m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00676
 [1], [2], [3]
m6A modification hsa-mir-19b-1 hsa-mir-19b-1 METTL3 Methylation : m6A sites Indirect Enhancement RNA modification SIRT1 SIRT1 FTO Demethylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target hsa-mir-19b-1
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N6,2'-O-dimethyladenosine (m6Am)
Epigenetic Regulator Fat mass and obesity-associated protein (FTO) ERASER View Details
Regulated Target NAD-dependent protein deacetylase sirtuin-1 (SIRT1) View Details
Crosstalk Relationship m6A  →  m6Am Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary METTL3 interacts with hsa-mir-19b-1, decreasing its m6A level and promoting its physical interaction with NAD-dependent protein deacetylase sirtuin-1 (SIRT1), which was regulated by FTO-mediated m6Am modification.
In-vitro Model
 Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) 22 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Resveratrol Phase 3 [4]
Synonyms
Resvida; KUC104385N; R 5010; SRT 501; Cis-resveratrol; PREVENTION 8 (RESVERATROL); RM-1812; SRT-501; Trans-resveratrol; CU-01000001503-3; KSC-10-164; Resveratrol-3-sulfate; Trans-3,4',5-trihydroxystilbene; Trans-3,4′,5-Trihydroxystilbene; Trans-1,2-(3,4',5-Trihydroxydiphenyl)ethylene; (E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol
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MOA Inhibitor
Activity EC50 = 23600 nM
External Link
CID: 445154
TTD: D0U3EP
DrugBank: DB02709
 Compound Name GSK2245840 Phase 2 [5]
Synonyms
Gepirone hydrochloride; Gepirone HCl; UNII-80C9L8EP6V; Gepirone hydrochloride [USAN]; 80C9L8EP6V; 83928-66-9; CHEMBL1204187; Gepirone hydrochloride (USAN); BMY 138951; AC1Q3ELB; AC1L1IK3; SCHEMBL318838; DTXSID30232812; AOB5299; 83928-76-1 (Parent); ORG-33062; SB19633; BMY-13805-1; BMY 13805-1; 3,3-Dimethyl-1-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)glutarimide monohydrochloride; D04314; 4,4-dimethyl-1-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione hydrochloride; 2,6-Piperidinedione,
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MOA Modulator
External Link
CID: 25108829
TTD: D04JNI
DrugBank: DB12186
 Compound Name SEN-196 Phase 2 [6]
Synonyms
EX-527; SEN-0014196; SIRT1 inhibitors (Huntingtons disease), Elixir/Siena; Sirtuin-1 inhibitors (oral, Huntington's disease), Elixir/Siena
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MOA Inhibitor
Activity IC50 = 85 nM
External Link
CID: 5113032
TTD: D0E3LP
DrugBank: DB13978
 Compound Name MB-12066 Phase 2 [7]
Synonyms
B-lapachone (obesity), Mazence; Beta-lapachone (obesity), Mazence
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MOA Modulator
External Link
TTD: D0TU7V
 Compound Name SRT2379 Phase 1 [8]
MOA Modulator
External Link
TTD: D0O3EP
 Compound Name SRT3025 Phase 1 [9]
MOA Modulator
External Link
CID: 46245047
TTD: D0X3TI
 Compound Name PMID25435179-Compound-WO2012106509Salermide Patented [4]
MOA Inhibitor
External Link
TTD: D02QKC
 Compound Name CAMBINOL Patented [10]
Synonyms
14513-15-6; SIRT1/2 Inhibitor IV, Cambinol; NSC112546; NSC-112546; NSC-1125476; 5-[(2-hydroxy-1-naphthyl)methyl]-2-mercapto-6-phenyl-4(3H)-Pyrimidinone; 5-(2-Hydroxynaphthalen-1-ylmethyl)-6-phenyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one; 5-(2-Hydroxy-naphthalen-1-ylmethyl)-6-phenyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one; Tetrahydro-5-[(2-hydroxy-1-naphthalenyl)methyl]-6-phenyl-2-thioxo-4(1H)-Pyrimidinone; AC1MMYEF; NCIStruc2_001159; NCIStruc1_001428; SCHEMBL2538372; CHEMBL491960; CTK8G3107; BDBM29040
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MOA Inhibitor
Activity IC50 = 8850 nM
External Link
CID: 3246390
TTD: D04JZE
DrugBank: DB15493
 Compound Name PMID25435179-Compound-WO2012106509CAY10602 Patented [4]
MOA Inhibitor
External Link
TTD: D06IHB
 Compound Name PMID25435179-Compound-WO2012106509Tenovin-6 Patented [4]
MOA Inhibitor
External Link
TTD: D0PE8E
 Compound Name GSK184072 Discontinued in Phase 2 [11]
Synonyms
Flutimide; 162666-34-4; AC1O5YLM; AKOS027326745; (5Z)-1-hydroxy-3-isobutyl-5-(2-methylpropylidene)pyrazine-2,6-dione; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (Z)-; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (3Z)-; (5Z)-1-hydroxy-3-(2-methylpropyl)-5-(2-methylpropylidene)pyrazine-2,6-dione
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MOA Activator
External Link
CID: 6443207
TTD: D0R3EL
 Compound Name Meta-sirtinol Investigative [12]
MOA Inhibitor
Activity IC50 = 59000 nM
External Link
CID: 135461039
TTD: D00LYI
 Compound Name 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dione Investigative [13]
Synonyms
CHEMBL611665; chromeno[2,3-d]pyrimidine-2,4-dione; AC1LQMEG; 5-Deaza-10-oxaflavin; SCHEMBL11333239; BFMCRAXOACCPEL-UHFFFAOYSA-; ZINC1280587; STK236511; BDBM50309832; AKOS000428551; MCULE-3496773034; ST50987740; 3-hydrochromeno[2,3-d]pyrimidine-2,4-dione; 2H,3H,4H-chromeno[2,3-d]pyrimidine-2,4-dione; 2H-[1]Benzopyrano[2,3-d]pyrimidine-2,4(3H)-dione; InChI=1/C11H6N2O3/c14-9-7-5-6-3-1-2-4-8(6)16-10(7)13-11(15)12-9/h1-5H,(H,12,14,15)
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MOA Inhibitor
Activity IC50 = 5300 nM
External Link
CID: 1403654
TTD: D02AYX
 Compound Name (R)-sirtinol Investigative [12]
MOA Inhibitor
Activity IC50 = 55000 nM
External Link
CID: 1376646
TTD: D02EWM
 Compound Name SRT1720 Investigative [14]
Synonyms
925434-55-5; N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide; SRT 1720; SRT-1720; CHEMBL257991; N-[2-[3-(1-PIPERAZINYLMETHYL)IMIDAZO[2,1-B]THIAZOL-6-YL]PHENYL]-2-QUINOXALINECARBOXAMIDE; N-(2-{3-[(Piperazin-1-yl)methyl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)quinoxaline-2-carboxamide; Tafluprost enone; N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide; IASPBORHOMBZMY-UHFFFAOYSA-N
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MOA Activator
External Link
CID: 25232708
TTD: D03EGA
 Compound Name YK-3237 Investigative [15]
Synonyms
Angiogenesis inhibitors (cancer); Angiogenesis inhibitors (cancer), Georgetown University
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MOA Inhibitor
External Link
TTD: D05UDU
 Compound Name splitomicin Investigative [13]
Synonyms
1,2-Dihydro-3H-naphtho[2,1-b]pyran-3-one; 1,2-dihydro-3h-benzo[f]chromen-3-one; 1H-benzo[f]chromen-3(2H)-one; CHEMBL86537; CHEBI:75272; 1,2-dihydrobenzo[f]chromen-3-one; 1H,2H,3H-naphtho[2,1-b]pyran-3-one; Splitomycin; Bio2_000878; Tocris-1542; AC1L1JZ6; AC1Q6ML4; KBioGR_000456; BSPBio_001116; KBioSS_000456; GTPL8101; SCHEMBL2544804; ZINC27374; KBio3_000852; KBio2_003024; BDBM29590; KBio3_000851; KBio2_005592; KBio2_000456; MolPort-003-959-546; ISFPDBUKMJDAJH-UHFFFAOYSA-N; HMS1362H17; HMS1990H17; Bio2_000398
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MOA Inhibitor
Activity IC50 = 96200 nM
External Link
CID: 5269
TTD: D09SUO
 Compound Name 2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide Investigative [16]
Synonyms
CHEMBL112265; 352549-39-4; CBMicro_001045; Cambridge id 5870454; AC1N6ME3; Oprea1_743470; SCHEMBL251128; CTK1B0687; DTXSID20401358; MolPort-000-735-346; HMS1632P07; SMSF0008851; STL525366; BDBM50178767; carboxamido-1,2,3-tetrahydrocarbazole; AKOS004917884; CB02357; BIM-0000968.P001; SR-01000154363; SR-01000154363-1; 1H-Carbazole-1-carboxamide, 2,3,4,9-tetrahydro-
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MOA Inhibitor
Activity IC50 = 1470 nM
External Link
CID: 4262314
TTD: D0E1QP
 Compound Name (S)-sirtinol Investigative [12]
MOA Inhibitor
Activity IC50 = 67000 nM
External Link
CID: 1376645
TTD: D0F1KR
 Compound Name Para-sirtinol Investigative [12]
MOA Inhibitor
Activity IC50 = 13000 nM
External Link
CID: 135491748
TTD: D0UO1E
 Compound Name Ro31-8220 Investigative [17]
Synonyms
Bisindolylmaleimide IX; ro 31-8220; 125314-64-9; Ro 31 8220; Ro 318220; UNII-W9A0B5E78O; Ro-318220; Ro-31-8220; CHEMBL6291; W9A0B5E78O; CHEBI:38912; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl imidothiocarbamate; CHEMBL1591531; Carbamimidothioic acid, 3-(3-(2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl; bisindolymaleimide IX
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MOA Inhibitor
Activity IC50 = 3500 nM
External Link
CID: 5083
TTD: D0M5FF
 Compound Name RO-316233 Investigative [17]
Synonyms
119139-23-0; bisindolylmaleimide iv; 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-dione; Arcyriarubin A; 3,4-Bis(3-indolyl)maleimide; 3,4-Di-1H-indol-3-yl-1H-pyrrole-2,5-dione; UNII-MBK3OO5K8T; BIM IV; 3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione; MBK3OO5K8T; CHEMBL266487; 3,4-bis(1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione; DQYBRTASHMYDJG-UHFFFAOYSA-N; 2,3-bis(1H-Indol-3-yl)maleimide; 1H-Pyrrole-2,5-dione, 3,4-di-1H-indol-3-yl-; Ro-31-6233; AK-15401; 3,4-bis(3-indolyl)-1H-pyrrole-2,5-dione; Bisindoylmaleimide; Bisindolyl deriv. 3
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MOA Inhibitor
External Link
CID: 2399
TTD: D0L8HO
References
Ref 1 SIRT1 Regulates N(6) -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation. Hepatology. 2020 Dec;72(6):2029-2050. doi: 10.1002/hep.31222. Epub 2020 Oct 22.
Ref 2 N(6)-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN/TMEM127 and promotes sensitivity to everolimus in gastric cancer. Cell Death Dis. 2020 Oct 9;11(10):836. doi: 10.1038/s41419-020-03049-w.
Ref 3 LncRNA H19 inhibits high glucose-induced inflammatory responses of human retinal epithelial cells by targeting miR-19b to increase SIRT1 expression. Kaohsiung J Med Sci. 2021 Feb;37(2):101-110. doi: 10.1002/kjm2.12302. Epub 2020 Oct 6.
Ref 4 Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
Ref 5 Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52. doi: 10.1002/acn3.135. Epub 2014 Oct 31.
Ref 6 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69. doi: 10.1177/1087057111422103. Epub 2011 Nov 15.
Ref 7 Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy. PLoS One. 2013 Jun 10;8(6):e64953. doi: 10.1371/journal.pone.0064953. Print 2013.
Ref 8 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
Ref 9 The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391. doi: 10.1371/journal.pone.0134391. eCollection 2015.
Ref 10 Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82. doi: 10.1021/jm8014298.
Ref 11 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
Ref 12 Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. J Med Chem. 2005 Dec 1;48(24):7789-95. doi: 10.1021/jm050100l.
Ref 13 Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. J Med Chem. 2010 Feb 11;53(3):1407-11. doi: 10.1021/jm9013345.
Ref 14 Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6. doi: 10.1038/nature06261.
Ref 15 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: 2707).
Ref 16 Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J Med Chem. 2005 Dec 15;48(25):8045-54. doi: 10.1021/jm050522v.
Ref 17 Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition. J Med Chem. 2006 Dec 14;49(25):7307-16. doi: 10.1021/jm060118b.