m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05330
 [1]
Non-coding RNA miR-26a-5p METTL14  lncRNA       miRNA   circRNA Indirect Inhibition m6A modification NLRP3 NLRP3 IGFBP2 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor-binding protein 2 (IGFBP2) READER
 Regulator Info 
m6A Target NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-26a-5p microRNA View Details
Regulated Target Methyltransferase-like protein 14 (METTL14) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary Methyltransferase-like protein 14 (METTL14) was highly present in NP cells from IVDD patients, which stabilize NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1beta (IL-1beta) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal hsa-miR-26a-5p.
Responsed Disease Intervertebral disc degeneration ICD-11: FA80
 Disease Info 
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
CID: 12714644
TTD: D0TH5H
 Compound Name BMS-986299 Phase 1 [3]
MOA Agonist
External Link
TTD: D75LNO
 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
CID: 137402358
TTD: D7KRB9
 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
CID: 9910393
TTD: D09FGL
FA80: Intervertebral disc degeneration 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Rexlemestrocel-L Phase 3 [6]
Synonyms
MPC-150-M
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External Link
TTD: DHV2L8
 Compound Name CybroCell Phase 1/2 [7]
External Link
TTD: DS6C1Y
 Compound Name IDCT Phase 1/2 [8]
Synonyms
rebonuputemcel
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External Link
TTD: DK65RJ
References
Ref 1 Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3. Mol Med. 2021 Aug 19;27(1):91. doi: 10.1186/s10020-021-00355-7.
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.
Ref 6 ClinicalTrials.gov (NCT02412735) Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Subjects With Chronic Low Back Pain (MSB-DR003). U.S. National Institutes of Health.
Ref 7 Clinical pipeline report, company report or official report of FibroGenesis.
Ref 8 ClinicalTrials.gov (NCT03955315) Study to Evaluate the Safety and Preliminary Efficacy of IDCT, a Treatment for Symptomatic Lumbar Disc Degeneration. U.S. National Institutes of Health.