m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03578
 [1], [2]
Histone modification H3K27ac EP300 LINC01605 Indirect Enhancement m6A modification EphA2 EphA2 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Ephrin type-A receptor 2 (EphA2)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) 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-p300-mediated modifications of histone H3K4me3 as well as Histone H3 lysine 27 acetylation (H3K27ac). LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2. Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model
 HCT 116 Colon carcinoma Homo sapiens CVCL_0291
NCM460 Normal Homo sapiens CVCL_0460
HT29 Colon cancer Mus musculus CVCL_A8EZ
LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model A total of 8 × 106 wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Ephrin type-A receptor 2 (EphA2) 9 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CAR-T cells targeting EphA2 Phase 1/2 [3]
MOA CAR-T-Cell-Therapy
External Link
TTD: D05OHY
 Compound Name BT5528 Phase 1/2 [4]
External Link
TTD: DS5C0K
 Compound Name DS-8895 Phase 1 [5]
External Link
TTD: D03YBJ
 Compound Name MEDI-547 Phase 1 [6]
Synonyms
MedImmune, MedImmune/AstraZeneca
    Click to Show/Hide
External Link
TTD: D0B8MS
 Compound Name MEDI-543 Preclinical [7]
Synonyms
MEDI-EphA2; L/A Lm-MCMV vaccine, Cerus/MedImmune; Listeria monocytogenes-based immunotherapy (EphA2-targeting), Cerus; Listeria monocytogenes-based immunotherapy (EphA2-targeting), Cerus/MedImmune; Live-attenuated Listeria monocytogenes (Lm)-based vaccine (CMV), Cerus/MedImmune
    Click to Show/Hide
External Link
TTD: D0W8HP
 Compound Name PMID21561767C8h Investigative [8]
Synonyms
GTPL8170; BDBM50345579
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 0.6 nM
External Link
CID: 46864270
TTD: D02BXJ
 Compound Name PMID19788238C66 Investigative [9]
Synonyms
1192216-03-7; GTPL8141; ZINC45245466; NSC752203; BDBM50299218; NSC-752203; KB-65160
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MOA Inhibitor
Activity IC50 = 2.3 nM
External Link
CID: 44478401
TTD: D05FXD
 Compound Name AMP-PNP Investigative [10]
Synonyms
Phosphoaminophosphonic acid-adenylate ester; gamma-Imino-ATP; ADENYLYL IMIDODIPHOSPHATE; AMPPNP; Adenyl imidodiphosphate; 25612-73-1; adenyl-5'-yl imidodiphosphate; CHEBI:47785; App(NH)p; O(5')-(1,2-dihydroxy-2-phosphonoaminodiphosphoryl)adenosine; 5'-O-(hydroxy{[hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl)adenosine; [[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid; p(NH)Ppf; beta,gamma-Imido-ATP; beta,gamma-Imidoadenosine
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MOA Inhibitor
External Link
CID: 33113
TTD: D00ICA
 Compound Name PMID23489211C20 Investigative [11]
Synonyms
PCM126; GTPL8124; BDBM50428059
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2041.74 nM
External Link
CID: 71718651
TTD: D0X8BU
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [12]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
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MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [13]
MOA Inhibitor
External Link
TTD: DT8IL6
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [14]
Synonyms
INCMGA0012; Retifanlimab
    Click to Show/Hide
External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [15]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
    Click to Show/Hide
External Link
TTD: D0C9ET
 Compound Name 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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External Link
CID: 11167602
TTD: D09GDD
DrugBank: DB08896
 Compound Name Bevacizumab Approved [17]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
TTD: D04KBL
 Compound Name 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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External Link
TTD: D0CR8H
 Compound Name Bevacizumab + Erlotinib Phase 3 [18]
External Link
TTD: D09BKY
 Compound Name 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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External Link
CID: 24770514
TTD: D07NVI
DrugBank: DB12109
 Compound Name Bevacizumab Approved [15]
External Link
TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [19]
Synonyms
AlloStim (TN)
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External Link
TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [20]
External Link
TTD: DVX3H0
 Compound Name CV301 Phase 2 [21]
External Link
TTD: D9LT5G
 Compound Name 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
    Click to Show/Hide
External Link
CID: 9832447
TTD: D0Y8NZ
DrugBank: DB11894
 Compound Name LOR-2040 Phase 2 [23]
External Link
TTD: D0I7NG
 Compound Name RG7221 Phase 2 [24]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [25]
Synonyms
EZN-2208
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External Link
CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [26]
External Link
TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [27]
External Link
TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [28]
External Link
CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [24]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [29]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [17]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [30]
External Link
TTD: D0E2CQ
 Compound Name 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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External Link
CID: 4495
TTD: D0C0JT
DrugBank: DB04743
 Compound Name Saracatinib Phase 2 [32]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [33]
External Link
CID: 91865905
TTD: D05IAN
References
Ref 1 LINC01605, regulated by the EP300-SMYD2 complex, potentiates the binding between METTL3 and SPTBN2 in colorectal cancer. Cancer Cell Int. 2021 Sep 20;21(1):504. doi: 10.1186/s12935-021-02180-8.
Ref 2 m6A methylated EphA2 and VEGFA through IGF2BP2/3 regulation promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling. Cell Death Dis. 2022 May 21;13(5):483. doi: 10.1038/s41419-022-04950-2.
Ref 3 ClinicalTrials.gov (NCT02575261) CAR-T Cell Immunotherapy for EphA2 Positive Malignant Glioma Patients
Ref 4 MMAE Delivery Using the Bicycle Toxin Conjugate BT5528. Mol Cancer Ther. 2020 Jul;19(7):1385-1394. doi: 10.1158/1535-7163.MCT-19-1092. Epub 2020 May 12.
Ref 5 Clinical pipeline report, company report or official report of Daiichi Sankyo.
Ref 6 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: 1822).
Ref 7 Clinical and biological impact of EphA2 overexpression and angiogenesis in endometrial cancer. Cancer Biol Ther. 2010 Dec 15;10(12):1306-14. doi: 10.4161/cbt.10.12.13582. Epub 2010 Dec 15.
Ref 8 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8. doi: 10.1016/j.bmcl.2011.04.060. Epub 2011 Apr 22.
Ref 9 Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46. doi: 10.1021/jm9009444.
Ref 10 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 11 Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
Ref 12 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 13 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 14 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 15 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 16 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 17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 18 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 19 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 20 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 21 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 22 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 23 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 24 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 25 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 26 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 27 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 28 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 29 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 30 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 31 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 32 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 33 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.