m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03254
 [1]
m6A modification HDAC5 HDAC5 METTL3 Methylation : m6A sites Direct Enhancement Histone modification H3K14ac HDAC5 MIR142
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Histone deacetylase 5 (HDAC5)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone deacetylase 5 (HDAC5) ERASER View Details
Regulated Target Histone H3 lysine 14 acetylation (H3K14ac) View Details
Downstream Gene MIR142 View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary METTL3 upregulated histone deacetylase 5 (Histone deacetylase 5 (HDAC5)) expression in OS cells by increasing the m6A level. HDAC5 reduced the enrichment of H3K9ac/Histone H3 lysine 14 acetylation (H3K14ac) on MIR142 promoter, thus suppressing miR-142-5p expression and upregulating armadillo-repeat-containing 8 (ARMC8) level.
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
In-vitro Model
 U2OS Osteosarcoma Homo sapiens CVCL_0042
HOS Osteosarcoma Homo sapiens CVCL_0312
SaOS-2 Osteosarcoma Homo sapiens CVCL_0548
hFOB 1.19 Normal Homo sapiens CVCL_3708
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone deacetylase 5 (HDAC5) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID29671355-Compound-45a Patented [2]
MOA Inhibitor
Activity IC50 = 23 nM
External Link
CID: 86302836
TTD: D0YN2T
 Compound Name PMID29671355-Compound-23 Patented [2]
MOA Inhibitor
Activity IC50 = 1570 nM
External Link
CID: 118884610
TTD: D00HXJ
 Compound Name PMID29671355-Compound-67 Patented [2]
MOA Inhibitor
Activity IC50 = 170 nM
External Link
CID: 60201048
TTD: D0M0RE
 Compound Name PMID29671355-Compound-31 Patented [2]
MOA Inhibitor
Activity IC50 = 352 nM
External Link
CID: 90479372
TTD: D0DI9S
DrugBank: DB14979
 Compound Name PMID29671355-Compound-62 Patented [2]
MOA Inhibitor
Activity IC50 = 100 to 500 nM
External Link
TTD: D07WAT
 Compound Name PMID29671355-Compound-43 Patented [2]
MOA Inhibitor
Activity IC50 > 100000 nM
External Link
CID: 118515590
TTD: D0BP8I
 Compound Name PMID29671355-Compound-25 Patented [2]
MOA Inhibitor
Activity IC50 = 508 nM
External Link
CID: 126569528
TTD: D0RA0D
 Compound Name TMP269 Investigative [3]
Synonyms
TMFO1; compound 1 [PMID: 23524983]; TMP-269; TMP 269
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 80 nM
External Link
CID: 53344908
TTD: D0R7JA
2B51: Osteosarcoma 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Cisplatin Approved [4]
Synonyms
Abiplatin; Biocisplatinum; Briplatin; Cismaplat; Cisplatine; Cisplatino; Cisplatinum; Cisplatyl; Citoplationo; Lederplatin; Neoplatin; Plastin; Platamine; Platidiam; Platinoxan; Randa; Cis-DDP; Cis-Diamminedichloroplatinum; Peyrone's chloride; Peyrone's salt; Cis-Dichlorodiammineplatinum(II); Cis-[PtCl2(NH3)2]; Cis-diamminedichloridoplatinum(II); Trans-diamminedichloridoplatinum(II); (SP-4-1)-diamminedichloridoplatinum; (SP-4-1)-diamminedichloroplatinum; (SP-4-2)-diamminedichloridoplatinum; (SP-4-2)-diamminedichloroplatinum; Cisplatin (Chemotherapy)
    Click to Show/Hide
External Link
CID: 5702198
TTD: D0U5HU
 Compound Name Naxitamab Phase 2 [4]
External Link
TTD: D0HI5D
 Compound Name Tideglusib Phase 2 [5]
Synonyms
NP-031112; NP-12; NP031112; Tideglusib(NP-031112)
    Click to Show/Hide
External Link
CID: 11313622
TTD: D0UT7X
DrugBank: DB12129
 Compound Name Hu3F8 mAb Phase 2 [6]
External Link
TTD: D0R4UA
 Compound Name Saracatinib Phase 2 [7]
Synonyms
H8H; AZD-0530; Saracatinib, AZD-0530, AZD0530; N-(5-Chloro-1,3-benzodioxol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine
    Click to Show/Hide
External Link
CID: 10302451
TTD: D0M0XB
DrugBank: DB11805
 Compound Name ALMB-0168 Phase 1/2 [8]
External Link
TTD: DXAI94
 Compound Name AU101 Phase 1/2 [9]
External Link
TTD: D0T9JW
 Compound Name [153Sm]CycloSam Phase 1 [10]
External Link
TTD: D8W1DJ
 Compound Name GD2 T cells Phase 1 [11]
External Link
TTD: D0QB7N
 Compound Name Anti-GD2-CAR engineered T cells Phase 1 [12]
External Link
TTD: D09DND
 Compound Name Robatumumab Discontinued in Phase 2 [13]
External Link
TTD: D0X9RN
 Compound Name DG-8 Investigative [14]
Synonyms
DH-9; PPAR gamma agonists (osteosarcoma/ADPKD); PPAR gamma agonists (osteosarcoma/ADPKD), Chinese Academy of Sciences
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External Link
TTD: D0L3VC
References
Ref 1 METTL3 stabilizes HDAC5 mRNA in an m(6)A-dependent manner to facilitate malignant proliferation of osteosarcoma cells. Cell Death Discov. 2022 Apr 8;8(1):179. doi: 10.1038/s41420-022-00926-5.
Ref 2 HDAC inhibitors: a 2013-2017 patent survey. Expert Opin Ther Pat. 2018 Apr 19:1-17. doi: 10.1080/13543776.2018.1459568. Online ahead of print.
Ref 3 Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013 May;9(5):319-25. doi: 10.1038/nchembio.1223. Epub 2013 Mar 24.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 Evidence for irreversible inhibition of glycogen synthase kinase-3Beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904. doi: 10.1074/jbc.M111.306472. Epub 2011 Nov 18.
Ref 6 ClinicalTrials.gov (NCT02502786) Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma.
Ref 7 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. (Ligand id: 7731).
Ref 8 ClinicalTrials.gov (NCT04886765) A Phase I/II, Multi-center, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of ALMB-0168 in Patients With Osteosarcoma. U.S.National Institutes of Health.
Ref 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 10 ClinicalTrials.gov (NCT03612466) A Dose Finding Study of CycloSam Combined With External Beam Radiotherapy. U.S. National Institutes of Health.
Ref 11 ClinicalTrials.gov (NCT01953900) iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma
Ref 12 ClinicalTrials.gov (NCT02107963) A Phase I Trial of T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Children and Young Adults With GD2+ Solid Tumors
Ref 13 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027277)
Ref 14 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.