m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03625
 [1], [2]
Histone modification H3K4me3 SMYD2 LINC01605 Indirect Enhancement m6A modification REG1A REG1A METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Lithostathine-1-alpha (REG1A)
 Targert Gene 
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. the malignant behaviors governed by Lithostathine-1-alpha (REG1A) could be effectively abolished by silencing of Wnt/beta-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1alpha expression was mediated by METTL3 in an m6A-dependent manner.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model
 NCM460 Normal Homo sapiens CVCL_0460
FHC Normal Homo sapiens CVCL_3688
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
In-vivo Model For in vivo lung metastases model, a total of 2 × 106 CRC cells with REG1alpha-overexpression or REG1alpha-knockdown were injected into nude mice via lateral tail vein. Six weeks after injection, the mice were sacrificed and the lung tissues were collected.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
N-lysine methyltransferase SMYD2 (SMYD2) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name AZ505 Preclinical [3]
Synonyms
AZ 505; AZ-505
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MOA Inhibitor
Activity IC50 = 120 nM
External Link
CID: 24961094
TTD: D06ONB
 Compound Name LLY-507 Preclinical [4]
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
CID: 91623361
TTD: D0X3RK
 Compound Name EPZ032597 Preclinical [5]
MOA Inhibitor
External Link
TTD: D35SKV
 Compound Name EPZ033294 Preclinical [5]
MOA Inhibitor
External Link
TTD: DDC63W
 Compound Name A-893 Preclinical [6]
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
CID: 91757965
TTD: DELC48
 Compound Name BAY 598 Preclinical [7]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 117072551
TTD: DT6P8M
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [8]
Synonyms
INCMGA0012; Retifanlimab
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External Link
TTD: D0PG5O
 Compound Name Aflibercept Approved [9]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
TTD: D0C9ET
 Compound Name Regorafenib Approved [10]
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 [11]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
TTD: D04KBL
 Compound Name SYM-004 Phase 3 [11]
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 [12]
External Link
TTD: D09BKY
 Compound Name CPI-613 Phase 3 [11]
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 [9]
External Link
TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [13]
Synonyms
AlloStim (TN)
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External Link
TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [14]
External Link
TTD: DVX3H0
 Compound Name CV301 Phase 2 [15]
External Link
TTD: D9LT5G
 Compound Name Efatutazone Phase 2 [16]
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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External Link
CID: 9832447
TTD: D0Y8NZ
DrugBank: DB11894
 Compound Name LOR-2040 Phase 2 [17]
External Link
TTD: D0I7NG
 Compound Name RG7221 Phase 2 [18]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [19]
Synonyms
EZN-2208
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External Link
CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [20]
External Link
TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [21]
External Link
TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [22]
External Link
CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [18]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [23]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [11]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [24]
External Link
TTD: D0E2CQ
 Compound Name Nimesulide Terminated [25]
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 [26]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [27]
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 N(6)-methyladenosine modification of REG1alpha facilitates colorectal cancer progression via beta-catenin/MYC/LDHA axis mediated glycolytic reprogramming. Cell Death Dis. 2023 Aug 25;14(8):557. doi: 10.1038/s41419-023-06067-6.
Ref 3 Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73.
Ref 4 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: 2714).
Ref 5 Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286. doi: 10.1038/s41573-020-00108-x. Epub 2021 Jan 19.
Ref 6 Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. ACS Med Chem Lett. 2015 Apr 29;6(6):695-700.
Ref 7 Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2. J Med Chem. 2016 May 26;59(10):4578-600.
Ref 8 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 9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 5891).
Ref 11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 12 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 14 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 15 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 16 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 17 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 18 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 19 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 20 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 21 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 22 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 23 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 24 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 25 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 26 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 27 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.