m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02056
 [1]
DNA methylation DNMT1 HOXD10 Indirect Inhibition m6A modification m6A Target m6A Target IGFBP3 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor-binding protein 3 (IGFBP3) READER
 Regulator Info 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1) WRITER View Details
Regulated Target Homeobox D10 (HOXD10) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary Functionally, Homeobox D10 (HOXD10) acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Responsed Drug 5-FU
 Drug Info 
Cell Process Cell proliferation
Cell colony formation
Cell migration
Cell invasion
In-vitro Model
 HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
DNA (cytosine-5)-methyltransferase 1 (DNMT1) 27 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name SGI110 Phase 3 [2]
MOA Modulator
External Link
CID: 137295284
TTD: D0Q5KZ
 Compound Name Guadecitabine Phase 3 [3]
Synonyms
UNII-2KT4YN1DP7; 929901-49-5; 2KT4YN1DP7; SGI-110 free acid; Guadecitabine [USAN:INN]; GuadecitabineSGI-110; Guadecitabine (USAN/INN); CHEMBL3544916; Guanosine, 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxy-; ZINC43203165; AKOS027321496; AKOS030238181; DB11918; CS-3089; HY-13542; D10877; 2'-deoxy-5-azacytidylyl-(3'-5')-2'-deoxyguanosine
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MOA Inhibitor
External Link
CID: 135564655
TTD: D0VZ4N
DrugBank: DB11918
 Compound Name CC-486 Phase 3 [4]
Synonyms
AG-14361; AG14361; 328543-09-5; UNII-48N0U0K50I; AG 14361; CHEMBL65892; 48N0U0K50I; Imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one, 2-[4-[(dimethylamino)methyl]phenyl]-5,6-dihydro-; AG-014361; 1-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one; Imidazo(4,5,1-jk)(1,4)benzodiazepin-7(4H)-one, 2-(4-((dimethylamino)methyl)phenyl)-5,6-dihydro-; 2-[4-[(Dimethylamino)methyl]phenyl]-5,6-dihydroimidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one; SMR000486393; MLS006011157; MLS001065917; Nucleoside analogue
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MOA Inhibitor
External Link
CID: 9840076
TTD: D09NTC
 Compound Name S-110 Phase 3 [5]
Synonyms
DNA demethylating agent (myelodysplastic syndrome), Supergen
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MOA Inhibitor
External Link
TTD: D0A2BO
 Compound Name Palifosfamide Phase 2 [6]
Synonyms
ZIO-201
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MOA Inhibitor
External Link
CID: 100427
TTD: D04FDN
DrugBank: DB05668
 Compound Name RX-3117 Phase 2 [7]
Synonyms
Antimetabolite (cancer), Rexahn; Antimetabolite (cancer), Rexahn/ Teva
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MOA Inhibitor
External Link
CID: 11242315
TTD: D0L7WS
 Compound Name Antroquinonol Phase 2 [8]
Synonyms
Hocena; Fungal extract (cancer), Golden Biotechnology
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MOA Inhibitor
External Link
CID: 24875259
TTD: D0T3AW
DrugBank: DB12326
 Compound Name GSK4172239 Phase 1 [9]
MOA Inhibitor
External Link
TTD: D5QR2M
 Compound Name PMID27376512-Compound-miR-155-5p Patented [10]
MOA Inhibitor
Activity Ki = 27.88 nM
External Link
TTD: D01CGQ
 Compound Name PMID27376512-Compound-Table1Example11 Patented [10]
MOA Inhibitor
Activity IC50 = 39440 nM
External Link
CID: 75201485
TTD: D04JIH
 Compound Name PMID27376512-Compound-Table1Example16 Patented [10]
MOA Inhibitor
Activity IC50 = 22520 nM
External Link
CID: 75201537
TTD: D05DSL
 Compound Name PMID27376512-Compound-Table1Example5 Patented [10]
MOA Inhibitor
Activity IC50(DNMT1) = 3530 nM
External Link
CID: 73774653
TTD: D09FMS
 Compound Name PMID27376512-Compound-asCEBP-2HPE Patented [10]
MOA Inhibitor
Activity Ki = 135.2 nM
External Link
TTD: D0E7OA
 Compound Name PMID27376512-Compound-asCEBP-1 Patented [10]
MOA Inhibitor
Activity Ki = 2003 nM
External Link
TTD: D0G6ON
 Compound Name PMID27376512-Compound-Table1Example4 Patented [10]
MOA Inhibitor
Activity IC50 = 13810 nM
External Link
CID: 75201432
TTD: D0K4YF
 Compound Name PMID27376512-Compound-asCEBP-2 Patented [10]
MOA Inhibitor
Activity Ki = 434.1 nM
External Link
TTD: D0KE4E
 Compound Name PMID27376512-Compound-asCEBP-1HPE Patented [10]
MOA Inhibitor
Activity Ki = 917.5 nM
External Link
TTD: D0LK4R
 Compound Name PMID27376512-Compound-Table1Example8 Patented [10]
MOA Inhibitor
Activity IC50 = 6850 nM
External Link
CID: 75201482
TTD: D0RT6C
 Compound Name PMID27376512-Compound-MTC-433 Patented [10]
MOA Inhibitor
Activity IC50 = 4.22 nM
External Link
TTD: D0U5CK
 Compound Name PMID27376512-Compound-Table1Example30 Patented [10]
MOA Inhibitor
External Link
CID: 75201638
TTD: D0YK6K
 Compound Name PMID27376512-Compound-MTC-424 Patented [10]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [10]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [10]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [10]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
 Compound Name PMX-700 Investigative [11]
Synonyms
SJ-005019; SJ-005059; DC-010-116; Temozolomide analogs (cancer), Pharminox
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MOA Modulator
External Link
TTD: D03DTQ
 Compound Name XB-05 Investigative [11]
MOA Inhibitor
External Link
TTD: D0JV8Q
 Compound Name CP-4200 Investigative [11]
Synonyms
Lipidated azacitidine (cancer, Lipid Vector), Clavis Pharma; 5-azacytidine-5'-elaidate
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MOA Inhibitor
External Link
TTD: D0OT1S
Insulin-like growth factor-binding protein 3 (IGFBP3) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Salvianolic acid B Phase 2 [12]
Synonyms
115939-25-8; 121521-90-2; Salvianolic-acid-B; Lithospermic acid B; MFCD07779133; (2R)-2-[(E)-3-[(2R,3R)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyl]oxy-3-(3,4-dihydroxyphenyl)propanoic acid; (R)-2-(((2R,3R)-4-((E)-3-((R)-1-Carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-en-1-yl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyl)oxy)-3-(3,4-dihydroxyphenyl)propanoic acid; Danshensuan B; Salcianolic acid B; C36H30O16; PubChem13035; CHEMBL3747259; ZINC49538629; AKOS015920258; AS-56980; S609; 939S258; (R)-2-((2R,3R)-4-((E)-3-((R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-enyl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyloxy)-3-(3,4-dihydroxyphenyl)propanoic acid; 1607436-77-0
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MOA Inhibitor
External Link
CID: 11629084
TTD: D2GV9Q
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [13]
Synonyms
INCMGA0012; Retifanlimab
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External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [14]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
TTD: D0C9ET
 Compound Name Regorafenib Approved [15]
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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External Link
CID: 11167602
TTD: D09GDD
DrugBank: DB08896
 Compound Name Bevacizumab Approved [3]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
TTD: D04KBL
 Compound Name SYM-004 Phase 3 [3]
Synonyms
Chimeric IgG1 antibody 1024 (cancer), Symphogen; Chimeric IgG1 antibody 992 (cancer), Symphogen; Chimeric IgG1 antibodies992 + 1024 (cancer), Symphogen
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External Link
TTD: D0CR8H
 Compound Name Bevacizumab + Erlotinib Phase 3 [16]
External Link
TTD: D09BKY
 Compound Name CPI-613 Phase 3 [3]
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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External Link
CID: 24770514
TTD: D07NVI
DrugBank: DB12109
 Compound Name Bevacizumab Approved [14]
External Link
TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [17]
Synonyms
AlloStim (TN)
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External Link
TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [18]
External Link
TTD: DVX3H0
 Compound Name CV301 Phase 2 [19]
External Link
TTD: D9LT5G
 Compound Name Efatutazone Phase 2 [20]
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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External Link
CID: 9832447
TTD: D0Y8NZ
DrugBank: DB11894
 Compound Name LOR-2040 Phase 2 [21]
External Link
TTD: D0I7NG
 Compound Name RG7221 Phase 2 [22]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [23]
Synonyms
EZN-2208
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External Link
CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [24]
External Link
TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [25]
External Link
TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [26]
External Link
CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [22]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [27]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [3]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [28]
External Link
TTD: D0E2CQ
 Compound Name Nimesulide Terminated [29]
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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External Link
CID: 4495
TTD: D0C0JT
DrugBank: DB04743
 Compound Name Saracatinib Phase 2 [30]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [31]
External Link
CID: 91865905
TTD: D05IAN
References
Ref 1 Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer. Front Oncol. 2021 Nov 1;11:771528. doi: 10.3389/fonc.2021.771528. eCollection 2021.
Ref 2 Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96.
Ref 5 S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010 May;9(5):1443-50.
Ref 6 Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84.
Ref 7 Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57.
Ref 8 Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential. J Agric Food Chem. 2014 Jun 18;62(24):5625-35.
Ref 9 Clinical pipeline report, company report or official report of GlaxoSmithKline
Ref 10 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 11 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: 2605).
Ref 12 Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3. J Mol Cell Cardiol. 2020 Feb;139:98-112.
Ref 13 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 14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 15 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 16 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 18 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 19 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 20 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 21 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 22 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 23 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 24 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 25 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 26 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 27 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 28 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 29 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 30 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 31 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.