m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05430
 [1]
m6A modification mmu-miR-7212-5p mmu-miR-7212-5p METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-7212-5p FGFR3  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target mmu-miR-7212-5p
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator mmu-miR-7212-5p microRNA View Details
Regulated Target Fibroblast growth factor receptor 3 (FGFR3) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of mmu-miR-7212-5p maturation. miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting Fibroblast growth factor receptor 3 (FGFR3).
Responsed Disease Unspecific body region injury ICD-11: ND56
 Disease Info 
Cell Process Cell differentiation
In-vitro Model
 MC3T3-E1 Normal Mus musculus CVCL_0409
In-vivo Model A longitudinal incision was made on the skin and the muscles were separated to expose the femur. A transverse osteotomy was performed in the mid-diaphysis of the femur, and the bones were stabilized by inserting a 23-gauge intramedullary needle. Equal amounts (100 uL) of phosphate-buffered saline (PBS), plasmid METTL3 and agomiR-7212-5p (10 mg/kg body weight) were locally injected into the femoral fracture site.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Fibroblast growth factor receptor 3 (FGFR3) 19 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Pemigatinib Approved [2]
Synonyms
Unii-Y6BX7BL23K; Y6BX7BL23K; GTPL9767; SCHEMBL15556271; HCDMJFOHIXMBOV-UHFFFAOYSA-N; example 126 [WO2014007951]; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one; 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2-one; INCB54828
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MOA Inhibitor
External Link
CID: 86705695
TTD: D0O6UY
DrugBank: DB15102
 Compound Name Trapidil Phase 4 [3]
Synonyms
Trapymin; Rocornal; 15421-84-8; Avantrin; Trapymine; N,N-diethyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine; AR 12008; Trapidilum [INN-Latin]; UNII-EYG5Y6355E; EINECS 239-434-2; BRN 0186842; 7-Diethylamino-5-methyl-s-triazolo(1,5-a)pyrimidine; MLS000567667; EYG5Y6355E; N,N-Diethyl-5-methyl-(1,2,4)triazolo(1,5-a)pyrimidine-7-amine; (1,2,4)Triazolo(1,5-a)pyrimidin-7-amine, N,N-diethyl-5-methyl-; 5-Methyl-7-diethylamino-s-triazolo-(1,5-a)-pyrimidine; NCGC00016715-01; AR-12008; SMR000154170; SU10991
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MOA Inhibitor
External Link
CID: 5531
TTD: D0U2CV
DrugBank: DB09283
 Compound Name BMS-582664 Phase 3 [4]
Synonyms
Brivanib alaninate; BMS 582664; BMS582664; BMS-582664, Brivanib alaninate; Brivanib alaninate (INN/USAN); L-Alanine, (1R)-2-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-5-methylpyrrolo(2,1-f)(1,2,4)triazin-6-yl)oxy)-1-methylethyl ester
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MOA Inhibitor
External Link
CID: 11154925
TTD: D03WQS
DrugBank: DB11865
 Compound Name TKI258 Phase 3 [4]
Synonyms
Dovitinib; 405169-16-6; CHIR-258; TKI-258; Chir 258; 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one; CHIR258; Dovitinib (TKI-258, CHIR-258); UNII-I35H55G906; CHEMBL522892; 804551-71-1; I35H55G906; TKI 258; 1027263-12-2; (3Z)-4-Amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]-2(3H)-quinolinone; C21H21FN6O; 4-Amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
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MOA Inhibitor
External Link
CID: 135611162
TTD: D07OZR
 Compound Name E-3810 Phase 3 [5]
Synonyms
Lucitanib; AL-3810; E-3810, EOS
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MOA Inhibitor
Activity IC50 = 237.5 nM
External Link
CID: 25031915
TTD: D02WVT
DrugBank: DB11845
 Compound Name B-701 Phase 2 [6]
Synonyms
VKRFJPYJBOIVPD-UHFFFAOYSA-N; B 701; NSC 46406; 78218-88-9; Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)-, (3-chloropropyl) ester; AC1L3VIX; AC1Q6T2K; NSC46406; NSC-46406; 3-chloropropyl n,n-bis(2-chloroethyl)-n'-(3-hydroxypropyl)phosphorodiamidate; LS-107974; 3-[[bis(2-chloroethyl)amino-(3-chloropropoxy)phosphoryl]amin; 3-[[bis(2-chloroethyl)amino-(3-chloropropoxy)phosphoryl]amino]propan-1-ol; Phosphorodiamidic acid,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)-, 3-chloropropyl ester
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MOA Antagonist
External Link
CID: 95987
TTD: D0G6CF
 Compound Name Recifercept Phase 2 [7]
Synonyms
TA-46
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External Link
TTD: DBA40S
 Compound Name Debio 1347 Phase 2 [8]
MOA Inhibitor
Activity IC50 = 22 nM
External Link
CID: 66555680
TTD: D0XT0W
DrugBank: DB12903
 Compound Name AEE-788 Phase 1/2 [4]
Synonyms
AEE; AEE 788; AEE788; GNF-Pf-5343; AEE-788, NVP-AEE 788, AEE788
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MOA Inhibitor
External Link
CID: 10297043
TTD: D0G2QH
DrugBank: DB12558
 Compound Name MK-2461 Phase 1/2 [9]
Synonyms
MK 2461
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MOA Inhibitor
Activity IC50 = 50 nM
External Link
CID: 44137946
TTD: D00DRL
 Compound Name Anti-FGFR3 Phase 1 [10]
External Link
TTD: D0V0BO
 Compound Name SAR442501 Phase 1 [11]
External Link
TTD: D9FMA2
 Compound Name PD-0183812 Terminated [12]
Synonyms
PETCVZZPKYJZAU-UHFFFAOYSA-N; PD183812; AC1NS8PJ; CHEMBL139653; SCHEMBL5268115; BDBM6280; PD 0183812; N8 Pyrido[2,3-d]pyrimidin-7-one deriv 72; 8-{bicyclo[221]heptan-2-yl}-2-({4-[4-(3-hydroxypropyl)piperidin-1-yl]phenyl}amino)-7H,8H-pyrido[2,3-d]pyrimidin-7-one; 8-(3-bicyclo[221]heptanyl)-2-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]pyrido[2,3-d]pyrimidin-7-one; PD0183813
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MOA Inhibitor
External Link
CID: 5330258
TTD: D0Z0KD
 Compound Name AV-370 Investigative [13]
Synonyms
Anti-FGF3 receptor antibody (cancer), AVEO Pharmaceuticals
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External Link
TTD: D03HGW
 Compound Name SU5402 Investigative [3]
Synonyms
215543-92-3; SU 5402; SU-5402; 3-[3-(2-Carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone; (Z)-3-(4-methyl-2-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrol-3-yl)propanoic acid; CHEMBL89363; 3-[(3-(2-CARBOXYETHYL)-4-METHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE; J-502595; 3-{[3-(2-carboxyethyl)-4-methylpyrrol-2-yl]methylene}-2-indolinone; 3-[4-methyl-2-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid; (Z)-3-(4-Methyl-2-((2-oxoindolin-3-ylidene)-methyl)-1H-pyrrol-3-yl)propanoic acid
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MOA Inhibitor
External Link
CID: 5289418
TTD: D0A4XJ
DrugBank: DB08577
 Compound Name 5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol Investigative [14]
Synonyms
9-Hydroxyellipticine; 9-Hydroxyellipticin; 51131-85-2; Hydroxyellipticine; ELLIPTICINE, 9-HYDROXY-; UNII-9G4A3ET6XG; IGIG 929; Hydroxy-9 ellipticine [French]; EINECS 257-000-0; NSC 237070; NSC 210717; 9G4A3ET6XG; CHEMBL26559; CHEBI:88297; C17H14N2O; 5,11-Dimethyl-6H-pyrido(4,3-b)carbazol-9-ol; 6H-Pyrido(4,3-b)carbazol-9-ol, 5,11-dimethyl-; 6H-Pyrido[4,3-b]carbazol-9-ol, 5,11-dimethyl-; 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole; Hydroxy-9 ellipticine
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MOA Inhibitor
Activity IC50 = 400 nM
External Link
CID: 91643
TTD: D05FFB
 Compound Name ACTB-1003 Investigative [13]
Synonyms
Multi-mode kinase inhibitor (oral, cancer), ACT Biotech; Multi-mode kinase inhibitor (oral, cancer), Bayer
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MOA Inhibitor
External Link
CID: 23653175
TTD: D0R6OM
 Compound Name PMID21493067C1d Investigative [15]
Synonyms
GTPL8123; BDBM50343726
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MOA Inhibitor
Activity IC50 = 115 nM
External Link
CID: 53232451
TTD: D02NNT
 Compound Name Ro-4396686 Investigative [16]
Synonyms
SCHEMBL5809947; CHEMBL606964
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MOA Inhibitor
External Link
CID: 11396738
TTD: D09XIL
ND56: Unspecific body region injury 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name ONO-4819 Discontinued in Phase 2 [17]
Synonyms
Rivenprost; AE1-734; ONO-4819CD; ONO-4819.CD; ONO-AE1-734
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External Link
CID: 9803828
TTD: D0O4XW
References
Ref 1 Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing. J Cell Mol Med. 2020 Jun;24(11):6385-6396. doi: 10.1111/jcmm.15284. Epub 2020 Apr 19.
Ref 2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
Ref 3 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278.
Ref 4 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
Ref 5 E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405. doi: 10.1158/0008-5472.CAN-10-2700. Epub 2011 Jan 6.
Ref 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. PLoS One. 2020 Dec 28;15(12):e0244368.
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. doi: 10.1158/0008-5472.CAN-09-2541. Epub 2010 Feb 9.
Ref 10 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 11 Clinical pipeline report, company report or official report of Sanofi
Ref 12 Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16. doi: 10.1021/jm000271k.
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: 1810).
Ref 14 Molecular modeling of wild-type and D816V c-Kit inhibition based on ATP-competitive binding of ellipticine derivatives to tyrosine kinases. J Med Chem. 2005 Oct 6;48(20):6194-201. doi: 10.1021/jm050231m.
Ref 15 In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61.
Ref 16 Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. doi: 10.1016/j.bmcl.2005.12.092. Epub 2006 Feb 3.
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. (Ligand id: 1930).