Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05181
[1]
Non-coding RNA miR-218-5p FTO  lncRNA       miRNA   circRNA Direct Inhibition m6A modification MYC MYC FTO Demethylation : m6A sites
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
m6A Target Myc proto-oncogene protein (MYC)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-218-5p microRNA View Details
Regulated Target FTO alpha-ketoglutarate dependent dioxygenase (FTO) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited hsa-miR-218-5p to elevate FTO and Myc proto-oncogene protein (MYC). Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer
Responsed Disease Colorectal cancer ICD-11: 2B91
In-vitro Model
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
In-vivo Model Liver metastasis model construction: 2 × 106 CRC cells were injected into the tail vein of nude mice.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Myc proto-oncogene protein (MYC) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name AVI-5126 Phase 2 [2]
Synonyms
Resten-CP; NeuGene (CABG), AVI
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External Link
 Compound Name Resten-NG Phase 2 [3]
Synonyms
Resten-NG (TN)
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External Link
 Compound Name TWS-119 Investigative [4]
Synonyms
TWS119; 601514-19-6; 3-[[6-(3-Aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol; TWS 119; GSK inhibitor XII; GSK-3beta Inhibitor XII, TWS119; Neurogenesis Inducer, TWS119; CHEMBL405759; 3-(6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenol; 3-((6-(3-AMINOPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)OXY)PHENOL; 3-{[6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}phenol; Phenol, 3-[[6-(3-aminophenyl)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]-; K00245; MLS006011018; GTPL5980; SCHEMBL5559045; GSK-3BETA INHIB
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External Link
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [5]
Synonyms
INCMGA0012; Retifanlimab
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External Link
 Compound Name Aflibercept Approved [6]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
 Compound Name Regorafenib Approved [7]
Synonyms
755037-03-7; BAY 73-4506; Regorafenibum; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; BAY73-4506; Regorafenib (BAY 73-4506); UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); BAY73-4506 hydrochloride; Regorafenib [USAN:INN]
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 Compound Name Bevacizumab Approved [8]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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 Compound Name SYM-004 Phase 3 [8]
Synonyms
Chimeric IgG1 antibody 1024 (cancer), Symphogen; Chimeric IgG1 antibody 992 (cancer), Symphogen; Chimeric IgG1 antibodies992 + 1024 (cancer), Symphogen
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 Compound Name Bevacizumab + Erlotinib Phase 3 [9]
External Link
 Compound Name CPI-613 Phase 3 [8]
Synonyms
95809-78-2; 6,8-bis(benzylthio)octanoic acid; CPI 613; MLS006010202; SCHEMBL1062218; 6,8-Bis(benzylsulfanyl)octanoic acid; Octanoic acid, 6,8-bis((phenylmethyl)thio)-; Octanoic acid, 6,8-bis[(phenylMethyl)thio]-; 6,8-Bis[(phenylmethyl)thio]octanoic acid; CPI613; CHEMBL3186849; QCR-193; AOB1058; MolPort-023-219-128; HMS3656L06; C22H28O2S2; BCP04663; EX-A2043; s2776; AKOS025142095; BCP9000552; DB12109; RL06062; CS-0961; NCGC00344764-01; SMR004701300; AS-16613; BC261916; AK174899; HY-15453; BCP0726000030; KB-293127; AB0035874
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 Compound Name Bevacizumab Approved [6]
External Link
 Compound Name AlloStim Phase 2/3 [10]
Synonyms
AlloStim (TN)
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External Link
 Compound Name Sibrotuzumab Phase 2 [11]
External Link
 Compound Name CV301 Phase 2 [12]
External Link
 Compound Name Efatutazone Phase 2 [13]
Synonyms
Inolitazone; 223132-37-4; 5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-2,4-Thiazolidinedione; Efatutazone [INN]; RS5444; CS-7017; SCHEMBL3246054; CHEMBL3545280; JCYNMRJCUYVDBC-UHFFFAOYSA-N; Efatutazone;CS-7017;RS5444; BCP07478; AKOS030526729; DB11894; CS-0778; KB-77905; DA-07988; HY-14792; QC-10456; 4CA-1384; FT-0737589; 5-[4-[6-(4-amino-3 ,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione
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 Compound Name LOR-2040 Phase 2 [14]
External Link
 Compound Name RG7221 Phase 2 [15]
External Link
 Compound Name PEG-SN38 Phase 2 [16]
Synonyms
EZN-2208
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External Link
 Compound Name MEGF0444A Phase 2 [17]
External Link
 Compound Name Encapsulated cell therapy Phase 1/2 [18]
External Link
 Compound Name AB928 Phase 1/2 [19]
External Link
 Compound Name MGD007 Phase 1 [15]
External Link
 Compound Name BNC-101 Phase 1 [20]
External Link
 Compound Name Navicixizumab Phase 1 [8]
External Link
 Compound Name RG7160 Discontinued in Phase 2 [21]
External Link
 Compound Name Nimesulide Terminated [22]
Synonyms
51803-78-2; N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide; Mesulid; Flogovital; Sulidene; Nimed; R-805; 4-NITRO-2-PHENOXYMETHANESULFONANILIDE; Nisulid; Nimesulidum [INN-Latin]; Nimesulida [INN-Spanish]; R 805; UNII-V4TKW1454M; 4-Nitro-2-phenoxy-methanesulfonanilide; 4'-Nitro-2'-phenoxymethanesulfonanilide; Methanesulfonamide, N-(4-nitro-2-phenoxyphenyl)-; EINECS 257-431-4; 4'-Nitro-2'-phenoxymethansulfonanilid; BRN 2421175; CHEMBL56367; MLS000069680; V4TKW1454M; Methanesulfonanilide, 4'-nitro-2'-phenoxy-; CHEBI:44445; Dulanermin
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 Compound Name Saracatinib Phase 2 [23]
External Link
 Compound Name G3139 + Irinotecan Investigative [24]
External Link
References
Ref 1 Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer. Cell Biol Toxicol. 2023 Dec;39(6):2551-2568. doi: 10.1007/s10565-023-09837-2. Epub 2023 Nov 14.
Ref 2 Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the inhibition of corneal transplant rejection in a rat cornea transplant model. J Ocul Pharmacol Ther. 2012 Apr;28(2):194-201. doi: 10.1089/jop.2011.0135. Epub 2011 Dec 7.
Ref 3 Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model. Catheter Cardiovasc Interv. 2001 Oct;54(2):247-56. doi: 10.1002/ccd.1277.
Ref 4 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.
Ref 5 Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway.J Med Chem. 2019 Feb 28;62(4):1715-1730.
Ref 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 5891).
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 12 ClinicalTrials.gov (NCT03547999) A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC. U.S. National Institutes of Health.
Ref 13 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 14 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 15 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 16 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 17 ClinicalTrials.gov (NCT00909740) A Study of the Safety and Pharmacokinetics of MEGF0444A Administered to Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 18 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 19 ClinicalTrials.gov (NCT04660812) An Open Label Study Evaluating the Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 20 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 21 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029052)
Ref 22 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 23 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 24 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.