m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03011
 [1]
m6A modification CBP CBP METTL14 Methylation : m6A sites Direct Inhibition Histone modification H3K27me3 CBP Downstream Gene
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP)
 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 27 trimethylation (H3K27me3) View Details
Crosstalk Relationship m6A  →  Histone modification Inhibition
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary The downregulation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (CBP) and p300 by METTL14 serves as a regulatory mechanism for the modulation of specific histone modifications, namely Histone H3 lysine 27 trimethylation (H3K27me3), H3K27ac, and H3K4me3. This regulatory action underscores the role of METTL14 in epigenetic control through the influence of m6A RNA methylation on histone modification patterns.
In-vivo Model Positive ES clones were used for injection into c57 blastocysts and generation of chimerical mice. To produce Mettl14f/+ mice, the chimeras were crossed with wild-type c57 for germ line transmission and then crossed with Atcb-Flpe transgenic mice (The Jackson Laboratory, # 003800) to remove FRT flanked selection cassette. Male Mettl14f/+ mice were crossed to female EIIa-Cre transgenic mice (The Jackson Laboratory, # 003724) to obtain Mettl14+/mice, and Mettl14+/ mice were intercrossed to obtain Mettl18-conventional knockout mice. Sex of embryos was determined.
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
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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
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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
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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 N(6)-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci. 2018 Feb;21(2):195-206. doi: 10.1038/s41593-017-0057-1. Epub 2018 Jan 15.
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).