m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03566
 [1], [2]
Histone modification H3K27ac EP300 LINC01605 Indirect Enhancement m6A modification IFN-gamma IFN-gamma METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) 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 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. 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
 CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-F10 Mouse melanoma Mus musculus CVCL_0159
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [3]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [4]
MOA Inhibitor
External Link
TTD: DT8IL6
Interferon gamma (IFN-gamma) 10 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Emapalumab Approved [5]
Synonyms
Emapalumab [INN]; Emapalumab [USAN:INN]; UNII-3S252O2Z4X; 3S252O2Z4X
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0UI7K
 Compound Name Fumaric acid Phase 3 [6]
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)
    Click to Show/Hide
MOA Binder
External Link
CID: 444972
TTD: D03GOO
DrugBank: DB01677
 Compound Name VIR-201 Phase 1/2 [7]
MOA Modulator
External Link
TTD: D0I5QV
 Compound Name AMG 811 Phase 1 [8]
MOA Modulator
External Link
TTD: D06FLP
 Compound Name CIGB-128 Phase 1 [9]
Synonyms
HeberPAG; IFN alpha2b + IFN gamma (injectable, skin cancer), CIGB
    Click to Show/Hide
MOA Modulator
External Link
TTD: D06NDP
 Compound Name TAK-603 Discontinued in Phase 2 [10]
MOA Modulator
External Link
CID: 153980
TTD: D0H6PX
 Compound Name Fontolizumab Discontinued in Phase 2 [11]
Synonyms
Fontolizumab (USAN/INN)
    Click to Show/Hide
External Link
TTD: D0N4ND
 Compound Name TG-1042 Discontinued in Phase 2 [12]
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
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0Z9MR
 Compound Name CRx-191 Discontinued in Phase 2 [13]
MOA Inhibitor
External Link
TTD: D0VA2I
 Compound Name VPM-4-001 Preclinical [14]
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
    Click to Show/Hide
External Link
TTD: D0WD6K
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [15]
Synonyms
INCMGA0012; Retifanlimab
    Click to Show/Hide
External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [16]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
    Click to Show/Hide
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]
    Click to Show/Hide
External Link
CID: 11167602
TTD: D09GDD
DrugBank: DB08896
 Compound Name Bevacizumab Approved [18]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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)
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
    Click to Show/Hide
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
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 m(6) A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy. EMBO J. 2020 Oct 15;39(20):e104514. doi: 10.15252/embj.2020104514. Epub 2020 Sep 23.
Ref 3 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 4 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 5 2018 FDA drug approvals. Nat Rev Drug Discov. 2019 Feb;18(2):85-89. doi: 10.1038/d41573-019-00014-x.
Ref 6 Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs. 2008 Sep;13(3):465-77. doi: 10.1517/14728214.13.3.465.
Ref 7 EP patent application no. 17782511, Nucleoside phosphonate conjugates as anti hiv agents.
Ref 8 Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-Gamma IgG1 monoclonal antibody, in patients with systemic lupus erythematosus. Pharm Res. 2015 Feb;32(2):640-53. doi: 10.1007/s11095-014-1492-2. Epub 2014 Sep 12.
Ref 9 Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial. BMC Pharmacol Toxicol. 2012 Dec 28;13:20. doi: 10.1186/2050-6511-13-20.
Ref 10 T helper 1 inhibitor TAK-603 inhibits IFN-gamma and IL-12 production with no effect on IL-18: an observation in sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis. 2004 Oct;21(3):204-11.
Ref 11 Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59. doi: 10.1517/14728214.12.1.49.
Ref 12 Drug evaluation: TG-1042, an adenovirus-mediated IFNgamma gene delivery for the intratumoral therapy of primary cutaneous lymphomas. Curr Opin Investig Drugs. 2007 Jun;8(6):493-8.
Ref 13 CombinatoRx Drug Candidate CRx-191 Demonstrates Positive Phase 2 Results In Psoriasis. CombinatoRx. 2008.
Ref 14 BioPartnering North America--Programs from Pharma in Europe and the Middle East. IDrugs. 2010 Mar;13(3):162-5.
Ref 15 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 16 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 17 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 18 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 19 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 20 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 21 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 22 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 23 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 24 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 25 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 26 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 27 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 28 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 29 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 30 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 31 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 32 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 33 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 34 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.