m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05154
 [1], [2]
Non-coding RNA miR-193a-3p ALKBH5  lncRNA       miRNA   circRNA Direct Inhibition m6A modification SIRT1 SIRT1 ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target NAD-dependent protein deacetylase sirtuin-1 (SIRT1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-193a-3p microRNA View Details
Regulated Target RNA demethylase ALKBH5 (ALKBH5) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary Suxiao Jiuxin Pill alleviates myocardial ischemia/reperfusion-induced autophagy via miR-193a-3p/ALKBH5 pathway.there was an enriched m6A motif in the 3'-UTR of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) genome, and ALKBH5 overexpression promoted the stability of SIRT1 mRNA.
Responsed Disease Injury of heart ICD-11: NB31
 Disease Info 
Responsed Drug Suxiao Jiuxin Pill
 Drug Info 
In-vitro Model
 H9c2(2-1) Normal Rattus norvegicus CVCL_0286
In-vivo Model Male C57BL/6 mice (25-30 g) were obtained from Vital River Laboratory Animal Technology (Beijing, China) and were provided adaptive feeding for a week at the suitable temperature and humidity. All animals were housed in micro-isolator cages with free access to food and water according to the Guide for the Care and Use of Laboratory Animals. The myocardial I/R operation were followed by previous research (Song et al., 2015). The mice were randomly divided into myocardial I/R group (n = 10) and sham group (n = 10). Mice were anesthetized (50 mg/kg pentobarbital sodium, intraperitoneal injection) before assays. The supine of mice were fixed on the operating table connected with the standard lead II electrocardiogram. The left thorax was cut to expose the heart and the left anterior descending (LAD) coronary artery was ligated by 7/0 sterile suture. Myocardial ischemia was induced by LAD ligation for 30 min followed by 120 min of reperfusion. Sham group mice underwent the same surgical procedures without LAD coronary artery ligation. After assay, the surviving animals were transferred to institution's animal department for euthanizing mice.
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 [3]
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 [4]
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 [5]
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 [6]
Synonyms
B-lapachone (obesity), Mazence; Beta-lapachone (obesity), Mazence
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0TU7V
 Compound Name SRT2379 Phase 1 [7]
MOA Modulator
External Link
TTD: D0O3EP
 Compound Name SRT3025 Phase 1 [8]
MOA Modulator
External Link
CID: 46245047
TTD: D0X3TI
 Compound Name PMID25435179-Compound-WO2012106509Salermide Patented [3]
MOA Inhibitor
External Link
TTD: D02QKC
 Compound Name CAMBINOL Patented [9]
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
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 8850 nM
External Link
CID: 3246390
TTD: D04JZE
DrugBank: DB15493
 Compound Name PMID25435179-Compound-WO2012106509CAY10602 Patented [3]
MOA Inhibitor
External Link
TTD: D06IHB
 Compound Name PMID25435179-Compound-WO2012106509Tenovin-6 Patented [3]
MOA Inhibitor
External Link
TTD: D0PE8E
 Compound Name GSK184072 Discontinued in Phase 2 [10]
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 [11]
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 [12]
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 [11]
MOA Inhibitor
Activity IC50 = 55000 nM
External Link
CID: 1376646
TTD: D02EWM
 Compound Name SRT1720 Investigative [13]
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 [14]
Synonyms
Angiogenesis inhibitors (cancer); Angiogenesis inhibitors (cancer), Georgetown University
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D05UDU
 Compound Name splitomicin Investigative [12]
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 [15]
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 [11]
MOA Inhibitor
Activity IC50 = 67000 nM
External Link
CID: 1376645
TTD: D0F1KR
 Compound Name Para-sirtinol Investigative [11]
MOA Inhibitor
Activity IC50 = 13000 nM
External Link
CID: 135491748
TTD: D0UO1E
 Compound Name Ro31-8220 Investigative [16]
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 [16]
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
NB31: Injury of heart 6 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name MyoCell Phase 2/3 [17]
Synonyms
MyoCell (TN)
    Click to Show/Hide
External Link
TTD: D0O7CO
 Compound Name Diannexin Phase 2 [18]
External Link
TTD: D07FQL
 Compound Name CMX-2043 Phase 2 [19]
External Link
CID: 49802864
TTD: D01TBJ
DrugBank: DB12795
 Compound Name ED1 Investigative [20]
Synonyms
ethylenediamine scaffold, 10; BDBM31426; 3-{2'-[{[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}(2-{(4-cyanophenyl)[(1-methyl-1H-imidazol-5-yl)methyl]amino}ethyl)sulfamoyl]biphenyl-3-yl}propanoic acid
    Click to Show/Hide
External Link
CID: 25181318
TTD: D0G1SN
 Compound Name ED45 Investigative [20]
External Link
TTD: D01NJE
 Compound Name DD7 Investigative [20]
External Link
TTD: D00QBV
References
Ref 1 Suxiao Jiuxin Pill alleviates myocardial ischemia/reperfusion-induced autophagy via miR-193a-3p/ALKBH5 pathway. Phytomedicine. 2024 Mar;125:155359. doi: 10.1016/j.phymed.2024.155359. Epub 2024 Jan 24.
Ref 2 m(6)A eraser ALKBH5 mitigates the apoptosis of cardiomyocytes in ischemia reperfusion injury through m(6)A/SIRT1 axis. PeerJ. 2023 May 11;11:e15269. doi: 10.7717/peerj.15269. eCollection 2023.
Ref 3 Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
Ref 4 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 5 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69. doi: 10.1177/1087057111422103. Epub 2011 Nov 15.
Ref 6 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 7 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
Ref 8 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 9 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 10 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
Ref 11 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 12 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 13 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 14 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 15 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 16 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 17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 18 ClinicalTrials.gov (NCT00615966) Phase 2 Study of the Safety of Diannexin in Kidney Transplant Recipients. U.S. National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT02103959) Safety and Efficacy of CMX-2043 for Protection of the Heart and Kidneys in Subjects Undergoing Coronary Angiography. U.S. National Institutes of Health.
Ref 20 Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60.