m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03042
|
[1] | |||
m6A modification
SETD2
SETD2
METTL3
Methylation
: m6A sites
Direct
Inhibition
Histone modification
H3K36me3
SETD2
VGF
|
|||||
| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | Methyltransferase-like 3 (METTL3) | WRITER | |||
| m6A Target | Histone-lysine N-methyltransferase SETD2 (SETD2) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | Histone modification (HistMod) | ||||
| Epigenetic Regulator | Histone-lysine N-methyltransferase SETD2 (SETD2) | WRITER | View Details | ||
| Regulated Target | Histone H3 lysine 36 trimethylation (H3K36me3) | View Details | |||
| Downstream Gene | VGF | View Details | |||
| Crosstalk Relationship | m6A → Histone modification | Inhibition | |||
| Crosstalk Mechanism | m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes | ||||
| Crosstalk Summary | METTL3 knockdown also reduced VGF expression by increasing Histone H3 lysine 36 trimethylation (H3K36me3) modification at the VGF promoter. Further research revealed that METTL3 knockdown upregulated the expression of histone methylase Histone-lysine N-methyltransferase SETD2 (SETD2), the major H3K36me3 methyltransferase, by methylating the m6A site in the 3'UTR of SETD2 mRNA in LUAD cells. | ||||
| Responsed Disease | Lung cancer | ICD-11: 2C25 | |||
In-vitro Model |
A-549 | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | |
|
HBE1
|
N.A. | Homo sapiens | CVCL_0287 | ||
| In-vivo Model | For the in vivo tumor formation assay, transfected A549 cells (1 × 107) were injected subcutaneously into the right thigh of female BALBc nude mice. | ||||
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
| 2C25: Lung cancer | 52 Compound(s) Regulating the Disease | Click to Show/Hide the Full List | ||
| Adagrasib | Approved | [2] | ||
| Synonyms |
2326521-71-3; MRTX-849; UNII-8EOO6HQF8Y; 8EOO6HQF8Y; 2-((S)-4-(7-(8-Chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile; CHEMBL4594350; SCHEMBL20974691; GTPL10888; Kras G12C inhibitor MRTX849; BCP31538; EX-A3258; MRTX 849; MFCD32263433; s8884; compound 20 [PMID: 32250617]; BS-16211; HY-130149; CS-0105265; 2-Piperazineacetonitrile, 4-(7-(8-chloro-1-naphthalenyl)-5,6,7,8-tetrahydro-2-(((2S)-1-methyl-2-pyrrolidinyl)methoxy)pyrido(3,4-d)pyrimidin-4-yl)-1-(2-fluoro-1-oxo-2-propen-1-yl)-, (2S)-
Click to Show/Hide
|
|||
| External Link | ||||
| Amivantamab | Approved | [3] | ||
| External Link | ||||
| Mobocertinib | Approved | [4] | ||
| Synonyms |
1847461-43-1; TAK-788; TAK788; AP32788; UNII-39HBQ4A67L; 39HBQ4A67L; propan-2-yl 2-[4-{[2-(dimethylamino)ethyl](methyl)amino}-2-methoxy-5-(prop-2-enamido)anilino]-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Mobocertinib [INN]; Mobocertinib [USAN]; AP-32788; Mobocertinib (TAK788); Mobocertinib(TAK-788); SCHEMBL17373133; GTPL10468; BDBM368374; BCP31045; EX-A3392; US10227342, Example 10; MFCD32669806; NSC825519; s6813; TAK-788;AP32788; WHO 11183; NSC-825519; example 94 [WO2015195228A1]; HY-135815; CS-0114256; TAK-788;TAK 788; AP 32788; 5-Pyrimidinecarboxylic acid, 2-((4-((2-(dimethylamino)ethyl)methylamino)-2-methoxy-5-((1-oxo-2-propen-1-yl)amino)phenyl)amino)-4-(1-methyl-1H-indol-3-yl)-, 1-methylethyl ester; C(C=C)(=O)NC=1C(=CC(=C(C=1)NC1=NC=C(C(=N1)C1=CN(C2=CC=CC=C12)C)C(=O)OC(C)C)OC)N(C)CCN(C)C; Isopropyl 2-((5-acrylamido-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Isopropyl 2-(5-acrylamido-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenylamino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Propan-2-yl 2-(5-(acryloylamino)-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyanilino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; propan-2-yl 2-[4-[2-(dimethylamino)ethyl-methylamino]-2-methoxy-5-(prop-2-enoylamino)anilino]-4-(1-methylindol-3-yl)pyrimidine-5-carboxylate
Click to Show/Hide
|
|||
| External Link | ||||
| Sugemalimab | Approved in China | [5] | ||
| External Link | ||||
| Sacituzumab govitecan | Approved | [6] | ||
| Synonyms |
1491917-83-9; 1535963-91-7; 1796566-95-4; CYSTEINYL CL2A-SN-38; DA64T2C2IO; DTXSID401335985; EX-A4354; F82944; GOVITECAN CYSTEINYL CONJUGATE; hRS 7SN38; hRS7-SN38; IMMU 132; IMMU-132; M9BYU8XDQ6; Sacituzumab govitecan; Sacituzumab govitecan [USAN]; sacituzumab-govitecan; Satralizumab linker; SN-38 CYSTEINYL CONJUGATE; UNII-M9BYU8XDQ6
Click to Show/Hide
|
|||
| External Link | ||||
| Atezolizumab | Approved | [7] | ||
| External Link | ||||
| Tepotinib | Approved | [8] | ||
| Synonyms |
1100598-32-0; EMD 1214063; UNII-1IJV77EI07; Tepotinib (EMD 1214063); EMD1214063; 1IJV77EI07; MSC-2156119J; Benzonitrile, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]-; C29H28N6O2; Tepotinib [INN]; Benzonitrile, 3-[1,6-Dihydro-1-[[3-[5-[(1-Methyl-4-Piperidinyl)Methoxy]-2-PyriMidinyl]Phenyl]Methyl]-6-Oxo-3-Pyridazinyl]; Benzonitrile, 3-(1,6-dihydro-1-((3-(5-((1-methyl-4-piperidinyl)methoxy)-2-pyrimidinyl)phenyl)methyl)-6-oxo
Click to Show/Hide
|
|||
| External Link | ||||
| Sotorasib | Approved | [9] | ||
| Synonyms |
AMG-510; AMG510; AMG-510 racemate; 2252403-56-6; AMG 510; Kras G12C inhibitor 9; 2296729-00-3; UNII-2B2VM6UC8G; 2B2VM6UC8G; CHEMBL4535757; 2296729-00-3 (racemate); 4-((S)-4-Acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one; 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-[(2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one; Sotorasib [INN]; 6-Fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-((2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl)pyrido(2,3-d)pyrimidin-2-one; AMG510 racemate; Sotorasib [USAN]; AMG-510(racemate); Kras mutant-targeting AMG 510; SCHEMBL20560375; GTPL10678; AMG 510 pound>>AMG-510; AMY16918; BCP30452; BCP33368; EX-A3538; BDBM50514402; NSC818433; s8830; WHO 11370; DB15569; NSC-818433; BS-16684; HY-114277; CS-0081316; compound (R)-38 [PMID: 31820981]; (1m)-6-Fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)-4-((2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl)pyrido(2,3-d)pyrimidin-2(1H)-one; (1S)-4-((S)-4-Acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one; 2296729-66-1; Pyrido(2,3-d)pyrimidin-2(1H)-one, 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(1-methylethyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl)-
Click to Show/Hide
|
|||
| External Link | ||||
| Entrectinib | Approved | [10] | ||
| Synonyms |
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
Click to Show/Hide
|
|||
| External Link | ||||
| Repotrectinib | Approved | [11] | ||
| Synonyms |
FIKPXCOQUIZNHB-RRKGBCIJSA-N; SCHEMBL20438940; TPX 0005; BCP19778
Click to Show/Hide
|
|||
| External Link | ||||
| MYL-1402O | Phase 3 | [12] | ||
| Synonyms |
bevacizumab biosimilar
Click to Show/Hide
|
|||
| External Link | ||||
| AB154 | Phase 3 | [13] | ||
| Synonyms |
Domvanalimab
Click to Show/Hide
|
|||
| External Link | ||||
| Datopotamab deruxtecan | Phase 3 | [14] | ||
| External Link | ||||
| CS1001 | Phase 3 | [15] | ||
| External Link | ||||
| JDQ443 | Phase 3 | [16] | ||
| Synonyms |
(S)-JDQ-443; 1-(6-((4S)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)prop-2-en-1-one; 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-inda zol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]- 2-Propen-1-one; 1-[6-[(4R)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]-2-propen-1-one; 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one; 1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5- methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2- azaspiro[3.3]heptan-2-yl}prop-2-en-1-one; 1-{6-[(4M)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one; 2653994-08-0; 2653994-10-4; 2-Propen-1-one, 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]-; AKOS040757949; AT36708; BDBM50579985; CHEMBL5077861; compound 5 [PMID: 35404998]; CS-0226220; CS-0311034; EX-A5693; example 1a [WO2021120890A1]; GLXC-25533; GTPL11715; HY-139612A; JDQ 443; JDQ 443 [WHO-DD]; JDQ443; JDQ-443; MS-29737; NSC846146; NSC-846146; NVP-JDQ443; NVP-JDQ-443; Opnurasib; opnurasib [INN]; -PROPEN-1-ONE, 1-(6-((4R)-4-(5-CHLORO-6-METHYL-1H-INDAZOL-4-YL)-5-METHYL-3-(1-METHYL-1H-INDAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-AZASPIRO(3.3)HEPT-2-YL)-; Q3W0H3V1LQ; SCHEMBL23533580
Click to Show/Hide
|
|||
| External Link | ||||
| TRS003 | Phase 3 | [17] | ||
| External Link | ||||
| Tusamitamab ravtansine | Phase 3 | [18] | ||
| Synonyms |
SAR408701
Click to Show/Hide
|
|||
| External Link | ||||
| RG6058 | Phase 3 | [19] | ||
| Synonyms |
Tiragolumab
Click to Show/Hide
|
|||
| External Link | ||||
| GSK4069889 | Phase 2 | [20] | ||
| Synonyms |
TSR-022
Click to Show/Hide
|
|||
| External Link | ||||
| APL-101 | Phase 2 | [21] | ||
| Synonyms |
Bozitinib; PLB-1001; 1440964-89-5; Vebreltinib; Vebreltinib [USAN]; UNII-2WZP8A9VFN; 2WZP8A9VFN; Bozitinib (PLB-1001); SCHEMBL15594471; BDBM107096; CBI-3103; s6762; WHO 11677; HY-125017; CS-0088607; US9695175, 44; 1,2,4-Triazolo(4,3-b)pyridazine, 6-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(difluoro(6- fluoro-2-methyl-2H-indazol-5-yl)methyl)-; 6-(1-Cyclopropyl-1H-pyrazol-4-yl)-3-(difluoro(6-fluoro-2-methyl-2H-indazol-5- yl)methyl)-1,2,4-triazolo(4,3-b)pyridazine
Click to Show/Hide
|
|||
| External Link | ||||
| SGN-LIV1A | Phase 2 | [22] | ||
| Synonyms |
Ladiratuzumab Vedotin
Click to Show/Hide
|
|||
| External Link | ||||
| BNT116 | Phase 2 | [23] | ||
| External Link | ||||
| AZD7789 | Phase 2 | [24] | ||
| External Link | ||||
| L-DOS47 | Phase 1/2 | [25] | ||
| External Link | ||||
| NC318 | Phase 2 | [26] | ||
| External Link | ||||
| Vorolanib | Phase 2 | [27] | ||
| Synonyms |
UNII-YP8G3I74EL; YP8G3I74EL; 1013920-15-4; (S,Z)-N-(1-(Dimethylcarbamoyl)pyrrolidin-3-yl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; Vorolanib [INN]; SCHEMBL2439528; CHEMBL4297587; N-((3S)-1-(dimethylcarbamoyl)pyrrolidin-3-yl)-5-((Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; s6843; DB15247; HY-109019; CS-0030517; Q27294638; 1H-Pyrrole-3-carboxamide, N-((3S)-1-((dimethylamino)carbonyl)-3-pyrrolidinyl)-5-((Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-
Click to Show/Hide
|
|||
| External Link | ||||
| Xofigo | Phase 2 | [28] | ||
| External Link | ||||
| Bintrafusp alfa | Phase 2 | [29] | ||
| External Link | ||||
| Voyager-V1 | Phase 2 | [30] | ||
| Synonyms |
VSV-IFNBeta-NIS
Click to Show/Hide
|
|||
| External Link | ||||
| AB-106 | Phase 2 | [31] | ||
| Synonyms |
DS6051b; GTPL11198; AB106
Click to Show/Hide
|
|||
| External Link | ||||
| RO-5126766 | Phase 2 | [32] | ||
| Synonyms |
VS-6766; CH-5126766; Dual Raf/MEK protein kinase inhibitor (cancer), Roche
Click to Show/Hide
|
|||
| External Link | ||||
| TC-210 | Phase 1/2 | [33] | ||
| External Link | ||||
| EMB-01 | Phase 1/2 | [34] | ||
| External Link | ||||
| NM21-1480 | Phase 1/2 | [35] | ||
| External Link | ||||
| MRx0518 | Phase 1/2 | [36] | ||
| External Link | ||||
| DZD9008 | Phase 1/2 | [37] | ||
| External Link | ||||
| BGB-A425 | Phase 1/2 | [38] | ||
| External Link | ||||
| Rilvegostomig | Phase 1/2 | [39] | ||
| Synonyms |
AZD2936
Click to Show/Hide
|
|||
| External Link | ||||
| IK-007 | Phase 1/2 | [40] | ||
| Synonyms |
grapiprant
Click to Show/Hide
|
|||
| External Link | ||||
| IBI318 | Phase 1 | [41] | ||
| External Link | ||||
| GEN-011 | Phase 1 | [42] | ||
| External Link | ||||
| ENV-105 | Phase 1 | [43] | ||
| Synonyms |
Carotuximab
Click to Show/Hide
|
|||
| External Link | ||||
| AMG 160 | Phase 1 | [44] | ||
| External Link | ||||
| ADP-A2M10 | Phase 1 | [45] | ||
| External Link | ||||
| MEDI5752 | Phase 1 | [46] | ||
| External Link | ||||
| PF-07104091 | Phase 1 | [47] | ||
| External Link | ||||
| PF-06936308 | Phase 1 | [48] | ||
| External Link | ||||
| GEM3PSCA | Phase 1 | [49] | ||
| External Link | ||||
| PF-07257876 | Phase 1 | [50] | ||
| External Link | ||||
| Cosibelimab | Phase 1 | [51] | ||
| Synonyms |
CK-301/TG-1501
Click to Show/Hide
|
|||
| External Link | ||||
| Gemcitabine | Approved | [52] | ||
| External Link | ||||
| SMI-4a | Investigative | [53] | ||
| Synonyms |
438190-29-5; SMI 4a; TCS PIM-1 4a; (Z)-SMI-4a; (Z)-5-(3-(trifluoromethyl)benzylidene)thiazolidine-2,4-dione; (5Z)-5-[3-(trifluoromethyl)benzylidene]-1,3-thiazolidine-2,4-dione; CHEMBL183906; (5Z)-5-[[3-(TRIFLUOROMETHYL)PHENYL]METHYLENE]-2,4-THIAZOLIDINEDIONE; (5Z)-5-[[3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione; 327033-36-3; C11H6F3NO2S; (Z)-5-(3-(Trifluoromethyl)benzylidene)-thiazolidine-2,4-dione; (5Z)-5-{[3-(trifluoromethyl)phenyl]methylidene}-1,3-thiazolidine-2,4-dione; Pim inhibitor 4a; 3vc4; SMI-4q; TCS PIM-1-4a; 5-(3-(Trifluoromethyl)benzylidene)thiazolidine-2,4-dione; 5-[3-(Trifluoromethyl)benzylidene]thiazolidine-2,4-dione; cc-717; thiazolidine-2,4-dione, 4a; SCHEMBL2541382; SCHEMBL2541388; BDBM26626; AOB6260; EX-A111; SYN1113; BDBM138364; HMS3229J21; 2720AH; HY-16576A; MFCD01152003; s8005; ZINC12576047; AKOS001314163; SMI-4a, >=98% (HPLC); CCG-265027; NCGC00345836-02; NCGC00345836-14; AC-32861; HY-15474; AB0165836; EC-000.2291; J3.561.866J; A11945; W-5256; US8877795, 12; Q27451064; 5-[[3-(trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione
Click to Show/Hide
|
|||
| External Link | ||||
References
: m6A sites