 lactylation (H3K18la) modification. In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model
 CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-F10 Mouse melanoma Mus musculus CVCL_0159
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [3]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
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MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [4]
MOA Inhibitor
External Link
TTD: DT8IL6
Transcription factor ISGF-3 components p91/p84 (Stat1) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Peptide analog 8 Patented [5]
Synonyms
PMID26394986-Compound-2
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0JF5K
 Compound Name Oxazole derivative 1 Patented [5]
Synonyms
PMID26394986-Compound-8
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 159000 nM
External Link
CID: 24768190
TTD: D0EZ6V
 Compound Name Peptidomimetic analog 5 Patented [5]
Synonyms
PMID26394986-Compound-7
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 42000 nM
External Link
CID: 9870708
TTD: D0XQ3F
 Compound Name Platinum IV complexe 1 Patented [5]
Synonyms
PMID26394986-Compound-69
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MOA Inhibitor
Activity IC50 = 4100 nM
External Link
TTD: D01BVU
 Compound Name PMID26394986-Compound-10 Patented [5]
MOA Inhibitor
Activity IC50 > 160000 nM
External Link
CID: 252682
TTD: D0TU0X
 Compound Name AVT-02 UE Discontinued in Phase 2 [6]
MOA Inhibitor
External Link
TTD: D03WRN
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [7]
Synonyms
INCMGA0012; Retifanlimab
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External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [8]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
TTD: D0C9ET
 Compound Name Regorafenib Approved [9]
Synonyms
755037-03-7; BAY 73-4506; Regorafenibum; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; BAY73-4506; Regorafenib (BAY 73-4506); UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); BAY73-4506 hydrochloride; Regorafenib [USAN:INN]
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External Link
CID: 11167602
TTD: D09GDD
DrugBank: DB08896
 Compound Name Bevacizumab Approved [10]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
TTD: D04KBL
 Compound Name SYM-004 Phase 3 [10]
Synonyms
Chimeric IgG1 antibody 1024 (cancer), Symphogen; Chimeric IgG1 antibody 992 (cancer), Symphogen; Chimeric IgG1 antibodies992 + 1024 (cancer), Symphogen
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External Link
TTD: D0CR8H
 Compound Name Bevacizumab + Erlotinib Phase 3 [11]
External Link
TTD: D09BKY
 Compound Name CPI-613 Phase 3 [10]
Synonyms
95809-78-2; 6,8-bis(benzylthio)octanoic acid; CPI 613; MLS006010202; SCHEMBL1062218; 6,8-Bis(benzylsulfanyl)octanoic acid; Octanoic acid, 6,8-bis((phenylmethyl)thio)-; Octanoic acid, 6,8-bis[(phenylMethyl)thio]-; 6,8-Bis[(phenylmethyl)thio]octanoic acid; CPI613; CHEMBL3186849; QCR-193; AOB1058; MolPort-023-219-128; HMS3656L06; C22H28O2S2; BCP04663; EX-A2043; s2776; AKOS025142095; BCP9000552; DB12109; RL06062; CS-0961; NCGC00344764-01; SMR004701300; AS-16613; BC261916; AK174899; HY-15453; BCP0726000030; KB-293127; AB0035874
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External Link
CID: 24770514
TTD: D07NVI
DrugBank: DB12109
 Compound Name Bevacizumab Approved [8]
External Link
TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [12]
Synonyms
AlloStim (TN)
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External Link
TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [13]
External Link
TTD: DVX3H0
 Compound Name CV301 Phase 2 [14]
External Link
TTD: D9LT5G
 Compound Name Efatutazone Phase 2 [15]
Synonyms
Inolitazone; 223132-37-4; 5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-2,4-Thiazolidinedione; Efatutazone [INN]; RS5444; CS-7017; SCHEMBL3246054; CHEMBL3545280; JCYNMRJCUYVDBC-UHFFFAOYSA-N; Efatutazone;CS-7017;RS5444; BCP07478; AKOS030526729; DB11894; CS-0778; KB-77905; DA-07988; HY-14792; QC-10456; 4CA-1384; FT-0737589; 5-[4-[6-(4-amino-3 ,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione
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External Link
CID: 9832447
TTD: D0Y8NZ
DrugBank: DB11894
 Compound Name LOR-2040 Phase 2 [16]
External Link
TTD: D0I7NG
 Compound Name RG7221 Phase 2 [17]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [18]
Synonyms
EZN-2208
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External Link
CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [19]
External Link
TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [20]
External Link
TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [21]
External Link
CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [17]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [22]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [10]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [23]
External Link
TTD: D0E2CQ
 Compound Name Nimesulide Terminated [24]
Synonyms
51803-78-2; N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide; Mesulid; Flogovital; Sulidene; Nimed; R-805; 4-NITRO-2-PHENOXYMETHANESULFONANILIDE; Nisulid; Nimesulidum [INN-Latin]; Nimesulida [INN-Spanish]; R 805; UNII-V4TKW1454M; 4-Nitro-2-phenoxy-methanesulfonanilide; 4'-Nitro-2'-phenoxymethanesulfonanilide; Methanesulfonamide, N-(4-nitro-2-phenoxyphenyl)-; EINECS 257-431-4; 4'-Nitro-2'-phenoxymethansulfonanilid; BRN 2421175; CHEMBL56367; MLS000069680; V4TKW1454M; Methanesulfonanilide, 4'-nitro-2'-phenoxy-; CHEBI:44445; Dulanermin
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External Link
CID: 4495
TTD: D0C0JT
DrugBank: DB04743
 Compound Name Saracatinib Phase 2 [25]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [26]
External Link
CID: 91865905
TTD: D05IAN
References
Ref 1 The m6A methyltransferase METTL3 modifies Kcnk6 promoting on inflammation associated carcinogenesis is essential for colon homeostasis and defense system through histone lactylation dependent YTHDF2 binding. Int Rev Immunol. 2025;44(1):1-16. doi: 10.1080/08830185.2024.2401358. Epub 2024 Sep 13.
Ref 2 m(6) A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy. EMBO J. 2020 Oct 15;39(20):e104514. doi: 10.15252/embj.2020104514. Epub 2020 Sep 23.
Ref 3 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 4 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 5 A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
Ref 6 Avontec Announces Results of a Multiple Dose Clinical Phase I Study with Its Drug Candidate AVT-02 UE Ointment After Topical Treatment in Male Healthy Volunteers. Avontec. 2008.
Ref 7 Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway.J Med Chem. 2019 Feb 28;62(4):1715-1730.
Ref 8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 9 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: 5891).
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 13 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 14 ClinicalTrials.gov (NCT03547999) A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC. U.S. National Institutes of Health.
Ref 15 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 16 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 18 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT00909740) A Study of the Safety and Pharmacokinetics of MEGF0444A Administered to Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 20 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 21 ClinicalTrials.gov (NCT04660812) An Open Label Study Evaluating the Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 22 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 23 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029052)
Ref 24 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 25 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 26 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.