m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03200
 [1]
m6A modification EZH2 EZH2 IGF2BP1 : m6A sites Direct Enhancement Histone modification H3K27me3 EZH2 Downstream Gene
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 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 IGF2BP1 promotes neuroendocrine tumor cell proliferation by stabilizing the mRNA of Histone-lysine N-methyltransferase EZH2 (EZH2), the catalytic subunit of PRC2, which represses gene expression by tri-methylation of Histone H3 lysine 27 trimethylation (H3K27me3).
Responsed Disease Neuroendocrine neoplasms ICD-11: 2D4Y
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Increase in G1 and sub-G1 phases
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)-
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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
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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
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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
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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
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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
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MOA Degrader
External Link
CID: 139211327
TTD: D65IMT
 Compound Name GSK343 Investigative [15]
Synonyms
compound 6 [PMID 24900432]; GSK 343
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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 IGF2BP1 Promotes Proliferation of Neuroendocrine Neoplasms by Post-Transcriptional Enhancement of EZH2. Cancers (Basel). 2022 Apr 24;14(9):2121. doi: 10.3390/cancers14092121.
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.