m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03142
 [1]
Histone modification H3K36me1 SMYD2 METTL3 Direct Enhancement m6A modification m6A Target m6A Target METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator N-lysine methyltransferase SMYD2 (SMYD2) WRITER View Details
Regulated Target Histone H3 lysine 36 monomethylation (H3K36me1) 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 Histone H3 lysine 36 monomethylation (H3K36me1) plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.
Responsed Disease Structural developmental anomalies of large intestine ICD-11: LB16.1
 Disease Info 
Cell Process Cell proliferation
Cell migration
In-vitro Model
 SH-SY5Y Neuroblastoma Homo sapiens CVCL_0019
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
N-lysine methyltransferase SMYD2 (SMYD2) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name AZ505 Preclinical [2]
Synonyms
AZ 505; AZ-505
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MOA Inhibitor
Activity IC50 = 120 nM
External Link
CID: 24961094
TTD: D06ONB
 Compound Name LLY-507 Preclinical [3]
Synonyms
1793053-37-8; LLY507; CHEMBL3414623; 5-Cyano-2'-{4-[2-(3-Methyl-1h-Indol-1-Yl)ethyl]piperazin-1-Yl}-N-[3-(Pyrrolidin-1-Yl)propyl]biphenyl-3-Carboxamide; 3-cyano-5-(2-{4-[2-(3-methyl-1H-indol-1-yl)ethyl]piperazin-1-yl}phenyl)-N-[3-(pyrrolidin-1-yl)propyl]benzamide; 3-Cyano-5-[2-[4-[2-(3-methyl-1H-indol-1-yl)ethyl]piperazin-1-yl]phenyl]-N-[3-(pyrrolidin-1-yl)propyl]benzamide; GTPL8239; SCHEMBL19760400; EX-A899; LLY 507; MolPort-042-624-530; BCP17114; s7575; BDBM50075102; ZINC231558920; AKOS027470175; CS-5126
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MOA Inhibitor
Activity IC50 < 15 nM
External Link
CID: 91623361
TTD: D0X3RK
 Compound Name EPZ032597 Preclinical [4]
MOA Inhibitor
External Link
TTD: D35SKV
 Compound Name EPZ033294 Preclinical [4]
MOA Inhibitor
External Link
TTD: DDC63W
 Compound Name A-893 Preclinical [5]
Synonyms
1868232-32-9; (R)-N-cyclohexyl-3-((3,4-dichlorophenethyl)amino)-N-(2-((2-hydroxy-2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)amino)ethyl)propanamide; CHEMBL3590526; N-Cyclohexyl-N~3~-[2-(3,4-Dichlorophenyl)ethyl]-N-(2-{[(2r)-2-Hydroxy-2-(3-Oxo-3,4-Dihydro-2h-1,4-Benzoxazin-8-Yl)ethyl]amino}ethyl)-Beta-Alaninamide; SCHEMBL17476248; EX-A2769; BDBM50095537; AKOS030235552; ZINC230499113; ACN-037539; AC-29886; HY-19563; CS-0015655; Q27454706; 4GQ; N-Cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2R)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide
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MOA Inhibitor
External Link
CID: 91757965
TTD: DELC48
 Compound Name BAY 598 Preclinical [6]
Synonyms
BAY-598; 1906919-67-2; CHEMBL3818617; 1906919-67-2 (S-isomer); (S,E)-N-(1-(N'-cyano-N-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; BAY 598 - Bio-X; BAY598; GTPL8953; EX-A1835; BDBM50180955; ZINC504786915; AC-31567; BS-16389; HY-19546; CS-0015642; J3.601.000B; Q27074893; (S)-N-(1-(N'-Cyano-N-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; (S,E)-N-(1-(N-cyano-N'-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; (S,Z)-N-(1-(N-cyano-N'-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; N-[(4S)-1-[(Cyanoamino)[[3-(difluoromethoxy)phenyl]imino]methyl]-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide; N-[(4S)-1-[(Z)-N'-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl]-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide
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MOA Inhibitor
External Link
CID: 117072551
TTD: DT6P8M
References
Ref 1 H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3. J Cell Physiol. 2024 Sep;239(9):e31402. doi: 10.1002/jcp.31402. Epub 2024 Aug 7.
Ref 2 Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73.
Ref 3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2714).
Ref 4 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 5 Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. ACS Med Chem Lett. 2015 Apr 29;6(6):695-700.
Ref 6 Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2. J Med Chem. 2016 May 26;59(10):4578-600.