m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03061
 [1]
Histone modification H3K18la CBP METTL3 Indirect Enhancement m6A modification ACSL4 ACSL4 YTHDC1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing protein 1 (YTHDC1) READER
 Regulator Info 
m6A Target Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator CREB-binding protein (CREBBP) WRITER View Details
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CREBBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway.
Responsed Disease Sepsis-associated lung injury ICD-11: NB30.4
 Disease Info 
In-vitro Model
MLE-12
 N.A. Mus musculus CVCL_3751
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
CREB-binding protein (CREBBP) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PRI-724 Phase 1/2 [2]
MOA Modulator
External Link
CID: 71509318
TTD: D0Q0ZY
DrugBank: DB15034
 Compound Name C 82 Phase 1/2 [3]
Synonyms
N-(4-Chlorophenyl)-2H-triazol-4-amine; SCHEMBL15831502; C82
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 75202656
TTD: D0DA5M
 Compound Name CCS1477 Phase 1/2 [4]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [5]
MOA Inhibitor
External Link
TTD: DT8IL6
 Compound Name Pyrrolo-pyrrolone derivative 6 Patented [6]
Synonyms
PMID26924192-Compound-39
    Click to Show/Hide
MOA Inhibitor
Activity IC50 < 91 nM
External Link
CID: 122553484
TTD: D0O9WQ
 Compound Name ischemin Investigative [7]
Synonyms
MS120
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MOA Inhibitor
Activity IC50 = 5000 nM
External Link
CID: 135566302
TTD: D00DXI
 Compound Name SGC-CBP30 Investigative [8]
Synonyms
1613695-14-9; (s)-4-(1-(2-(3-chloro-4-methoxyphenethyl)-5-(3,5-dimethylisoxazol-4-yl)-1h-benzo[d]imidazol-1-yl)propan-2-yl)morpholine; 2-[2-(3-chloro-4-methoxyphenyl)ethyl]-5-(dimethyl-1,2-oxazol-4-yl)-1-[(2S)-2-(morpholin-4-yl)propyl]-1H-1,3-benzodiazole; 2-[2-(3-Chloro-4-Methoxyphenyl)ethyl]-5-(3,5-Dimethyl-1,2-Oxazol-4-Yl)-1-[(2s)-2-(Morpholin-4-Yl)propyl]-1h-Benzimidazole; 2LO; C28H33ClN4O3; GTPL7529; SCHEMBL17512896; CHEMBL3622373; AOB4800; MolPort-035-395-859; BDBM188519; EX-A2159; ZINC96170456; s7256
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MOA Inhibitor
Activity IC50 = 30 nM
External Link
CID: 72201027
TTD: D03XXT
 Compound Name I-CBP112 Investigative [9]
Synonyms
1640282-31-0; I-CBP 112; CHEMBL3774655; 1-[7-(3,4-Dimethoxyphenyl)-9-[[(3S)-1-methylpiperidin-3-yl]methoxy]-2,3,4,5-tetrahydro-1,4-benzoxazepin-4-yl]propan-1-one; 1-[7-(3,4-dimethoxyphenyl)-9-{[(3S)-1-methylpiperidin-3-yl]methoxy}-2,3,4,5-tetrahydro-1,4-benzoxazepin-4-yl]propan-1-one; GTPL8236; SCHEMBL17620385; MolPort-035-765-871; EX-A2474; ZINC96024493; BDBM50151663; AKOS024458402; CS-6146; NCGC00350526-04; HY-19541; I-CBP112, &gt
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MOA Inhibitor
Activity IC50 = 440 nM
External Link
CID: 90488984
TTD: D0J3JI
References
Ref 1 Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury. Redox Biol. 2024 Aug;74:103194. doi: 10.1016/j.redox.2024.103194. Epub 2024 May 16.
Ref 2 Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14. doi: 10.1073/pnas.1001520107. Epub 2010 Jul 21.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 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 5 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 6 BET inhibitors in cancer therapeutics: a patent review. Expert Opin Ther Pat. 2016;26(4):505-22. doi: 10.1517/13543776.2016.1159299. Epub 2016 Mar 15.
Ref 7 A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes. Chem Biol. 2011 Apr 22;18(4):531-41. doi: 10.1016/j.chembiol.2010.12.021.
Ref 8 Bromodomains and their pharmacological inhibitors. ChemMedChem. 2014 Mar;9(3):438-64. doi: 10.1002/cmdc.201300434. Epub 2014 Feb 4.
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. (Target id: 2734).