m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03136
 [1]
Histone modification H3K18la EP300 YTHDC1 Direct Enhancement m6A modification NEAT1 NEAT1 YTHDC1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing protein 1 (YTHDC1) READER
 Regulator Info 
m6A Target Nuclear paraspeckle assembly transcript 1 (NEAT1)
 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 18 lactylation (H3K18la) View Details
Downstream Gene YTHDC1 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary Histone H3 lysine 18 lactylation (H3K18la) in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified Nuclear paraspeckle assembly transcript 1 (NEAT1). The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression.
Responsed Disease Liver cancer ICD-11: 2C12
 Disease Info 
In-vitro Model
 Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
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 [2]
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 [3]
MOA Inhibitor
External Link
TTD: DT8IL6
2C12: Liver cancer 49 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name 90Y-loaded resin microspheres Approved [4]
External Link
TTD: DGWE36
 Compound Name Thymalfasin Phase 2 [5]
Synonyms
Zadaxin; 62304-98-7; Thymosin alpha1; Thymosin alpha 1; Thymosin alpha1 (ox); Thymosin alpha1 (human); Thymalfasin [USAN:INN]; UNII-W0B22ISQ1C; Thymosin-alpha-1; 69440-99-9; Thymosin alpha1 (cattle); C129H215N33O55; W0B22ISQ1C; Zadaxin (TN); Thymalfasin alfa 1
    Click to Show/Hide
External Link
CID: 16130571
TTD: D0I5KX
 Compound Name Ferumoxides Approved [6]
Synonyms
AMI-25; 119683-68-0; Feridex; Feridex IV; Superparamagnetic iron oxide; UNII-G6N3J05W84; Ferumoxides [USAN:USP:BAN]; CCRIS 6722; HSDB 8072; AC1O5DID; G6N3J05W84; iron(2+); iron(3+); Iron oxide crystal is inverse spinel (X-ray data); Fe(II) and Fe(III) are present (Mossbauer Spectroscopy; Physical form is a colloidal particle of nonstoichiometric
    Click to Show/Hide
External Link
CID: 6432052
TTD: D08QAC
DrugBank: DB06215
 Compound Name DTI-015 Approved [7]
Synonyms
Carmustine; 154-93-8; 1,3-Bis(2-chloroethyl)-1-nitrosourea; BCNU; Carmustin; Nitrumon; Carmubris; Gliadel; BiCNU; Bi CNU; Carmustinum; Bischlorethylnitrosurea; Bischlorethylnitrosourea; Carmustina; Becenun; Becenum; Bischloroethyl nitrosourea; N,N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA; Bis(2-chloroethyl)nitrosourea; Urea, N,N'-bis(2-chloroethyl)-N-nitroso-; Gliadel Wafer; FDA 0345; Bischloroethylnitrosourea; SRI 1720; 1,3-Bis(2-chloroethyl)nitrosourea; BiCNU (TN); Carmustinum [INN-Latin]; Carmustina [INN-Spanish]; DTI 015; NCI-C04773; SK; Injectable carmustine, Direct Therapeutics
    Click to Show/Hide
External Link
CID: 2578
TTD: D01OXI
DrugBank: DB00262
 Compound Name Nofazinlimab Phase 3 [8]
Synonyms
CS1003; EQ176
    Click to Show/Hide
External Link
TTD: DX9GT7
 Compound Name PV-10 Phase 3 [9]
Synonyms
632-69-9; Rose bengal sodium; Rose bengal disodium salt; R105 sodium; Rose-bengal (131 I) natrium; Food Red No 105, sodium salt; EINECS 211-183-3; Food Red Color No 105, sodium salt; Sel disodique de rose bengale iodee (131 I); Rose bengale (131 I) sodique [INN-French]; Rosa bengala sodica (131 I) [INN-Spanish]; Roseum bengalense (131 I) natricum [INN-Latin]; 2,4,5,7-Tetraido(m,p,o',m')tetrachlorofluorescein, disodium salt; Fluorescein, 4,5,6,7-tetrachloro-2',4',5',7'-tetraiodo-, disodium salt; Disodium
    Click to Show/Hide
External Link
CID: 69438
TTD: D0L2VT
 Compound Name Brivanib Phase 3 [10]
Synonyms
649735-46-6; BMS-540215; Brivanib (BMS-540215); BMS 540215; UNII-DDU33B674I; Brivanib [USAN]; BMS540215; DDU33B674I; CHEMBL377300; (2R)-1-[4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]propanol; Brivanib (USAN); (2R)-1-[4-[(4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY]-5-METHYL-PYRROLO[2,1-F][1,2,4]TRIAZIN-6-YL]OXYPROPAN-2-OL; (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-ol
    Click to Show/Hide
External Link
CID: 11234052
TTD: D0HS5V
DrugBank: DB11958
 Compound Name JX-594 Phase 3 [11]
Synonyms
Pexastimogene devacirepvec
    Click to Show/Hide
External Link
TTD: D0HB0V
 Compound Name ABH001 Phase 3 [12]
External Link
TTD: D05LPP
 Compound Name MTC-DOX Phase 2/3 [13]
Synonyms
MTC-doxorubicin
    Click to Show/Hide
External Link
TTD: D0W9AI
 Compound Name KD018 Phase 2 [14]
External Link
TTD: D0NB9T
 Compound Name Doxorubicin-eluting beads Phase 2 [15]
Synonyms
DC Bead (TN)
    Click to Show/Hide
External Link
TTD: D0M5CD
 Compound Name 32-P BioSilicon Phase 2 [16]
Synonyms
BrachySil
    Click to Show/Hide
External Link
TTD: D0M1YS
 Compound Name Cixutumumab Phase 2 [17]
Synonyms
LY3012217
    Click to Show/Hide
External Link
TTD: D0E5DP
 Compound Name [131I]-Metuximab Phase 2 [18]
External Link
TTD: D0E5BW
 Compound Name Darinaparsin Phase 2 [19]
Synonyms
ZIO-101
    Click to Show/Hide
External Link
CID: 11683005
TTD: D03ZME
DrugBank: DB06179
 Compound Name Tigatuzumab Phase 2 [20]
External Link
TTD: D03LTO
 Compound Name CMC-001 Phase 2 [21]
Synonyms
Manganese-based MRI contrast agent (liver tumor imaging), CMC Contrast
    Click to Show/Hide
External Link
TTD: D00WMJ
 Compound Name OBP-301 Phase 1/2 [22]
External Link
TTD: D0D8ZK
 Compound Name MBO7133 Phase 1/2 [23]
External Link
TTD: D0C3MW
 Compound Name INCB62079 Phase 1/2 [9]
External Link
TTD: D0BE8H
 Compound Name NV-1020 Phase 1/2 [24]
External Link
TTD: D0B6EA
 Compound Name DCVax-Liver Phase 1/2 [25]
Synonyms
Dendritic cell-based immunotherapy (liver cancer), Northwest Biotherapeutics
    Click to Show/Hide
External Link
TTD: D00ESH
 Compound Name SRF388 Phase 1 [26]
External Link
TTD: DLY89F
 Compound Name ET140202 Phase 1 [27]
External Link
TTD: D4K2OF
 Compound Name ADP-A2AFP Phase 1 [28]
External Link
TTD: D31ORV
 Compound Name SM04755 Phase 1 [29]
External Link
TTD: D0P5XM
 Compound Name Anti-CEA CAR-T therapy Phase 1 [9]
External Link
TTD: D0OP1L
 Compound Name PI-166 Phase 1 [30]
External Link
TTD: D0J2YR
 Compound Name CRS-100 Phase 1 [31]
External Link
TTD: D0B4DL
 Compound Name Autologous ET1402L1-CART cells Phase 1 [32]
External Link
TTD: D09TGO
 Compound Name Anti-CD133-CAR vector-transduced T cells Phase 1 [33]
External Link
TTD: D09HRH
 Compound Name MRX34 Phase 1 [34]
External Link
TTD: D08SJY
 Compound Name ALN-VSP Phase 1 [35]
External Link
TTD: D08JMI
 Compound Name EPCAM-targeted CAR-T cells Clinical trial [36]
External Link
TTD: D0T8DD
 Compound Name ADI Discontinued in Phase 3 [37]
Synonyms
Arginine deiminase
    Click to Show/Hide
External Link
CID: 46906074
TTD: D0O4EV
 Compound Name GN-1140 Discontinued in Phase 2 [38]
External Link
TTD: D0V4CL
 Compound Name OGT-719 Discontinued in Phase 2 [39]
Synonyms
OGS-719
    Click to Show/Hide
External Link
CID: 9838997
TTD: D0C2CH
 Compound Name AFP-Scan Discontinued in Phase 2 [40]
External Link
TTD: D08CCC
 Compound Name SR1078 Preclinical [41]
Synonyms
1246525-60-9; SR 1078; SR-1078; N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-(trifluoromethyl)benzamide; CHEMBL3094387; N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-4-(trifluoromethyl)benzamide; N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide; SCHEMBL4880524; C17H10F9NO2; DTXSID30591895; BCP09203; EX-A2215; 4063AH; BDBM50444350; s5775; ZINC98052696; AKOS024458390; CS-1045; NCGC00379222-02; AK547149; AS-55921; HY-14422; W-5797; SR-03000001078; SR-03000001078-1; SR-03000001078-2
    Click to Show/Hide
External Link
CID: 17980288
TTD: D9D6QN
 Compound Name Occlusin Preclinical [42]
Synonyms
Occlusin 50 Injection; Occlusin 500 injection
    Click to Show/Hide
External Link
TTD: D00INM
 Compound Name HRC-201 Terminated [43]
Synonyms
Hemoglobin-imaging conjugate (HepSelect), Hemosol
    Click to Show/Hide
External Link
TTD: D09ZCH
 Compound Name 1,2,3,4,5,6-hexabromocyclohexane Investigative [44]
Synonyms
1837-91-8; Benzene hexabromide; Cyclohexane, 1,2,3,4,5,6-hexabromo-; Hexabromocyclohexane; JAK2 Inhibitor II; ACMC-1BQJT; SCHEMBL459442; trans-alpha-Benzene hexabromide; CHEMBL444236; DTXSID4052687; CHEBI:93940; NSC7908; HMS3268H22; HMS3413C10; HMS3677C10; NSC-7908; ZINC1586309; ANW-23174; MFCD00059127; s5902; Cyclohexane,2,3,4,5,6-hexabromo-; AKOS015836040; 1,2,3,4,5,6-Hexabromo-cyclohexane; 1,2,3,4,5,6-Hexabromocyclohexane #; NCGC00092358-01; NCGC00092358-02; 1,2,3,4,5,6-hexakis(bromanyl)cyclohexane; A4510; FT-0633875; JAK2 Inhibitor II - CAS 1837-91-8; 1,2,3,4,5,6-Hexabromocyclohexane;NSC7908; A812818; 1,2,3,4,5,6-Hexabrom-cyclohexan (I(2)-Form); J-011778; 1,2,3,4,5,6-Hexabromocyclohexane, >=98% (HPLC); BRD-K06817181-001-01-5; Q27165694
    Click to Show/Hide
External Link
CID: 74603
TTD: DLW69V
 Compound Name STP-322 Investigative [45]
Synonyms
Multi-targeted siRNA therapeutic cocktail (nanoparticle, liver tumor), Sirnaomics
    Click to Show/Hide
External Link
TTD: D0R8KF
 Compound Name AMB-8LK Investigative [45]
Synonyms
Cancer therapy (monoclonal antibody), MAT Biopharma; Y90 anti-ferritin monoclonal antibody (cancer), MAT Biopharma; Yttrium-90 anti-ferritin mAb (cancer), MAT Biopharma; Yttrium-90 anti-ferritin mAb (Hodgkin's disease/pancreatic/liver cancer), MAT Biopharma; 90Y-AMB8LK mAb (cancer), MAT Biopharma; 90Y-AMB8LK monoclonal antibody (cancer), MAT Biopharma; 90Y-labelled anti-ferritin monoclonal antibody (cancer), MAT Biopharma
    Click to Show/Hide
External Link
TTD: D0P2MD
 Compound Name MiR-34a mimics Investigative [45]
Synonyms
MiR-34a mimics (liver cancer)
    Click to Show/Hide
External Link
TTD: D0M9TD
 Compound Name P53 fusion protein Investigative [45]
Synonyms
P53 fusion protein (pancreatic/liver cancer)
    Click to Show/Hide
External Link
TTD: D06WLG
 Compound Name OP-05 Investigative [45]
Synonyms
OP-05 program (prodrug, liver tumor); OP-05 program (prodrug, liver tumor), Onco-Pharmakon
    Click to Show/Hide
External Link
TTD: D02OIP
 Compound Name GR-DD1 Investigative [45]
Synonyms
Cytotoxin (hepatic metastasis), ERYtech
    Click to Show/Hide
External Link
TTD: D00QFV
References
Ref 1 Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling. Cancer Lett. 2024 Dec 24;611:217426. doi: 10.1016/j.canlet.2024.217426. Online ahead of print.
Ref 2 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 3 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services.
Ref 5 ClinicalTrials.gov (NCT01031966) A Pilot Study to Evaluate ZADAXIN's (Thymalfasin) Ability to Enhance Immune Response to the H1N1sw Influenza Vaccine. U.S. National Institutes of Health.
Ref 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 7 Carmustine-induced toxicity, DNA crosslinking and O6-methylguanine-DNA methyltransferase activity in two human lung cancer cell lines. Eur J Cancer. 1991;27(12):1658-62.
Ref 8 ClinicalTrials.gov (NCT04194775) A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC). U.S.National Institutes of Health.
Ref 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 10 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: 5671).
Ref 11 ClinicalTrials.gov (NCT02017678) Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin. U.S. National Institutes of Health.
Ref 12 ClinicalTrials.gov (NCT01749306) A Study of the Efficacy and Safety of ABH001 in the Treatment of Patients With Epidermolysis Bullosa Who Have Wounds That Are Not Healing. U.S. National Institutes ofHealth.
Ref 13 ClinicalTrials.gov (NCT00034333) Safety and Efficacy of Doxorubicin Adsorbed to Magnetic Beads Vs. IV Doxorubicin in Treating Liver Cancer. U.S. National Institutes of Health.
Ref 14 ClinicalTrials.gov (NCT00730158) A Phase II Multicenter, Randomized, Placebo Controlled, Double Blinded Clinical Study of KD018 as a Modulator of Irinotecan Chemotherapy in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 15 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026037)
Ref 16 PRODUCTS: BrachySil. Psivida corp
Ref 17 ClinicalTrials.gov (NCT01232452) A Study in Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 18 ClinicalTrials.gov (NCT00819650) A Trial of Licartin for Preventing Tumor Recurrence After Liver Resection. U.S. National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT00421213) Phase II Study of ZIO-101 in Advanced Blood and Bone Marrow Cancers. U.S. National Institutes of Health.
Ref 20 ClinicalTrials.gov (NCT01307891) Abraxane With or Without Tigatuzumab in Patients With Metastatic, Triple Negative Breast Cancer. U.S. National Institutes of Health.
Ref 21 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021589)
Ref 22 ClinicalTrials.gov (NCT02293850) Phase I/II Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma. U.S. National Institutes of Health.
Ref 23 Clinical pipeline report, company report or official report of Metabasis Therapeutics (2006).
Ref 24 ClinicalTrials.gov (NCT00149396) Safety and Efficacy of a Genetically Engineered Herpes Simplex Virus NV1020 to Treat Colorectal Cancer Metastatic to Liver. U.S. National Institutes of Health.
Ref 25 ClinicalTrials.gov (NCT01882946) Safety and Efficacy Study of DCVax-Direct in Solid Tumors. U.S. National Institutes of Health.
Ref 26 ClinicalTrials.gov (NCT04374877) Study of SRF388 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 27 ClinicalTrials.gov (NCT03965546) Clinical Study of ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Advanced Liver Cancer. U.S.National Institutes of Health.
Ref 28 ClinicalTrials.gov (NCT03132792) A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFP????T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC) or Other AFP Expressing Tumor Types. U.S.National Institutes of Health.
Ref 29 ClinicalTrials.gov (NCT02191761) Safety and Pharmacokinetics of SM04755 in Subjects With Advanced Colorectal, Gastric, Hepatic, or Pancreatic Cancer. U.S. National Institutes of Health.
Ref 30 Clinical pipeline report, company report or official report of Progen.
Ref 31 ClinicalTrials.gov (NCT00327652) Study of Safety and Tolerability of Intravenous CRS-100 in Adults With Carcinoma and Liver Metastases. U.S. National Institutes of Health.
Ref 32 ClinicalTrials.gov (NCT03349255) Clinical Study of ET1402L1-CAR T Cells in AFP Expressing Hepatocellular Carcinoma
Ref 33 ClinicalTrials.gov (NCT02541370) Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133
Ref 34 ClinicalTrials.gov (NCT01829971) A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection. U.S. National Institutes of Health.
Ref 35 Clinical pipeline report, company report or official report of Alnylam Pharmaceuticals, Inc (2011).
Ref 36 ClinicalTrials.gov (NCT02729493) Study Evaluating the Efficacy and Safety With CAR-T for Liver Cancer
Ref 37 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003116)
Ref 38 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015394)
Ref 39 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009854)
Ref 40 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008092)
Ref 41 Circadian rhythm as a therapeutic target. Nat Rev Drug Discov. 2021 Apr;20(4):287-307.
Ref 42 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018427)
Ref 43 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020214)
Ref 44 Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J Nutr. 2007 Nov;137(11):2366-70.
Ref 45 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.