m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03149
 [1]
Histone modification H3K9me2 G9a METTL3 Direct Enhancement m6A modification CD274 CD274 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Programmed cell death 1 ligand 1 (CD274/PD-L1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2) WRITER View Details
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2) View Details
Downstream Gene METTL3 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 EHMT2 promotes m6A methyltransferase activity of METTL3, which upregulates Programmed cell death 1 ligand 1 (CD274/PD-L1), CX3CR1 and CASP1, at translational/post-translational level by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET.
Responsed Disease Inflammatory response ICD-11: MG46
 Disease Info 
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
CD274 molecule (CD274) 55 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Avelumab Approved [2]
External Link
TTD: D0K7SX
 Compound Name Durvalumab Approved [3]
MOA Modulator
External Link
TTD: D0LS9E
 Compound Name RG-7446 Approved [4]
External Link
TTD: D0OZ4J
 Compound Name Bavencio Approved [5]
MOA Inhibitor
External Link
TTD: D0W8HN
 Compound Name Atezolizumab Approved [6]
External Link
TTD: D0YM2K
 Compound Name Sugemalimab Approved in China [7]
External Link
TTD: DDZ48Y
 Compound Name MEDI4736 Phase 3 [8]
MOA Modulator
External Link
TTD: D04RRZ
 Compound Name MPDL-3280A Phase 3 [9]
MOA Modulator
External Link
TTD: D0Y5IH
 Compound Name CS1001 Phase 3 [10]
External Link
TTD: D3MP1S
 Compound Name A167 Phase 3 [11]
Synonyms
KL-A167
    Click to Show/Hide
External Link
TTD: DI89WD
 Compound Name KN046 Phase 3 [12]
MOA Inhibitor
External Link
TTD: DLOQ25
 Compound Name Pidilizumab Phase 2 [13]
Synonyms
CT-011
    Click to Show/Hide
External Link
TTD: D09MRL
 Compound Name KN035 Phase 2 [14]
Synonyms
Envafolimab
    Click to Show/Hide
External Link
TTD: D0GF2R
 Compound Name CX-072 Phase 2 [15]
MOA Inhibitor
External Link
TTD: D0Z2BO
 Compound Name INCB86550 Phase 2 [16]
MOA Inhibitor
External Link
TTD: DKM79E
 Compound Name Bintrafusp alfa Phase 2 [17]
External Link
TTD: D5J3BL
 Compound Name M7824 Phase 2 [18]
MOA Inhibitor
External Link
TTD: D05FPZ
 Compound Name BGB-A333 Phase 1/2 [19]
External Link
TTD: DC5VW9
 Compound Name GS-4224 Phase 1/2 [20]
Synonyms
Methyl Pyridazine-4-carboxylate; 34231-77-1; PYRIDAZINE-4-CARBOXYLIC ACID METHYL ESTER; 4-PYRIDAZINECARBOXYLIC ACID, METHYL ESTER; MFCD09953488; ACMC-1AJNN; methyl 4-pyridazinecarboxylate; methylpyridazine-4-carboxylate; SCHEMBL1421640; DTXSID30498310; AMY24958; BCP22435; ANW-50355; ZINC12359421; AKOS015854403; Methyl pyridazine-4-carboxylate, 97%; AC-4414; CS-W003697; PB31452; 4-Pyridazinecarboxylic acid methyl ester; AK-48857; SY004472; AB0024323; DB-030309; FT-0717698; W5569; S-2990; J-522632
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 12439252
TTD: DS6VD0
 Compound Name NM21-1480 Phase 1/2 [21]
MOA Modulator
External Link
TTD: DUVH60
 Compound Name LY3300054 Phase 1 [18]
External Link
TTD: D08HSS
 Compound Name MSB2311 Phase 1 [14]
External Link
TTD: D0A8AU
 Compound Name Anti-PD-L1 Phase 1 [22]
Synonyms
BMS-936559
    Click to Show/Hide
External Link
TTD: D0KP9A
 Compound Name FAZ053 Phase 1 [15]
MOA Inhibitor
External Link
TTD: D0LU1O
 Compound Name Anti-PD-L1 CSR T cells Phase 1 [23]
MOA CAR-T-Cell-Therapy
External Link
TTD: D0W7UD
 Compound Name BMS-986189 Phase 1 [14]
MOA Inhibitor
External Link
TTD: D0X1GN
 Compound Name Cosibelimab Phase 1 [24]
Synonyms
CK-301/TG-1501
    Click to Show/Hide
External Link
TTD: D17URP
 Compound Name CA-170 Phase 1 [25]
MOA Inhibitor
External Link
TTD: D2Z6WF
 Compound Name PD-L1 t-haNK Phase 1 [26]
External Link
TTD: DH42RF
 Compound Name KD033 Phase 1 [27]
MOA Inhibitor
External Link
TTD: DJVR06
 Compound Name C-Met/PD-L1 CAR-T Cell Phase 1 [28]
MOA CAR-T-Cell-Therapy(Dual specific)
External Link
TTD: D03GTO
 Compound Name CA-170 Phase 1 [18]
Synonyms
3-Aminopyrrolidine dihydrochloride; 103831-11-4; pyrrolidin-3-amine dihydrochloride; 3-Pyrrolidinamine, dihydrochloride; 3-Aminopyrrolidine 2HCl; 3-Aminopyrrolidine diHCl; SCHEMBL555933; ACMC-2099s1; ACMC-2099s3; ACMC-20989g; 3-pyrrolidinamine dihydrochloride; CTK0H7226; DTXSID00583661; MolPort-002-343-989; NJPNCMOUEXEGBL-UHFFFAOYSA-N; 3-Amino-pyrrolidine dihydrochloride; KS-00000JI6; ACT01710; ANW-14978; SBB003982; ( -3-Aminopyrrolidine dihydrochloride; AKOS015844825; VP60158; AM85320; VP60228; TRA0055207; TRA0000843; TRA0097
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 16212596
TTD: D09PPU
 Compound Name FS118 Phase 1 [14]
External Link
TTD: D0XO9F
 Compound Name PF-07257876 Phase 1 [29]
External Link
TTD: D1A7OP
 Compound Name MCLA-145 Phase 1 [30]
MOA Agonist
External Link
TTD: D2QY0Z
 Compound Name GEN1046 Phase 1 [31]
MOA Agonist
External Link
TTD: D3HBJ1
 Compound Name ALPN-202 Phase 1 [32]
MOA Inhibitor
External Link
TTD: D82UVG
 Compound Name TAK-252 Phase 1 [33]
Synonyms
SL-279252
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MOA Agonist
External Link
TTD: D9SL1N
 Compound Name INBRX-105 Phase 1 [34]
MOA Inhibitor
External Link
TTD: DA1X5W
 Compound Name LY3415244 Phase 1 [35]
MOA Inhibitor
External Link
TTD: DC8HR6
 Compound Name A337 Phase 1 [11]
External Link
TTD: DL97UQ
 Compound Name IBI318 Phase 1 [36]
MOA Inhibitor
External Link
TTD: DX30BA
 Compound Name PMID30107136-Compound-Example2 Patented [37]
MOA Inhibitor
Activity IC50 = 150 nM
External Link
CID: 117941742
TTD: D0OK1S
 Compound Name PMID30107136-Compound-Example1 Patented [37]
MOA Inhibitor
Activity IC50 = 18 nM
External Link
CID: 117951478
TTD: D0WQ9X
 Compound Name PMID30247903-Compound-General structure7 Investigative [14]
Synonyms
PMID30247903Compound7
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MOA Inhibitor
External Link
TTD: D01TGF
 Compound Name CA-327 Investigative [14]
MOA Inhibitor
External Link
TTD: D04ILU
 Compound Name PMID30247903-Compound-General structure8 Investigative [14]
Synonyms
PMID30247903Compound8
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MOA Inhibitor
External Link
TTD: D04QGF
 Compound Name PMID30247903-Compound-General structure5 Investigative [14]
Synonyms
PMID30247903Compound5
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MOA Inhibitor
External Link
TTD: D07BOF
 Compound Name PMID30247903-Compound-General structure12 Investigative [14]
Synonyms
PMID30247903Compound12
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MOA Inhibitor
External Link
TTD: D09BYN
 Compound Name PMID30247903-Compound-General structure9 Investigative [14]
Synonyms
PMID30247903Compound9
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0GG6N
 Compound Name PMID30247903-Compound-General structure6 Investigative [14]
Synonyms
PMID30247903Compound6
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0TN4F
 Compound Name PMID30247903-Compound-General structure10 Investigative [14]
Synonyms
PMID30247903Compound10
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0XL3N
 Compound Name YH011 Investigative [38]
External Link
TTD: DA91UG
 Compound Name YH010 Investigative [39]
External Link
TTD: DBTI39
 Compound Name RG6084 Phase 1 [40]
External Link
TTD: DJX7K9
Histone-lysine N-methyltransferase EHMT2 (EHMT2) 7 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name MS012 Preclinical [41]
Synonyms
CHEMBL4086403; 2089617-83-2 (free base); N2-hexyl-6,7-dimethoxy-N4-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine; BDBM50501525; N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 137348638
TTD: DJ1Q9B
 Compound Name BIX-01294 Preclinical [42]
Synonyms
BIX01294; BIX 01294
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MOA Inhibitor
Activity IC50 = 67 nM
External Link
CID: 25150857
TTD: D06PPL
 Compound Name A-366 Preclinical [43]
Synonyms
A 366; A366
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 3 nM
External Link
CID: 76285486
TTD: D0C5EG
 Compound Name UNC0321 Investigative [44]
Synonyms
UNC-0321; UNC 0321
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 9000 nM
External Link
CID: 46901937
TTD: D0CX4W
 Compound Name BRD9539 Investigative [45]
Synonyms
BRD-9539; BRD 9539
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1500 nM
External Link
CID: 73755260
TTD: D0RO9T
 Compound Name UNC0642 Investigative [46]
Synonyms
1481677-78-4; UNC 0642; UNC-0642; CHEMBL2441082; 2-(4,4-Difluoro-1-piperidinyl)-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine; Barrett; GTPL7017; SCHEMBL17372593; AOB2595; MolPort-035-765-953; EX-A2241; BCP08266; ZINC96285772; BDBM50442103; AKOS024458509; SB19046; CS-5269; NCGC00189140-01; NCGC00189140-02; AS-16721; HY-13980; BC600721; AK547424; UNC0642, > KB-146019; J-008448
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MOA Inhibitor
Activity IC50 < 2.5 nM
External Link
CID: 53315878
TTD: D0BI4T
 Compound Name UNC0638 Investigative [47]
Synonyms
1255580-76-7; UNC-0638; UNC 0638; UNII-26A103L2FO; 2-Cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine; CHEMBL1231795; 26A103L2FO; 2-Cyclohexyl-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine; 1255517-77-1; 2-cyclohexyl-6-methoxy-N-[1-(propan-2-yl)piperidin-4-yl]-7-[3-(pyrrolidin-1-yl)propoxy]quinazolin-4-amine; 2-Cyclohexyl-N-(1-isopropyl-4-piperidinyl)-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 3.7 nM
External Link
CID: 46224516
TTD: D0GK7A
References
Ref 1 Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation. Cell Chem Biol. 2023 Dec 21;30(12):1525-1541.e7. doi: 10.1016/j.chembiol.2023.09.012. Epub 2023 Oct 19.
Ref 2 Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells. Cancer Immunol Res. 2015 Oct;3(10):1148-1157. doi: 10.1158/2326-6066.CIR-15-0059. Epub 2015 May 26.
Ref 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 4 PD-1 as a potential target in cancer therapy. Cancer Med. 2013 October; 2(5): 662-673.
Ref 5 ClinicalTrials.gov (NCT03403777) Avelumab in Refractory Testicular Germ Cell Cancer.. U.S. National Institutes of Health.
Ref 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 7 Sugemalimab: First Approval. Drugs. 2022 Apr;82(5):593-599.
Ref 8 National Cancer Institute Drug Dictionary (drug id 740856).
Ref 9 Targeted immunotherapy for non-small cell lung cancer. World J Clin Oncol. 2014 May 10; 5(2): 39-47.
Ref 10 GEMSTONE-301: a phase III clinical trial of CS1001 as consolidation therapy in patients with locally advanced/unresectable (stage III) non-small cell lung cancer (NSCLC) who did not have disease progression after prior concurrent/sequential chemoradiotherapy. Transl Lung Cancer Res. 2020 Oct;9(5):2008-2015. doi: 10.21037/tlcr-20-608.
Ref 11 Clinical pipeline report, company report or official report of Klus Pharma
Ref 12 Clinical pipeline report, company report or official report of Alphamab Oncology.
Ref 13 PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother. 2011 Jun;34(5):409-18. doi: 10.1097/CJI.0b013e31821ca6ce.
Ref 14 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 15 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 16 National Cancer Institute Drug Dictionary (drug name INCB086550).
Ref 17 Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-Beta and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial. J Thorac Oncol. 2020 Jul;15(7):1210-1222. doi: 10.1016/j.jtho.2020.03.003. Epub 2020 Mar 13.
Ref 18 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 19 Clinical pipeline report, company report or official report of BeiGene.
Ref 20 Clinical pipeline report, company report or official report of Gilead Sciences.
Ref 21 Clinical pipeline report, company report or official report of Numab Therapeutics.
Ref 22 Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
Ref 23 ClinicalTrials.gov (NCT02937844) Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
Ref 24 Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers
Ref 25 CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not?. Molecules. 2019 Aug 1;24(15):2804. doi: 10.3390/molecules24152804.
Ref 26 ClinicalTrials.gov (NCT04050709) QUILT 3.064: PD-L1 t-haNK In Subjects With Locally Advanced Or Metastatic Solid Cancers. U.S. National Institutes of Health.
Ref 27 Clinical pipeline report, company report or official report of Kadmon.
Ref 28 ClinicalTrials.gov (NCT03672305) Clinical Study on the Efficacy and Safety of c-Met/PD-L1 CAR-T Cell Injection in the Treatment of HCC
Ref 29 ClinicalTrials.gov (NCT04881045) A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS. U.S.National Institutes of Health.
Ref 30 Clinical pipeline report, company report or official report of Merus.
Ref 31 Clinical pipeline report, company report or official report of Genmab.
Ref 32 Clinical pipeline report, company report or official report of Alpine Immune Sciences.
Ref 33 Clinical pipeline report, company report or official report of Shattuck Labs.
Ref 34 Clinical pipeline report, company report or official report of Inhibrx.
Ref 35 Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors. Clin Cancer Res. 2021 May 15;27(10):2773-2781. doi: 10.1158/1078-0432.CCR-20-3716. Epub 2021 Jan 13.
Ref 36 Clinical pipeline report, company report or official report of Innovent.
Ref 37 A patent review on PD-1/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018). Expert Opin Ther Pat. 2018 Sep;28(9):665-678. doi: 10.1080/13543776.2018.1512706. Epub 2018 Sep 10.
Ref 38 Clinical pipeline report, company report or official report of Biocytogen
Ref 39 Clinical pipeline report, company report or official report of Biocytogen
Ref 40 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.
Ref 41 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 42 Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81. doi: 10.1016/j.molcel.2007.01.017.
Ref 43 Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett. 2014 Jan 2;5(2):205-9. doi: 10.1021/ml400496h. eCollection 2014 Feb 13.
Ref 44 Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. J Med Chem. 2010 Aug 12;53(15):5844-57. doi: 10.1021/jm100478y.
Ref 45 A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012 Jul 20;7(7):1152-7. doi: 10.1021/cb300139y. Epub 2012 Apr 30.
Ref 46 Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42. doi: 10.1021/jm401480r. Epub 2013 Oct 31.
Ref 47 A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. 2011 Jul 10;7(8):566-74. doi: 10.1038/nchembio.599.