m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03278
 [1], [2]
Histone modification H3K4me3 KDM5C METTL14 Direct Inhibition m6A modification IFN-gamma IFN-gamma METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target Interferon gamma (IFN-gamma)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 5C (KDM5C) ERASER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene METTL14 View Details
Crosstalk Relationship Histone modification  →  m6A Inhibition
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, KDM5C-mediated demethylation of Histone H3 lysine 36 trimethylation (H3K36me3) in the promoter of METTL14 inhibited METTL14 transcription. In colorectal cancer, Mettl3- or METTL14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or METTL14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model
 NCM460 Normal Homo sapiens CVCL_0460
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 Colon cancer Mus musculus CVCL_A8EZ
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
In-vivo Model All animal experiments were approved by the animal care Committee of Nanjing First Hospital, Nanjing Medial University (acceptance No. SYXK 20160006). 2 × 106 transfected HCT116 cells in 0.2 ml PBS were injected into the tail vein of nude mice which were randomly divided into nine groups (eight mice per group). After 2 months of injection, mice were sacrificed, and their lungs were removed and stained by Hematoxylin and Eosin (HE) Staining.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Interferon gamma (IFN-gamma) 10 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Emapalumab Approved [3]
Synonyms
Emapalumab [INN]; Emapalumab [USAN:INN]; UNII-3S252O2Z4X; 3S252O2Z4X
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MOA Modulator
External Link
TTD: D0UI7K
 Compound Name Fumaric acid Phase 3 [4]
Synonyms
Fum; Fumarsaeure; Acidum fumaricum; Allomaleic acid; Allomalenic acid; Ammonium fumarate; Boletic acid; Butenedioic acid; Kyselina fumarova; Kyselina fumarova [Czech]; Lichenic acid; Tumaric acid; F0067; OR17920; FC 33 (acid); Fumarate, 10; Fumaric acid (8CI); Fumaric acid (NF); Lichenic acid (VAN); S04-0167; Trans-Butenedioic acid; U-1149; E-2-Butenedioic acid; Trans-2-Butenedioic acid; USAF EK-P-583; Trans-1,2-Ethylenedicarboxylic acid; Trans-but-2-enedioic acid; (2E)-2-butenedioic acid; (2E)-but-2-enedioic acid; (E)-2-Butenedioic acid; 1,2-Ethylenedicarboxylic acid, (E); 2-(E)-Butenedioic acid; 2-Butenedioic acid; 2-Butenedioic acid (2E-(9CI)
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MOA Binder
External Link
CID: 444972
TTD: D03GOO
DrugBank: DB01677
 Compound Name VIR-201 Phase 1/2 [5]
MOA Modulator
External Link
TTD: D0I5QV
 Compound Name AMG 811 Phase 1 [6]
MOA Modulator
External Link
TTD: D06FLP
 Compound Name CIGB-128 Phase 1 [7]
Synonyms
HeberPAG; IFN alpha2b + IFN gamma (injectable, skin cancer), CIGB
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MOA Modulator
External Link
TTD: D06NDP
 Compound Name TAK-603 Discontinued in Phase 2 [8]
MOA Modulator
External Link
CID: 153980
TTD: D0H6PX
 Compound Name Fontolizumab Discontinued in Phase 2 [9]
Synonyms
Fontolizumab (USAN/INN)
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External Link
TTD: D0N4ND
 Compound Name TG-1042 Discontinued in Phase 2 [10]
Synonyms
TG-1041; Adv-IFN-gamma; Adenovirus-interferon gamma based therapy (basal cell carcinoma), Virax; Adenovirus-interferon gamma based therapy (cancer), Transgene; Ad-IFN-gamma (basal cell carcinoma), Virax; Ad-IFN-gamma (lymphoma), Transgene
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MOA Modulator
External Link
TTD: D0Z9MR
 Compound Name CRx-191 Discontinued in Phase 2 [11]
MOA Inhibitor
External Link
TTD: D0VA2I
 Compound Name VPM-4-001 Preclinical [12]
Synonyms
Allogenic LNCaP cell vaccine (prostate tumor), Vakzine Projekt Management; Cell vaccine (prostate cancer), Vakzine Projekt Management; Allogenic LNCaP cells (IL-2, IFN-gamma), Vakzine Projekt Management
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External Link
TTD: D0WD6K
Lysine-specific demethylase 5C (KDM5C) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PBIT Investigative [13]
Synonyms
2514-30-9; 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one; 2-(4-methylphenyl)-1,2-benzothiazol-3-one; MLS000583746; 2-(p-Tolyl)benzo[d]isothiazol-3(2H)-one; 2-(p-tolyl)-1,2-benzothiazol-3-one; SMR000200989; 2-(4-methylphenyl)-1,2-benzothiazol-3(2H)-one; 1,2-Benzisothiazol-3(2H)-one, 2-(4-methylphenyl)-; 2-(4-methylphenyl)-2,3-dihydro-1,2-benzothiazol-3-one; ChemDiv3_007090; AC1LIP69; cid_935415; SCHEMBL2443755; GTPL7026; CHEMBL1336959; CTK0J4356; BDBM34737; AOB6896; DTXSID10359056; MolPort-002-285-696; HMS2576N21
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MOA Inhibitor
External Link
CID: 935415
TTD: D0IQ7Y
 Compound Name IOX2 Investigative [14]
Synonyms
compound 6
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MOA Inhibitor
External Link
CID: 54685215
TTD: D0WA3E
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [15]
Synonyms
INCMGA0012; Retifanlimab
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External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [16]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
TTD: D0C9ET
 Compound Name Regorafenib Approved [17]
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 [18]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
TTD: D04KBL
 Compound Name SYM-004 Phase 3 [18]
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 [19]
External Link
TTD: D09BKY
 Compound Name CPI-613 Phase 3 [18]
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 [16]
External Link
TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [20]
Synonyms
AlloStim (TN)
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External Link
TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [21]
External Link
TTD: DVX3H0
 Compound Name CV301 Phase 2 [22]
External Link
TTD: D9LT5G
 Compound Name Efatutazone Phase 2 [23]
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 [24]
External Link
TTD: D0I7NG
 Compound Name RG7221 Phase 2 [25]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [26]
Synonyms
EZN-2208
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External Link
CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [27]
External Link
TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [28]
External Link
TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [29]
External Link
CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [25]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [30]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [18]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [31]
External Link
TTD: D0E2CQ
 Compound Name Nimesulide Terminated [32]
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 [33]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [34]
External Link
CID: 91865905
TTD: D05IAN
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