m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03013
 [1]
m6A modification EZH2 EZH2 METTL3 Methylation : m6A sites Direct Enhancement Histone modification H3K27me3 Ezh2 Downstream Gene
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Histone-lysine N-methyltransferase EZH2 (EZH2)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase EZH2 (EZH2) WRITER View Details
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3) View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary m6A was present on the transcripts of histone methyltransferase Histone-lysine N-methyltransferase EZH2 (EZH2), and its reduction upon METTL3 knockdown decreased both Ezh2 protein expression and consequent Histone H3 lysine 27 trimethylation (H3K27me3) levels. The defects of neurogenesis and neuronal development induced by Mettl3-depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
In-vivo Model Mice were housed in standard conditions in the Laboratory Animal Center of Zhejiang University on a 12 h light/dark schedule with free access to food and water. The pregnant mice were purchased from Shanghai SLAC Laboratory Animal Company, China. All animal experiments were conducted according to protocols approved by the Zhejiang University Animal Care and Use Committee.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone-lysine N-methyltransferase EZH2 (EZH2) 74 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Tazemetostat Approved [2]
Synonyms
EPZ-6438; 1403254-99-8; EPZ6438; UNII-Q40W93WPE1; N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide; Q40W93WPE1; EPZ 6438; E7438; (1,1'-Biphenyl)-3-carboxamide, N-((1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(4-morpholinylmethyl)-
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 2.5 nM
External Link
CID: 66558664
TTD: D00EQL
DrugBank: DB12887
 Compound Name DS-3201b Phase 2 [3]
Synonyms
Valemetostat; 1809336-39-7; UNII-60RD0234VE; 60RD0234VE; 1809336-39-7 (free base); DS-3201; (2R)-7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide; Valemetostat 2HCl; Valemetostat [INN]; Valemetostat (DS-3201); CHEMBL4597193; EZH1/2 inhibitor DS-3201; SCHEMBL18393626; SCHEMBL18393627; SCHEMBL18639210; EX-A3423; DS3201; NSC813381; s8926; NSC-813381; HY-109108; CS-0039740; D11551
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 126481870
TTD: DNM79H
 Compound Name CPI-1205 Phase 1/2 [4]
Synonyms
HPODOLXTMDHLLC-QGZVFWFLSA-N; 1621862-70-1; UNII-455J2479FY; CPI1205; CPI 1205; 455J2479FY; (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide; GTPL9115; SCHEMBL17329268; MolPort-044-560-382; KS-000006BA; EX-A1068; s8353; AKOS030628484; ZINC220982768; CS-7648; compound 13 [PMID: 27739677]; HY-100021; J3.556.402K; N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-methyl-1-[(1R)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 78320408
TTD: D0E6AG
DrugBank: DB14581
 Compound Name SHR2554 Phase 1/2 [5]
MOA Inhibitor
External Link
TTD: DM5X0L
 Compound Name CPI-0209 Phase 1/2 [6]
MOA Inhibitor
External Link
TTD: DXL38G
 Compound Name GSK2816126 Phase 1 [7]
Synonyms
GSK 126; GSK-126
    Click to Show/Hide
MOA Modulator
Activity Ki = 0.5 nM
External Link
CID: 68210102
TTD: D05FIJ
 Compound Name PF-06821497 Phase 1 [8]
Synonyms
UNII-S4L4MM20B6; S4L4MM20B6; CHEMBL4080228; PF06821497; 1844849-10-0; 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one; SCHEMBL17330426; GTPL10516; BDBM50246967; NSC800019; DB14799; HY-101571A; NSC-800019; compound 23a [PMID: 29211475]; CS-0092626; Q29209799; 1(2H)-Isoquinolinone, 5,8-dichloro-2-((1,2-dihydro-4-methoxy-6-methyl-2-oxo-3-pyridinyl)methyl)-3,4-dihydro-7-((R)-methoxy-3-oxetanylmethyl)-; 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1-one; CJD
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 118572065
TTD: DI1L7M
DrugBank: DB14799
 Compound Name DS-3201 Phase 1 [4]
Synonyms
QTGYNKYZRZATJB-UHFFFAOYSA-N; 701899-63-0; 2-(2-(2-Methyl-1H-imidazol-5-yl)ethyl)isoindoline-1,3-dione; 2-(2-(2-Methyl-1H-imidazol-5-yl)-ethyl)isoindoline-1,3-dione; SCHEMBL7743461; MolPort-035-945-474; MolPort-035-690-353; ZINC98086069; AKOS024459002; AKOS024262663; MCULE-2708350770; FCH4077443; AK158834; AX8292467; ST2403812; 2-[2-(2-methyl-1H-imidazol-5-yl)ethyl]-2,3-dihydro-1H-isoindole-1,3-dione
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 22627096
TTD: D0LG8T
 Compound Name HH2853 Phase 1 [9]
MOA Inhibitor
External Link
TTD: D6EU7R
 Compound Name PMID28394193-Compound-33 Patented [10]
MOA Inhibitor
Activity IC50 = 100 nM
External Link
CID: 121305270
TTD: D03MYI
 Compound Name PMID28394193-Compound-Figure3bI Patented [10]
MOA Inhibitor
External Link
TTD: D04PCW
 Compound Name PMID28394193-Compound-35 Patented [10]
MOA Inhibitor
Activity IC50 = 10 nM
External Link
TTD: D05MAR
 Compound Name PMID28394193-Compound-54 Patented [10]
MOA Inhibitor
External Link
TTD: D07CZI
 Compound Name PMID28394193-Compound-24 Patented [10]
MOA Inhibitor
Activity IC50 < 1000 nM
External Link
CID: 117807842
TTD: D08MXO
 Compound Name PMID28394193-Compound-27 Patented [10]
MOA Inhibitor
Activity IC50 < 1000 nM
External Link
CID: 76684269
TTD: D09GFF
 Compound Name PMID28394193-Compound-25 Patented [10]
MOA Inhibitor
Activity IC50 < 1000 nM
External Link
CID: 117807842
TTD: D09PQQ
 Compound Name PMID28394193-Compound-50 Patented [10]
MOA Inhibitor
Activity IC50 > 1 nM; IC50 < 2 nM; Ki > 0.01 nM; Ki < 0.04 nM
External Link
CID: 118580552
TTD: D0A0VH
 Compound Name PMID28394193-Compound-47 Patented [10]
MOA Inhibitor
Activity IC50 = 2 nM; Ki < 1 nM
External Link
CID: 118616529
TTD: D0B4TX
 Compound Name PMID28394193-Compound-21 Patented [10]
MOA Inhibitor
External Link
TTD: D0BL8W
 Compound Name PMID28394193-Compound-41 Patented [10]
MOA Inhibitor
External Link
CID: 118101320
TTD: D0BT6Y
 Compound Name PMID28394193-Compound-53 Patented [10]
MOA Inhibitor
Activity IC50 = 80 nM
External Link
CID: 121322599
TTD: D0CH4O
 Compound Name PMID28394193-Compound-Figure5aVIII Patented [10]
MOA Inhibitor
External Link
TTD: D0D1QD
 Compound Name PMID28394193-Compound-38 Patented [10]
MOA Inhibitor
External Link
CID: 78320108
TTD: D0DQ6N
 Compound Name PMID28394193-Compound-51 Patented [10]
MOA Inhibitor
Activity IC50 > 1 nM; IC50 < 2 nM; Ki > 0.01 nM; Ki < 0.04 nM
External Link
CID: 118580509
TTD: D0FC9J
 Compound Name PMID28394193-Compound-31 Patented [10]
MOA Inhibitor
Activity IC50 = 20 nM
External Link
TTD: D0FI3A
 Compound Name PMID28394193-Compound-42 Patented [10]
MOA Inhibitor
External Link
CID: 118096643
TTD: D0H4HR
 Compound Name PMID28394193-Compound-15 Patented [10]
MOA Inhibitor
External Link
TTD: D0KR2T
 Compound Name PMID28394193-Compound-52 Patented [10]
MOA Inhibitor
Activity IC50 > 1 nM; IC50 < 2 nM; Ki > 0.01 nM; Ki < 0.04 nM
External Link
CID: 118580510
TTD: D0LR5O
 Compound Name PMID28394193-Compound-32 Patented [10]
MOA Inhibitor
Activity IC50 = 500 nM
External Link
TTD: D0M1TG
 Compound Name PMID28394193-Compound-23 Patented [10]
MOA Inhibitor
Activity IC50 < 1000 nM
External Link
CID: 117807623
TTD: D0M9BY
 Compound Name PMID28394193-Compound-29 Patented [10]
MOA Inhibitor
Activity IC50 = 100 nM
External Link
TTD: D0MH8G
 Compound Name PMID28394193-Compound-30 Patented [10]
MOA Inhibitor
Activity IC50 = 16 nM
External Link
TTD: D0MO2X
 Compound Name PMID28394193-Compound-39 Patented [10]
MOA Inhibitor
External Link
TTD: D0MZ8D
 Compound Name PMID28394193-Compound-49 Patented [10]
MOA Inhibitor
Activity IC50 > 1 nM; IC50 < 2 nM; Ki > 0.01 nM; Ki < 0.04 nM
External Link
CID: 118572078
TTD: D0PB6T
 Compound Name PMID28394193-Compound-43 Patented [10]
MOA Inhibitor
External Link
CID: 118096796
TTD: D0PI5O
 Compound Name PMID28394193-Compound-40 Patented [10]
MOA Inhibitor
External Link
CID: 118095598
TTD: D0QH1J
 Compound Name PMID28394193-Compound-Figure3bIII Patented [10]
MOA Inhibitor
External Link
TTD: D0R2TQ
 Compound Name PMID28394193-Compound-36 Patented [10]
MOA Inhibitor
Activity IC50 = 316 nM
External Link
TTD: D0RD5P
 Compound Name PMID28394193-Compound-28 Patented [10]
MOA Inhibitor
Activity IC50 = 32 nM
External Link
CID: 91884579
TTD: D0S4OP
 Compound Name PMID28394193-Compound-22 Patented [10]
MOA Inhibitor
External Link
TTD: D0SQ1R
 Compound Name PMID28394193-Compound-18 Patented [10]
MOA Inhibitor
External Link
TTD: D0SY6P
 Compound Name PMID28394193-Compound-16 Patented [10]
MOA Inhibitor
External Link
TTD: D0T8QL
 Compound Name PMID28394193-Compound-44 Patented [10]
MOA Inhibitor
External Link
CID: 118096614
TTD: D0U9OH
 Compound Name PMID28394193-Compound-20 Patented [10]
MOA Inhibitor
External Link
TTD: D0UG5O
 Compound Name PMID28394193-Compound-19 Patented [10]
MOA Inhibitor
External Link
TTD: D0VF0M
 Compound Name PMID28394193-Compound-37 Patented [10]
MOA Inhibitor
External Link
CID: 78320107
TTD: D0W2KL
 Compound Name PMID28394193-Compound-Figure3bII Patented [10]
MOA Inhibitor
External Link
TTD: D0W4MW
 Compound Name PMID28394193-Compound-26 Patented [10]
MOA Inhibitor
Activity IC50 < 1000 nM
External Link
CID: 75203283
TTD: D0Z0NC
 Compound Name PMID28394193-Compound-17 Patented [10]
MOA Inhibitor
External Link
TTD: D0Z0QS
 Compound Name PMID28394193-Compound-34 Patented [10]
MOA Inhibitor
Activity IC50 = 100 nM
External Link
TTD: D0Z7GN
 Compound Name PMID28394193-Compound-56 Patented [10]
MOA Inhibitor
Activity IC50 = 0.93 nM
External Link
TTD: D01PZZ
 Compound Name PMID28394193-Compound-46 Patented [10]
MOA Inhibitor
Activity IC50 = 5 nM
External Link
CID: 102593999
TTD: D0D4UH
 Compound Name PMID28394193-Compound-57 Patented [10]
MOA Inhibitor
Activity IC50 = 6.45 nM
External Link
TTD: D0G1JR
 Compound Name PMID28394193-Compound-14 Patented [10]
MOA Inhibitor
Activity IC50 = 21900 nM
External Link
CID: 90467336
TTD: D0GT7A
 Compound Name PMID28394193-Compound-12 Patented [10]
MOA Inhibitor
Activity IC50 < 10 nM
External Link
TTD: D0H8VN
 Compound Name PMID26882240-Compound-1 Patented [11]
MOA Inhibitor
External Link
CID: 5712
TTD: D0L1TA
 Compound Name PMID28394193-Compound-55 Patented [10]
MOA Inhibitor
Activity IC50 = 8.13 nM
External Link
TTD: D0M4LK
 Compound Name PMID28394193-Compound-45 Patented [10]
MOA Inhibitor
Activity IC50 = 168000 nM
External Link
CID: 118607675
TTD: D0M8AA
 Compound Name PMID28394193-Compound-13 Patented [10]
MOA Inhibitor
Activity IC50 = 1470 nM
External Link
CID: 86765324
TTD: D0TA4N
 Compound Name EPZ005687 Investigative [12]
Synonyms
EPZ-005687; EPZ 005687
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 60160561
TTD: D02BBA
 Compound Name EI1 Investigative [13]
Synonyms
KB-145943
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 72199293
TTD: D02CIT
 Compound Name UNC1999 Investigative [14]
Synonyms
UNC 1999; UNC-1999
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 72551585
TTD: D02YXP
 Compound Name MS1943 Investigative [5]
Synonyms
2225938-17-8; SCHEMBL21271666; EX-A3962; s8918; HY-133129; CS-0112146; 6-(6-(4-(2-(2-((3r,5r,7r)-adamantan-1-yl)acetamido)ethyl)piperazin-1-yl)pyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide; 6-(6-(4-(2-(2-(Adamantan-1-yl)acetamido)ethyl)piperazin-1-yl)pyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide
    Click to Show/Hide
MOA Degrader
External Link
CID: 139211327
TTD: D65IMT
 Compound Name GSK343 Investigative [15]
Synonyms
compound 6 [PMID 24900432]; GSK 343
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 174 nM
External Link
CID: 71268957
TTD: D02TVQ
 Compound Name PMID28394193-Compound-11 Patented [16]
External Link
TTD: D0MH5C
 Compound Name PMID28394193-Compound-10 Patented [16]
External Link
TTD: D0MZ9P
 Compound Name PMID28394193-Compound-14 Patented [10]
MOA Inhibitor
Activity IC50 = 21900 nM
External Link
CID: 90467336
TTD: D0GT7A
 Compound Name PMID28394193-Compound-12 Patented [10]
MOA Inhibitor
Activity IC50 < 10 nM
External Link
TTD: D0H8VN
 Compound Name PMID28394193-Compound-13 Patented [10]
MOA Inhibitor
Activity IC50 = 1470 nM
External Link
CID: 86765324
TTD: D0TA4N
 Compound Name PMID28394193-Compound-56 Patented [10]
MOA Inhibitor
Activity IC50 = 0.93 nM
External Link
TTD: D01PZZ
 Compound Name PMID28394193-Compound-46 Patented [10]
MOA Inhibitor
Activity IC50 = 5 nM
External Link
CID: 102593999
TTD: D0D4UH
 Compound Name PMID28394193-Compound-57 Patented [10]
MOA Inhibitor
Activity IC50 = 6.45 nM
External Link
TTD: D0G1JR
 Compound Name PMID28394193-Compound-55 Patented [10]
MOA Inhibitor
Activity IC50 = 8.13 nM
External Link
TTD: D0M4LK
 Compound Name PMID28394193-Compound-45 Patented [10]
MOA Inhibitor
Activity IC50 = 168000 nM
External Link
CID: 118607675
TTD: D0M8AA
References
Ref 1 m(6)A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2. Genomics Proteomics Bioinformatics. 2019 Apr;17(2):154-168. doi: 10.1016/j.gpb.2018.12.007. Epub 2019 May 30.
Ref 2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
Ref 3 Development of new agents for peripheral T-cell lymphoma. Expert Opin Biol Ther. 2019 Mar;19(3):197-209. doi: 10.1080/14712598.2019.1572746. Epub 2019 Jan 29.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286. doi: 10.1038/s41573-020-00108-x. Epub 2021 Jan 19.
Ref 6 ClinicalTrials.gov (NCT04104776) A Study of CPI-0209 in Patients With Advanced Tumors. U.S. National Institutes of Health.
Ref 7 National Cancer Institute Drug Dictionary (drug id 756211).
Ref 8 Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J Med Chem. 2018 Feb 8;61(3):650-665. doi: 10.1021/acs.jmedchem.7b01375. Epub 2017 Dec 27.
Ref 9 Clinical pipeline report, company report or official report of HaiHe Biopharma.
Ref 10 EZH2 inhibitors: a patent review (2014-2016). Expert Opin Ther Pat. 2017 Jul;27(7):797-813. doi: 10.1080/13543776.2017.1316976. Epub 2017 Apr 20.
Ref 11 Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015). Expert Opin Ther Pat. 2016;26(3):309-22. doi: 10.1517/13543776.2016.1146252. Epub 2016 Feb 16.
Ref 12 A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6. doi: 10.1038/nchembio.1084. Epub 2012 Sep 30.
Ref 13 Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21360-5. doi: 10.1073/pnas.1210371110. Epub 2012 Dec 10.
Ref 14 An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324-34. doi: 10.1021/cb400133j. Epub 2013 Apr 24.
Ref 15 Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6. doi: 10.1021/ml3003346. eCollection 2012 Dec 13.
Ref 16 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.