m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03151
 [1]
Histone modification H3K9me2 G9a METTL3 Direct Enhancement m6A modification CASP1 CASP1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Caspase-1 (CASP1)
 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 PD-L1, CX3CR1 and Caspase-1 (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
Caspase-1 (CASP1) 14 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Belnacasan Phase 2 [2]
Synonyms
Second generation ICE inhibitors, Vertex; VRT-043198; VRT-43198; VX-765; VX-765)
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MOA Inhibitor
External Link
CID: 11398092
TTD: D0HK3N
 Compound Name PRALNACASAN Phase 2 [3]
Synonyms
VX-740; UNII-N986NI319S; 192755-52-5; N986NI319S; HMR3480/VX-740; Pralnacasan [USAN:INN]; HMR 3480; VX 470; Pralnacasan (USAN/INN); AC1L4A1A; SCHEMBL142187; GTPL6467; CHEMBL437526; DTXSID60172873; HMR3480; HMR-3480; BDBM50189360; AKOS030230853; DB04875; D08978; (4S,7S)-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carboxamide
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MOA Modulator
Activity IC50 = 3.6 nM
External Link
CID: 153270
TTD: D0U6WQ
DrugBank: DB04875
 Compound Name Nivocasan Phase 2 [4]
Synonyms
GS-9450; LB-84451
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MOA Modulator
External Link
CID: 11633038
TTD: D0Z2JF
DrugBank: DB12720
 Compound Name AC-201 Phase 2 [5]
MOA Inhibitor
External Link
TTD: D0WP2R
 Compound Name Ac-YVAD-FMK Patented [6]
MOA Inhibitor
External Link
TTD: D04KIH
 Compound Name Ac-YVAD-cmk Patented [6]
MOA Inhibitor
External Link
TTD: D07AVV
 Compound Name VE-16084 Terminated [7]
Synonyms
ICE inhibitors, Sanofi Winthrop; WIN-67694
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MOA Inhibitor
External Link
CID: 10009105
TTD: D0A3HF
 Compound Name L-709049 Terminated [8]
Synonyms
Ac-Yvad-cho; 143313-51-3; Acetyl-tyrosyl-valyl-alanyl-aspartal; Caspase-1 Inhibitor I; CHEMBL37630; Ac-Tyr-Val-Ala-Asp-H; IL-1beta Converting Enzyme (ICE) Inhibitor I; acetyl-Tyr-Val-Ala-Asp-aldehyde; N-acetyl-Tyr-Val-Ala-Asp-aldehyde; (3S)-3-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanamido]-3-methylbutanamido]propanamido]-4-oxobutanoic acid; Ac-Tyr-Val-Ala-Asp-Aldehyde; AC1NSK2K; SCHEMBL4349143; BDBM10355; MolPort-016-580-695; N-acetyl-Tyr-Val-Ala-Asp aldehyde; ZINC3915255; 1600AH; NCGC00167338-01
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MOA Inhibitor
Activity Ki = 0.7 nM
External Link
CID: 5311139
TTD: D0F9FA
 Compound Name SDZ-224-015 Terminated [9]
Synonyms
VE-13045
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MOA Modulator
External Link
CID: 101925102
TTD: D0K1CL
 Compound Name YVAD Investigative [10]
MOA Inhibitor
External Link
CID: 9847365
TTD: D0B3WF
 Compound Name Z-YVAD-CHO Investigative [11]
Synonyms
CHEMBL159822
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MOA Inhibitor
Activity Ki = 180 nM
External Link
CID: 44407073
TTD: D0P3XJ
 Compound Name Z-VAD-CHO Investigative [11]
Synonyms
CHEMBL320954; ZVAD-CHO; BDBM50176519; (S)-3-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-butyric acid
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MOA Inhibitor
Activity Ki = 8 nM
External Link
CID: 10112904
TTD: D0X8XO
 Compound Name Z-YVAD-FMK Investigative [12]
Synonyms
benzyloxycarbonyl-Tyr-Val-Ala-Asp(OMe)-fluoromethylketone; caspase-1 Inhibitor VI
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MOA Inhibitor
External Link
CID: 644196
TTD: D0YX4V
 Compound Name M826 Investigative [13]
Synonyms
compound 4sx
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MOA Inhibitor
External Link
CID: 9851134
TTD: D00YNW
Histone-lysine N-methyltransferase EHMT2 (EHMT2) 7 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name MS012 Preclinical [14]
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
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MOA Inhibitor
External Link
CID: 137348638
TTD: DJ1Q9B
 Compound Name BIX-01294 Preclinical [15]
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 [16]
Synonyms
A 366; A366
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MOA Inhibitor
Activity IC50 = 3 nM
External Link
CID: 76285486
TTD: D0C5EG
 Compound Name UNC0321 Investigative [17]
Synonyms
UNC-0321; UNC 0321
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MOA Inhibitor
Activity IC50 = 9000 nM
External Link
CID: 46901937
TTD: D0CX4W
 Compound Name BRD9539 Investigative [18]
Synonyms
BRD-9539; BRD 9539
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MOA Inhibitor
Activity IC50 = 1500 nM
External Link
CID: 73755260
TTD: D0RO9T
 Compound Name UNC0642 Investigative [19]
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 [20]
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
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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 (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydr... J Pharmacol Exp Ther. 2007 May;321(2):509-16.
Ref 3 Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46.
Ref 4 Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59.
Ref 7 Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
Ref 8 Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1). Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90.
Ref 9 Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme. Br J Pharmacol. 1995 Jun;115(4):601-6.
Ref 10 Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.
Ref 11 Tethering identifies fragment that yields potent inhibitors of human caspase-1. Bioorg Med Chem Lett. 2006 Feb;16(3):559-62.
Ref 12 Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. J Nutr. 2002 Jul;132(7):1812-8.
Ref 13 Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80. doi: 10.1016/j.bmcl.2004.12.006.
Ref 14 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 15 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 16 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 17 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 18 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 19 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 20 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.