m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05607
 [1]
m6A modification hsa-miR-34a hsa-miR-34a METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-34a SIRT1  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target hsa-miR-34a
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-34a microRNA View Details
Regulated Target NAD-dependent protein deacetylase sirtuin-1 (SIRT1) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary METTL3/m6A-mediated hsa-miR-34a maturation in AAA formation and provide a novel therapeutic target and diagnostic biomarker for AAA treatment. miR-34a overexpression significantly decreased NAD-dependent protein deacetylase sirtuin-1 (SIRT1) expression.
Responsed Disease Abdominal aortic aneurysm ICD-11: BD50.4
 Disease Info 
In-vitro Model
 VSMC (Human aortic vascular smooth muscle cells)
In-vivo Model Male C57BL/6J mice were anesthetized with an intraperitoneal injection of pentobarbital (40 mg/kg). The abdominal aorta between the renal arteries and the bifurcation of the iliac arteries was disassociated from the surrounding structures. Video microscopy was used to assay the diameter of the aorta in triplicate. After the measurements were taken, a small piece of gauze dipped in 0.5 mol/L CaCl2 was spread perivascularly onto the aortic passage for 15 min. Control mice received substitute treatment with NaCl (0.9%)-soaked gauze for 15 min. Then, the aorta was rinsed with 0.9% sterile saline, and the incision was sutured. After 3 or 6 weeks, all the animals were sacrificed, and the aortas were harvested for further analysis.
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 [2]
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
    Click to Show/Hide
MOA Inhibitor
Activity EC50 = 23600 nM
External Link
CID: 445154
TTD: D0U3EP
DrugBank: DB02709
 Compound Name GSK2245840 Phase 2 [3]
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,
    Click to Show/Hide
MOA Modulator
External Link
CID: 25108829
TTD: D04JNI
DrugBank: DB12186
 Compound Name SEN-196 Phase 2 [4]
Synonyms
EX-527; SEN-0014196; SIRT1 inhibitors (Huntingtons disease), Elixir/Siena; Sirtuin-1 inhibitors (oral, Huntington's disease), Elixir/Siena
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 85 nM
External Link
CID: 5113032
TTD: D0E3LP
DrugBank: DB13978
 Compound Name MB-12066 Phase 2 [5]
Synonyms
B-lapachone (obesity), Mazence; Beta-lapachone (obesity), Mazence
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MOA Modulator
External Link
TTD: D0TU7V
 Compound Name SRT2379 Phase 1 [6]
MOA Modulator
External Link
TTD: D0O3EP
 Compound Name SRT3025 Phase 1 [7]
MOA Modulator
External Link
CID: 46245047
TTD: D0X3TI
 Compound Name PMID25435179-Compound-WO2012106509Salermide Patented [2]
MOA Inhibitor
External Link
TTD: D02QKC
 Compound Name CAMBINOL Patented [8]
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 [2]
MOA Inhibitor
External Link
TTD: D06IHB
 Compound Name PMID25435179-Compound-WO2012106509Tenovin-6 Patented [2]
MOA Inhibitor
External Link
TTD: D0PE8E
 Compound Name GSK184072 Discontinued in Phase 2 [9]
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 [10]
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 [11]
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)
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 5300 nM
External Link
CID: 1403654
TTD: D02AYX
 Compound Name (R)-sirtinol Investigative [10]
MOA Inhibitor
Activity IC50 = 55000 nM
External Link
CID: 1376646
TTD: D02EWM
 Compound Name SRT1720 Investigative [12]
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 [13]
Synonyms
Angiogenesis inhibitors (cancer); Angiogenesis inhibitors (cancer), Georgetown University
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MOA Inhibitor
External Link
TTD: D05UDU
 Compound Name splitomicin Investigative [11]
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 [14]
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-
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1470 nM
External Link
CID: 4262314
TTD: D0E1QP
 Compound Name (S)-sirtinol Investigative [10]
MOA Inhibitor
Activity IC50 = 67000 nM
External Link
CID: 1376645
TTD: D0F1KR
 Compound Name Para-sirtinol Investigative [10]
MOA Inhibitor
Activity IC50 = 13000 nM
External Link
CID: 135491748
TTD: D0UO1E
 Compound Name Ro31-8220 Investigative [15]
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 [15]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 2399
TTD: D0L8HO
BD50: Aortic aneurysm or dissection 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name CRD-007 Phase 2 [16]
External Link
TTD: D06JNC
 Compound Name WAY-644 Investigative [17]
Synonyms
MMP-12 inhibitor (aortic abdominal aneurysm), Pfizer; MMP-12 inhibitor (aortic abdominal aneurysm), Wyeth
    Click to Show/Hide
External Link
TTD: D07NDK
 Compound Name VDA-1124 Investigative [18]
Synonyms
Granzyme B inhibitors (abdominal aortic aneurysms), viDA Therapeutics
    Click to Show/Hide
External Link
TTD: D06UZS
References
Ref 1 METTL3 Induces AAA Development and Progression by Modulating N6-Methyladenosine-Dependent Primary miR34a Processing. Mol Ther Nucleic Acids. 2020 Sep 4;21:394-411. doi: 10.1016/j.omtn.2020.06.005. Epub 2020 Jun 10.
Ref 2 Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
Ref 3 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 4 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69. doi: 10.1177/1087057111422103. Epub 2011 Nov 15.
Ref 5 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 6 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
Ref 7 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 8 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 9 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
Ref 10 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 11 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 12 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 13 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 14 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 15 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.
Ref 16 ClinicalTrials.gov (NCT01540604) CRD007 for the Treatment of Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and Symptomatic Carriers. U.S. National Institutes of Health.
Ref 17 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: 1636).
Ref 18 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: 2369).