Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05161
[1]
Non-coding RNA miR-1208 METTL3  lncRNA       miRNA   circRNA Direct Inhibition m6A modification NLRP3 NLRP3 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-1208 microRNA View Details
Regulated Target Methyltransferase-like protein 3 (METTL3) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary hucMSCs-EVs inhibited the secretion of pro-inflammatory factors and the degradation of cartilage ECM after lowering the m6A level of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA with hsa-miR-1208 targeting combined with METTL3, thereby alleviating OA progression in mice and providing a novel therapy for clinical OA treatment.
Responsed Disease Osteoarthritis ICD-11: FA05
In-vitro Model
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) 4 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Dapansutrile Phase 2 [2]
Synonyms
54863-37-5; OLT1177; UNII-2Z03364G96; 2Z03364G96; Dapansutrile [INN]; Dapansutrile [USAN:INN]; Dapansutrile (USAN/INN); 3-Methylsulfonylpropionitrile; 3-methanesulfonylpropanenitrile; 3-methylsulphonyl-propionitrile; SCHEMBL9934796; CHEMBL3989943; LQFRYKBDZNPJSW-UHFFFAOYSA-N; MolPort-008-545-498; ZINC32005410; Propanenitrile, 3-(methylsulfonyl)-; AKOS010140086; D10920; Z2719319073
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MOA Inhibitor
External Link
 Compound Name BMS-986299 Phase 1 [3]
MOA Agonist
External Link
 Compound Name Selnoflast Phase 1 [4]
Synonyms
1-(1-ethylpiperidin-4-yl)sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea; 1-Ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-4-piperidinesulfonamide; 1-ethyl-N-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]piperidine-4-sulfonamide; 2260969-36-4; 4-Piperidinesulfonamide, 1-ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-; 4-Piperidinesulfonamide,1-ethyl-N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-; CHEMBL5095423; CS-0204138; Example 6 [WO2019008025A1]; GTPL12173; HY-132831; MFCD34579587; MS-26540; RG6418; RG-6418; RO7486967; RO-7486967; SCHEMBL20634304; Selnoflast; Selnoflast [INN]; Selnoflast [USAN:INN]; Selnoflast [USAN]; SY347075; T23RPA8WA2; UNII-T23RPA8WA2; WHO 11687
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MOA Inhibitor
External Link
 Compound Name MCC950 Investigative [5]
Synonyms
210826-40-7; MCC-950; CP-456773; CHEMBL3183703; N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-4-(1-hydroxy-1-methylethyl)-2-furansulfonamide; MCC 950; DSSTox_RID_82252; DSSTox_CID_27301; DSSTox_GSID_47301; SCHEMBL6521858; GTPL8228; DTXSID2047301; MolPort-042-579-517; EX-A1052; BCP15729; Tox21_300462; BDBM50155926; ZINC34025113; AKOS030238802; SB19010; NCGC00254269-01; NCGC00248064-01; HY-12815; CAS-210826-40-7; 1-[4-(1-Hydroxy-1-methylethyl)-2-furylsulfonyl]-3-[(1,2,3,5,6,7-hexahydro-s-indacene)-4-yl]urea
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MOA Inhibitor
Activity IC50 = 5 nM
External Link
References
Ref 1 Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage. Stem Cell Res Ther. 2022 Jul 16;13(1):322. doi: 10.1186/s13287-022-03005-9.
Ref 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 3 National Cancer Institute Drug Dictionary (drug name BMS-986299).
Ref 4 Clinical pipeline report, company report or official report of Roche
Ref 5 A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55.