m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03592
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[1], [2] | |||
Histone modification
H3K4me3
SMYD2
LINC01605
Indirect
Enhancement
m6A modification
CCNE1
CCNE1
METTL3
Methylation
: m6A sites
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| m6A Modification: | |||||
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| m6A Regulator | Methyltransferase-like 3 (METTL3) | WRITER | |||
| m6A Target | G1/S-specific cyclin-E1 (CCNE1) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | Histone modification (HistMod) | ||||
| Epigenetic Regulator | N-lysine methyltransferase SMYD2 (SMYD2) | WRITER | View Details | ||
| Regulated Target | Histone H3 lysine 4 trimethylation (H3K4me3) | View Details | |||
| Downstream Gene | LINC01605 | View Details | |||
| Crosstalk Relationship | Histone modification → m6A | Enhancement | |||
| Crosstalk Mechanism | histone modification indirectly regulates m6A modification through downstream signaling pathways | ||||
| Crosstalk Summary | LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone Histone H3 lysine 4 trimethylation (H3K4me3) as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. METTL3 promotes colorectal cancer proliferation by stabilizing G1/S-specific cyclin-E1 (CCNE1) mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC. | ||||
| Responsed Disease | Colorectal cancer | ICD-11: 2B91 | |||
| Pathway Response | Cell cycle | hsa04110 | |||
| Cell Process | Cell proliferation | ||||
| Arrest cell cycle at G1 phase | |||||
In-vitro Model |
HT29 | Colon cancer | Mus musculus | CVCL_A8EZ | |
| LoVo | Colon adenocarcinoma | Homo sapiens | CVCL_0399 | ||
| In-vivo Model | LoVo cells (5 × 106 cells/ 200 uL PBS) stably transfected with METTL3 knockdown lentiviral vector or control vector were respectively injected subcutaneously into the left flank of each mouse. | ||||
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
| G1/S-specific cyclin-E1 (CCNE1) | 25 Compound(s) Regulating the Target | Click to Show/Hide the Full List | ||
| PD-0183812 | Terminated | [3] | ||
| 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 | ||||
| (2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| 2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol | Investigative | [5] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| 5-nitroindirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Fluoro-5'-methyl-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| (2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime | Investigative | [4] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| 3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol | Investigative | [5] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| aloisine A | Investigative | [6] | ||
| Synonyms |
4-(7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)phenol; 496864-16-5; RP107; 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE; CHEMBL75680; 7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP-107; ALH; 4-{7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl}phenol; 1ung; SCHEMBL80147; BDBM7377; GTPL5924; AC1NS169; 4-(7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol; CHEBI:93641; CTK8D4068; DTXSID30416115; HMS3229A14; RM-39; BCP26893; ZINC2540737; ACT06534; IN1539; HSCI1_000219; MFCD04973541; AKOS005145972; CCG-206814; DB07364; RTC-063070; AJ-39131
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| MOA | Inhibitor | |||
| External Link | ||||
| 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione | Investigative | [7] | ||
| Synonyms |
CHEMBL380598; SCHEMBL3148490; HVQJGNALTWNDMX-UHFFFAOYSA-N; BDBM50375058; 2-(1H-Indole-3-yl)-3-phenylmaleimide
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| MOA | Inhibitor | |||
| External Link | ||||
| BMS-536924 | Investigative | [8] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione | Investigative | [7] | ||
| Synonyms |
1H-Pyrrole-2,5-dione, 3,4-bis(4-methoxyphenyl)-; 108774-82-9; ACMC-20mbs9; CHEMBL381099; CTK0G2626; DTXSID90449388
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| MOA | Inhibitor | |||
| External Link | ||||
| 3,4-diphenyl-1H-pyrrole-2,5-dione | Investigative | [7] | ||
| Synonyms |
2,3-diphenylmaleimide; 1H-Pyrrole-2,5-dione, 3,4-diphenyl-; 31295-36-0; AC1MBL6S; SCHEMBL114611; CHEMBL201949; CTK1B9880; 3,4-diphenylpyrrole-2,5-dione; DTXSID70372903; ZINC3847556
Click to Show/Hide
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| MOA | Inhibitor | |||
| External Link | ||||
| 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione | Investigative | [7] | ||
| Synonyms |
CHEMBL372076; SCHEMBL3822337
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| MOA | Inhibitor | |||
| External Link | ||||
| 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Investigative | [5] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| N-lysine methyltransferase SMYD2 (SMYD2) | 6 Compound(s) Regulating the Target | Click to Show/Hide the Full List | ||
| AZ505 | Preclinical | [9] | ||
| Synonyms |
AZ 505; AZ-505
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| MOA | Inhibitor | |||
| Activity | IC50 = 120 nM | |||
| External Link | ||||
| LLY-507 | Preclinical | [10] | ||
| Synonyms |
1793053-37-8; LLY507; CHEMBL3414623; 5-Cyano-2'-{4-[2-(3-Methyl-1h-Indol-1-Yl)ethyl]piperazin-1-Yl}-N-[3-(Pyrrolidin-1-Yl)propyl]biphenyl-3-Carboxamide; 3-cyano-5-(2-{4-[2-(3-methyl-1H-indol-1-yl)ethyl]piperazin-1-yl}phenyl)-N-[3-(pyrrolidin-1-yl)propyl]benzamide; 3-Cyano-5-[2-[4-[2-(3-methyl-1H-indol-1-yl)ethyl]piperazin-1-yl]phenyl]-N-[3-(pyrrolidin-1-yl)propyl]benzamide; GTPL8239; SCHEMBL19760400; EX-A899; LLY 507; MolPort-042-624-530; BCP17114; s7575; BDBM50075102; ZINC231558920; AKOS027470175; CS-5126
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| MOA | Inhibitor | |||
| Activity | IC50 < 15 nM | |||
| External Link | ||||
| EPZ032597 | Preclinical | [11] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| EPZ033294 | Preclinical | [11] | ||
| MOA | Inhibitor | |||
| External Link | ||||
| A-893 | Preclinical | [12] | ||
| Synonyms |
1868232-32-9; (R)-N-cyclohexyl-3-((3,4-dichlorophenethyl)amino)-N-(2-((2-hydroxy-2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)amino)ethyl)propanamide; CHEMBL3590526; N-Cyclohexyl-N~3~-[2-(3,4-Dichlorophenyl)ethyl]-N-(2-{[(2r)-2-Hydroxy-2-(3-Oxo-3,4-Dihydro-2h-1,4-Benzoxazin-8-Yl)ethyl]amino}ethyl)-Beta-Alaninamide; SCHEMBL17476248; EX-A2769; BDBM50095537; AKOS030235552; ZINC230499113; ACN-037539; AC-29886; HY-19563; CS-0015655; Q27454706; 4GQ; N-Cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2R)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide
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| MOA | Inhibitor | |||
| External Link | ||||
| BAY 598 | Preclinical | [13] | ||
| Synonyms |
BAY-598; 1906919-67-2; CHEMBL3818617; 1906919-67-2 (S-isomer); (S,E)-N-(1-(N'-cyano-N-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; BAY 598 - Bio-X; BAY598; GTPL8953; EX-A1835; BDBM50180955; ZINC504786915; AC-31567; BS-16389; HY-19546; CS-0015642; J3.601.000B; Q27074893; (S)-N-(1-(N'-Cyano-N-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; (S,E)-N-(1-(N-cyano-N'-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; (S,Z)-N-(1-(N-cyano-N'-(3-(difluoromethoxy)phenyl)carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl)-N-ethyl-2-hydroxyacetamide; N-[(4S)-1-[(Cyanoamino)[[3-(difluoromethoxy)phenyl]imino]methyl]-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide; N-[(4S)-1-[(Z)-N'-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl]-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide
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| MOA | Inhibitor | |||
| External Link | ||||
| 2B91: Colorectal cancer | 25 Compound(s) Regulating the Disease | Click to Show/Hide the Full List | ||
| Retifanlimab | Approved | [14] | ||
| Synonyms |
INCMGA0012; Retifanlimab
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| Aflibercept | Approved | [15] | ||
| Synonyms |
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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| Regorafenib | Approved | [16] | ||
| 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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| Bevacizumab | Approved | [17] | ||
| Synonyms |
Bevacizumab (ophthalmic slow-release tissue tablet)
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| SYM-004 | Phase 3 | [17] | ||
| Synonyms |
Chimeric IgG1 antibody 1024 (cancer), Symphogen; Chimeric IgG1 antibody 992 (cancer), Symphogen; Chimeric IgG1 antibodies992 + 1024 (cancer), Symphogen
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| Bevacizumab + Erlotinib | Phase 3 | [18] | ||
| External Link | ||||
| CPI-613 | Phase 3 | [17] | ||
| 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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| Bevacizumab | Approved | [15] | ||
| External Link | ||||
| AlloStim | Phase 2/3 | [19] | ||
| Synonyms |
AlloStim (TN)
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| Sibrotuzumab | Phase 2 | [20] | ||
| External Link | ||||
| CV301 | Phase 2 | [21] | ||
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| Efatutazone | Phase 2 | [22] | ||
| 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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| LOR-2040 | Phase 2 | [23] | ||
| External Link | ||||
| RG7221 | Phase 2 | [24] | ||
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| PEG-SN38 | Phase 2 | [25] | ||
| Synonyms |
EZN-2208
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| MEGF0444A | Phase 2 | [26] | ||
| External Link | ||||
| Encapsulated cell therapy | Phase 1/2 | [27] | ||
| External Link | ||||
| AB928 | Phase 1/2 | [28] | ||
| External Link | ||||
| MGD007 | Phase 1 | [24] | ||
| External Link | ||||
| BNC-101 | Phase 1 | [29] | ||
| External Link | ||||
| Navicixizumab | Phase 1 | [17] | ||
| External Link | ||||
| RG7160 | Discontinued in Phase 2 | [30] | ||
| External Link | ||||
| Nimesulide | Terminated | [31] | ||
| 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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| Saracatinib | Phase 2 | [32] | ||
| External Link | ||||
| G3139 + Irinotecan | Investigative | [33] | ||
| External Link | ||||
References
: m6A sites