m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03005
 [1]
Histone modification H3K9me3 KDM4A ALKBH5 Direct Enhancement m6A modification DNMT3B DNMT3B ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 4A (KDM4A) ERASER View Details
Regulated Target Histone H3 lysine 9 trimethylation (H3K9me3) View Details
Downstream Gene ALKBH5 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 Expression of ALKBH5 is enhanced during IVD degeneration and NPC senescence, due to decreased KDM4A-mediated Histone H3 lysine 9 trimethylation (H3K9me3) modification. Functionally, ALKBH5 causes NPC senescence by demethylating DNA (cytosine-5)-methyltransferase 3B (DNMT3B) transcripts and in turn promoting its expression via less YTHDF2 recognition and following degradation due to transcript hypomethylation in vitro and in vivo. Increased DNMT3B promotes the development of IVD degeneration and NPC senescence, mechanistically by methylating CpG islands of E4F1 at the promoter region and thus restraining its transcription and expression.
Responsed Disease Intervertebral disc degeneration ICD-11: FA80
 Disease Info 
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DNA (cytosine-5)-methyltransferase 3B (DNMT3B) 22 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Curcumin Phase 3 [2]
Synonyms
458-37-7; Diferuloylmethane; Natural yellow 3; Turmeric yellow; Turmeric; Curcuma; Kacha haldi; Gelbwurz; Indian saffron; Curcumin I; Souchet; Halud; Halad; Haidr; Haldar; Merita earth; Yellow Ginger; Terra Merita; Yellow Root; Safran d'Inde; Yo-Kin; Golden seal; Curcuma oil; Orange Root; Oils, curcuma; CI Natural Yellow 3; Curcumine; Hydrastis; Indian turmeric; Yellow puccoon; Turmeric extract; Diferaloylmethane; Kurkumin [Czech]; (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; Tumeric yellow; Turmeric oil
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MOA Inhibitor
External Link
CID: 969516
TTD: D07SDQ
DrugBank: DB11672
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
 Compound Name NSC-622444 Investigative [2]
Synonyms
NSC622444; CHEMBL116347; AC1Q3LXD; AC1L7GK5; SCHEMBL9755151; dichlorinated diacylmethane fragment; ZINC1616868; BDBM50048522; 5,3'-dicarboxy-4,4'-dihydrodiphenylmethane; 5,5''-methylenebis(3-chloro-2-hydroxybenzoic acid); 5,5'-Methylenebis(3-chloro-2-hydroxybenzoic acid); 3,3'-methanediylbis(5-chloro-6-hydroxybenzoic acid); 5-(3-carboxy-5-chloro-4-hydroxybenzyl)-3-chloro-2-hydroxybenzoic acid; 3',3-Dichloro-4',4-dimethoxy-5',5-bis(methoxycarbonyl)-1,1-diphenylmethane
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MOA Inhibitor
External Link
CID: 360384
TTD: D01VNN
 Compound Name NSC-138419 Investigative [2]
Synonyms
NSC138419; n-[4-(methylamino)benzoyl]glutamic acid; AC1Q5SG8; AC1L5YW4; SCHEMBL5925511; CHEMBL591443; CTK1H0013; 2-[(4-methylaminobenzoyl)amino]pentanedioic acid; A816490; 2-[[4-(methylamino)benzoyl]amino]pentanedioic acid; 2-[[4-(methylamino)phenyl]carbonylamino]pentanedioic acid; 2-[[[4-(methylamino)phenyl]-oxomethyl]amino]pentanedioic acid
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MOA Inhibitor
External Link
CID: 283555
TTD: D03PWU
 Compound Name NSC-319745 Investigative [2]
Synonyms
61629-60-5; HB 093; BRN 2168571; 4-(2-((5-Chloro-2-methoxybenzoyl)amino)ethyl)hydrocinnamic acid; 3-[4-[2-[(5-CHLORO-2-METHOXY-BENZOYL)AMINO]ETHYL]PHENYL]PROPANOIC ACID; 3-(4-(2-(5-Chlor-2-methoxy-benzamido)-aethyl)phenyl)-propionsaeure [German]; 3-[4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]phenyl]propanoic acid; HYDROCINNAMIC ACID, 4-(2-((5-CHLORO-2-METHOXYBENZOYL)AMINO)ETHYL)-; AC1L2AFL; CHEMBL597112; SCHEMBL11481071; CTK5B3505; DTXSID00210642; AIEFQKOARQRACO-UHFFFAOYSA-N; ZINC1572211; HB-093; NSC319745
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MOA Inhibitor
External Link
CID: 43709
TTD: D06RGX
 Compound Name NSC-348926 Investigative [2]
Synonyms
NSC348926; 2-phthalimidoadipic acid; AC1L7IP1; SCHEMBL9741723; CHEMBL599367; 2-(1,3-dioxoisoindol-2-yl)hexanedioic acid
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MOA Inhibitor
External Link
CID: 336008
TTD: D06VVV
 Compound Name NSC-401077 Investigative [2]
Synonyms
NSC401077; MLS000757170; DNA Methyltransferase Inhibitor; CHEMBL383475; 32675-71-1; 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(1H-indol-3-yl)-propionic acid; 2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propanoic acid; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propionic acid; SMR000413613; AC1Q71QA; Oprea1_475901; Oprea1_410805; MLS000777218; MLS006011919; SCHEMBL562060
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MOA Inhibitor
External Link
CID: 344265
TTD: D07VWC
 Compound Name S-tubercidinylhomocysteine Investigative [4]
Synonyms
CHEMBL552309; 57344-98-6; AC1L3YAS; AC1Q5QMO; (S)-7-(5-S-(3-amino-3-carboxypropyl)-5-thio-beta-D-ribofuranosyl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine; (2s)-2-amino-4-({[(2s,3s,4r,5r)-5-(4-amino-7h-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)butanoic acid(non-preferred name); BDBM50294482; (2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid
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MOA Inhibitor
Activity IC50 = 300 nM
External Link
CID: 124349
TTD: D08TGQ
 Compound Name NSC-106084 Investigative [2]
Synonyms
CHEMBL597113; NSC106084; AC1L6H8Q; CTK7J5419; ZINC1868549; BDBM50308983; {4-[5-bromo-2-(carboxymethoxy)benzoyl]phenoxy}acetic acid; 2-(4-bromo-2-(4-(carboxymethoxy)benzoyl)phenoxy)acetic acid; 2-[4-[5-bromo-2-(carboxymethyloxy)benzoyl]phenoxy]acetic acid
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MOA Inhibitor
External Link
CID: 266989
TTD: D0A2ZH
 Compound Name NSC-154957 Investigative [2]
Synonyms
NSC154957; AC1L6EF2; CHEMBL586418; 3-benzhydrylsulfanyl-2-formamidopropanoic acid
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MOA Inhibitor
External Link
CID: 290753
TTD: D0C4NA
 Compound Name NSC-54162 Investigative [2]
Synonyms
NSC54162; AC1Q5WTA; AC1L6CM2; CHEMBL611994; 2,2'-{[(2-hydroxyphenyl)methanediyl]disulfanediyl}diacetic acid; ZINC1685025; Acetic acid, (salicylidenedithio)di-; 4265-51-4; Acetic acid, [(o-hydroxybenzylidene)dithio]di-; Acetic acid,2'-[[(2-hydroxyphenyl)methylene]bis(thio)]bis-; 2-[carboxymethylsulfanyl-(2-hydroxyphenyl)methyl]sulfanylacetic acid
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MOA Inhibitor
External Link
CID: 243918
TTD: D0FN7C
 Compound Name NSC-57893 Investigative [2]
Synonyms
MLS002667915; 7399-94-2; 4-[(1h-benzimidazol-2-ylmethyl)(formyl)amino]benzoic acid; NSC57893; AC1L6GFK; AC1Q5TWY; NCIOpen2_002368; CHEMBL599366; 4-[1H-benzimidazol-2-ylmethyl(formyl)amino]benzoic acid; CTK5D9099; DTXSID30288854; HMS3089M13; ZINC1688755; AKOS030547711
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MOA Inhibitor
External Link
CID: 245689
TTD: D0G9NS
 Compound Name NSC-56071 Investigative [2]
Synonyms
32230-52-7; NSC56071; AC1L6EJV; AC1Q7ES0; NCIOpen2_007380; CHEMBL596910; CTK4G8394; DTXSID80288485; ZINC1686711; 2,2'-[piperazine-1,4-diylbis(carbonothioylsulfanediyl)]diacetic acid; AKOS030574801; Acetic acid,2,2'-[1,4-piperazinediylbis(carbonothioylthio)]bis- (9CI); 2-[4-(carboxymethylsulfanylcarbothioyl)piperazine-1-carbothioyl]sulfanylacetic acid
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MOA Inhibitor
External Link
CID: 244824
TTD: D0H1YK
 Compound Name NSC-137546 Investigative [2]
Synonyms
NSC137546; CHEMBL591202; AC1L5Y49; AKOS008984447; 2-[(2,6-dichlorobenzoyl)amino]pentanedioic acid
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MOA Inhibitor
External Link
CID: 283188
TTD: D0I5JP
 Compound Name NSC-623548 Investigative [2]
Synonyms
2581-36-4; NSC 408488; o-Cresotic acid, 5,5'-methylenedi-; 2,3-CRESOTIC ACID, 5,5'-METHYLENEDI-; UNII-S3D8KC88KC; 5,5'-Methylenedi-2,3-cresotic acid; NSC 623548; BRN 3433298; S3D8KC88KC; CHEMBL113835; 5,5'-Methylenedi-o-cresotic acid; NSC623548; NSC408488; 5,5'-Methylenebis(2-hydroxy-3-methylbenzoic acid); 2, 5,5'-methylenedi-; AC1L29YK; Oprea1_231968; 2-10-00-00398 (Beilstein Handbook Reference); SCHEMBL9755153; CTK4F6504; DTXSID90180466; o-Cresotic acid,5'-methylenedi-; MolPort-000-698-522; ZINC4028795; STL511095
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MOA Inhibitor
External Link
CID: 17413
TTD: D0LS2U
 Compound Name NSC-345763 Investigative [2]
Synonyms
7-(8-hydroxyquinolin-5-yl)-4,7-dioxoheptanoic acid; NSC345763; AC1L7HSU; CHEMBL597114
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MOA Inhibitor
External Link
CID: 335596
TTD: D0MP7N
 Compound Name NSC-158324 Investigative [2]
Synonyms
Acediasulfone; UNII-30YP2YHH8W; 30YP2YHH8W; CHEMBL48396; N-[4-[(4-AMINOPHENYL)SULPHONYL]PHENYL]GLYCINE; 2-[4-(4-aminophenyl)sulfonylanilino]acetic acid; Acediasulfonum; N-(4-((4-Aminophenyl)sulphonyl)phenyl)glycine; EINECS 201-243-7; AC1L25EF; ZINC862; SCHEMBL143660; CTK5E7379; DTXSID00229991; CHEBI:135300; BDBM50099670; AKOS027327086; DB08926; Glycine,N-[4-[(4-aminophenyl)sulfonyl]phenyl]-; {4-[(4-aminophenyl)sulfonyl]anilino}acetic acid; 2-(4-(4-aminophenylsulfonyl)phenylamino)acetic acid
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MOA Inhibitor
External Link
CID: 24193827
TTD: D0W5SZ
 Compound Name (L-)-S-adenosyl-L-homocysteine Investigative [5]
Synonyms
S-Adenosyl-L-homocysteine; S-adenosylhomocysteine; 979-92-0; AdoHcy; S-(5'-adenosyl)-L-homocysteine; adenosylhomocysteine; Formycinylhomocysteine; Adenosyl-L-homocysteine; S-(5'-deoxyadenosin-5'-yl)-L-homocysteine; 2-S-adenosyl-L-homocysteine; 5'-Deoxy-S-adenosyl-L-homocysteine; S-adenosyl-homocysteine; S-Adenosyl Homocysteine; L-S-Adenosylhomocysteine; L-Homocysteine, S-(5'-deoxyadenosin-5'-yl)-; adenosylhomo-cys; adenosyl-homo-cys; UNII-8K31Q2S66S; (S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine; BRN 5166233; SAH
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MOA Inhibitor
Activity IC50 = 200 nM
External Link
CID: 439155
TTD: D09CLP
DrugBank: DB01752
 Compound Name NSC-622445 Investigative [2]
Synonyms
5,5'-Methylenedisalicylic acid; 122-25-8; 5,5'-Methylenebis(2-hydroxybenzoic acid); Methylenebis(salicylic acid); 5,5-Methylenebis(salicylic acid); UNII-2KF4FVV76N; 5,5-Methylenedisalicylic acid; 5-(3-Carboxy-4-hydroxybenzyl)salicylic acid; 4,4'-Dihydroxy-3,3'-dicarboxydiphenylmethane; 3,3'-Dicarboxy-4,4'-dihydroxydiphenylmethane; NSC 14778; 2KF4FVV76N; 4,4'-Dihydroxydiphenylmethane-3,3'-dicarboxylic acid; 3,3'-Methylenebis(6-hydroxybenzoic acid); CHEMBL115145; Benzoic acid, 3,3'-methylenebis[6-hydroxy-
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MOA Inhibitor
Activity IC50 = 17000 nM
External Link
CID: 67145
TTD: D0J5VK
Lysine-specific demethylase 4A (KDM4A) 11 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Disulfiram analog 1 Patented [6]
Synonyms
PMID25468267-Compound-26
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MOA Inhibitor
Activity IC50 = 15300 nM
External Link
CID: 6451399
TTD: D05PXW
 Compound Name Selenium compound 2 Patented [6]
Synonyms
PMID25468267-Compound-29
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MOA Inhibitor
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CID: 21928
TTD: D09YFD
 Compound Name Disulfiram analog 2 Patented [6]
Synonyms
PMID25468267-Compound-27
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MOA Inhibitor
Activity IC50 = 3300 nM
External Link
CID: 575125
TTD: D0JQ9Z
 Compound Name Selenium compound 1 Patented [6]
Synonyms
PMID25468267-Compound-28
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MOA Inhibitor
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CID: 23427
TTD: D0X2AU
 Compound Name Selenium compound 3 Patented [6]
Synonyms
PMID25468267-Compound-30
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MOA Inhibitor
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CID: 3194
TTD: D0X6SJ
DrugBank: DB12610
 Compound Name Heteroaryl-cyclopropylamine derivative 4 Patented [7]
Synonyms
PMID27019002-Compound-22c
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MOA Inhibitor
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TTD: D01CIK
 Compound Name PMID27019002-Compound-21b Patented [7]
MOA Inhibitor
External Link
TTD: D07MQD
 Compound Name Hydroxamate analog 1 Patented [6]
Synonyms
PMID25468267-Compound-31
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MOA Inhibitor
Activity IC50 = 3000 nM
External Link
TTD: D0MJ4L
 Compound Name PMID27019002-Compound-21c Patented [7]
MOA Inhibitor
External Link
TTD: D0UE4K
 Compound Name PMID25468267-Compound-46 Patented [6]
MOA Inhibitor
Activity IC50 = 4300 nM
External Link
CID: 53392492
TTD: D09NCT
 Compound Name N-(2-phenylcyclopropyl) amino acid derivative 1 Patented [7]
Synonyms
PMID27019002-Compound-19
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MOA Inhibitor
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TTD: D0UL9U
FA80: Intervertebral disc degeneration 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Rexlemestrocel-L Phase 3 [8]
Synonyms
MPC-150-M
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External Link
TTD: DHV2L8
 Compound Name CybroCell Phase 1/2 [9]
External Link
TTD: DS6C1Y
 Compound Name IDCT Phase 1/2 [10]
Synonyms
rebonuputemcel
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External Link
TTD: DK65RJ
References
Ref 1 m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clin Transl Med. 2022 Mar;12(3):e765. doi: 10.1002/ctm2.765.
Ref 2 Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9. doi: 10.1016/j.bmc.2009.11.050. Epub 2009 Nov 27.
Ref 3 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 4 SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes. Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28.
Ref 5 Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
Ref 6 KDM4 histone demethylase inhibitors for anti-cancer agents: a patent review.Expert Opin Ther Pat. 2015 Feb;25(2):135-44.
Ref 7 LSD1 inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2016 May;26(5):565-80.
Ref 8 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 9 Clinical pipeline report, company report or official report of FibroGenesis.
Ref 10 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.