Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05566
[1]
m6A modification hsa_circ_0000677 hsa_circ_0000677 METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA circ_0000677 ABCC1  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target hsa_circ_0000677
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa_circ_0000677 (Circ_ABCC1) circRNA View Details
Regulated Target ATP binding cassette subfamily C member 1 (ABCC1 blood group) (ABCC1) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary hsa_circ_0000677 and its downstream target ATP binding cassette subfamily C member 1 (ABCC1 blood group) (ABCC1) were upregulated in CRC cells, induced by the METTL3-mediated m6 A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC.
Responsed Disease Colorectal cancer ICD-11: 2B91
Cell Process Cell proliferation
In-vitro Model
NCM460 Normal Homo sapiens CVCL_0460
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
Caco-2 Colon adenocarcinoma Homo sapiens CVCL_0025
In-vivo Model For the tumor xenograft, mice were randomly divided into three groups with four mice for each group. Then, 1 × 106 cells after indicated treatment were harvested and resuspended in 50 ul of PBS. Then the cells were subcutaneously injected into the right front flank of each mouse.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
ATP binding cassette subfamily C member 1 (ABCC1 blood group) (ABCC1) 7 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Sulfinpyrazone Approved [2]
Synonyms
Anturan; Anturane; Anturanil; Anturano; Anturen; Anturidin; Diphenylpyrazone; Enturan; Enturen; Novopyrazone; Sulfinpirazona; Sulfinpyrazine; Sulfinpyrazon; Sulfinpyrazonum; Sulfoxyphenylpyrazolidin; Sulfoxyphenylpyrazolidine; Sulphinpyrazone; Apo Sulfinpyrazone; Apotex Brand of Sulfinpyrazone; Novartis Brand of Sulfinpyrazone; Nu Pharm Brand of Sulfinpyrazone; Nu Sulfinpyrazone; G 28315; Anturane (TN); Apo-Sulfinpyrazone; G 28,315; Nu-Pharm Brand of Sulfinpyrazone; Nu-Sulfinpyrazone; Sulfinpirazona [INN-Spanish]; Sulfinpyrazone (SPZ); Sulfinpyrazonum [INN-Latin]; USAF GE-13; Sulfinpyrazone [USAN:INN:JAN]; Sulfinpyrazone (JP15/USP/INN); (+/-)-SULFINPYRAZONE; 1,2-Diphenyl-3,5-dioxo-4-(2'-phenyl-sulfinyl-aethyl)-pyrazolidin; 1,2-Diphenyl-3,5-dioxo-4-(2'-phenyl-sulfinyl-aethyl)-pyrazolidin [German]; 1,2-Diphenyl-3,5-dioxo-4-(2-phenylsulfinylethyl) pyrazolidine; 1,2-Diphenyl-3,5-dioxo-4-(2-phenylsulfinylethyl)pyrazolidine; 1,2-Diphenyl-4-(2'-phenylsulfinethyl)-3,5-pyrazolidinedione; 1,2-Diphenyl-4-(2-(phenylsulfinyl)ethyl)-3,5-pyrazolidinedione; 1,2-Diphenyl-4-(phenylsulfinylethyl)-3,5-pyrazolidinedione; 1,2-Diphenyl-4-[2-(phenylsulfinyl)ethyl-3,5-pyrazolidinedione; 1,2-diphenyl-4-[2-(phenylsulfinyl)ethyl]pyrazolidine-3,5-dione; 4-(2-Benzenesulfinylethyl)-1,2-diphenylpyrazolidine-3,5-dione; 4-(Phenylsulfoxyethyl)-1,2-diphenyl-3,5-pyrazolidinedione; 4-[2-(benzenesulfinyl)ethyl]-1,2-diphenylpyrazolidine-3,5-dione
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MOA Modulator
External Link
 Compound Name Benzbromarone Approved [3]
Synonyms
Acifugan; Azubromaron; Benzbromaron; Benzbromaronratiopharm; Benzbromaronum; Benzobromarona; Besuric; Desuric; Exurate; Harolan; Hipurik; Minuric; Narcaricin; Normurat; Uricovac; Urinorm; Uroleap; Aliud Brand of Benzbromarone; Benzbromaron AL; Benzbromaron ratiopharm; Benzbromarone Aliud Brand; Benzbromarone Heumann Brand; Benzbromarone Sanfer Brand; Benzbromarone ratiopharm Brand; Heumann Brand of Benzbromarone; Ratiopharm Brand of Benzbromarone; Sanfer Brand of Benzbromarone; Sanofi Winthrop Brand of Benzbromarone; L 2214; L2214; MJ 10061; NCI85433; AL, Benzbromaron; Benzbromaron-ratiopharm; Benzbromaronum [INN-Latin]; Benzobromarona [INN-Spanish]; L 2214-Labaz; L-2214; Uroleap (TN); Benzbromarone [USAN:INN:BAN]; Methanone, (3; Benzbromarone (JP15/USAN/INN); KETONE, 3,5-DIBROMO-4-HYDROXYPHENYL 2-ETHYL-3-BENZOFURANYL; (2-Ethyl-3-benzofuranyl)-(3,5-dibrom-4-hydroxyphenyl)keton; (3,5-Dibromo-4-hydroxyphenyl)(2-ethyl-1-benzofuran-3-yl)methanone; (3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone; 2-Ethyl-3-(3,5-dibrom-4-hydroxybenzoyl)benzofuran; 3, 5-Dibromo-4-hydroxyphenyl-2-ethyl-3-benzofuranyl ketone; 3,5-Dibromo-4-hydroxyphenyl-2-ethyl-3-benzofuranyl ketone; 3-(3,5-Dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran; 3-[3,5-DIBROMO-4-HYDROXYBENZOYL]-2-ETHYLBENZOFURAN
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MOA Stimulator
Activity Ki = 190 nM
External Link
 Compound Name Pyrrolopyrimidine Investigative [4]
MOA Inhibitor
External Link
 Compound Name XR-9456 Investigative [5]
Synonyms
CHEMBL346292; SCHEMBL7170174; BDBM50375810
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MOA Inhibitor
External Link
 Compound Name XR-9504 Investigative [5]
Synonyms
CHEMBL258896; SCHEMBL7168501
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MOA Inhibitor
External Link
 Compound Name XR-9544 Investigative [5]
Synonyms
CHEMBL444075; SCHEMBL14290581; BDBM50375811
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MOA Inhibitor
External Link
 Compound Name XR-9577 Investigative [5]
Synonyms
CHEMBL428402
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MOA Inhibitor
External Link
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [6]
Synonyms
INCMGA0012; Retifanlimab
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External Link
 Compound Name Aflibercept Approved [7]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
 Compound Name Regorafenib Approved [8]
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
 Compound Name Bevacizumab Approved [9]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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External Link
 Compound Name SYM-004 Phase 3 [9]
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
 Compound Name Bevacizumab + Erlotinib Phase 3 [10]
External Link
 Compound Name CPI-613 Phase 3 [9]
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
 Compound Name Bevacizumab Approved [7]
External Link
 Compound Name AlloStim Phase 2/3 [11]
Synonyms
AlloStim (TN)
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External Link
 Compound Name Sibrotuzumab Phase 2 [12]
External Link
 Compound Name CV301 Phase 2 [13]
External Link
 Compound Name Efatutazone Phase 2 [14]
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
 Compound Name LOR-2040 Phase 2 [15]
External Link
 Compound Name RG7221 Phase 2 [16]
External Link
 Compound Name PEG-SN38 Phase 2 [17]
Synonyms
EZN-2208
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External Link
 Compound Name MEGF0444A Phase 2 [18]
External Link
 Compound Name Encapsulated cell therapy Phase 1/2 [19]
External Link
 Compound Name AB928 Phase 1/2 [20]
External Link
 Compound Name MGD007 Phase 1 [16]
External Link
 Compound Name BNC-101 Phase 1 [21]
External Link
 Compound Name Navicixizumab Phase 1 [9]
External Link
 Compound Name RG7160 Discontinued in Phase 2 [22]
External Link
 Compound Name Nimesulide Terminated [23]
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
 Compound Name Saracatinib Phase 2 [24]
External Link
 Compound Name G3139 + Irinotecan Investigative [25]
External Link
References
Ref 1 SUMOylation of methyltransferase-like 3 facilitates colorectal cancer progression by promoting circ_0000677 in an m(6) A-dependent manner. J Gastroenterol Hepatol. 2022 Apr;37(4):700-713. doi: 10.1111/jgh.15775. Epub 2022 Feb 14.
Ref 2 Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos. 2008 Apr;36(4):631-40.
Ref 3 Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transport by diclofenac and benzbromarone. Drug Metab Dispos. 2009 Jan;37(1):129-36. doi: 10.1124/dmd.108.023200. Epub 2008 Oct 9.
Ref 4 Topological model for the prediction of MRP1 inhibitory activity of pyrrolopyrimidines and templates derived from pyrrolopyrimidine. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4967-72.
Ref 5 Functional assay and structure-activity relationships of new third-generation P-glycoprotein inhibitors. Bioorg Med Chem. 2008 Mar 1;16(5):2448-62. doi: 10.1016/j.bmc.2007.11.057. Epub 2007 Nov 28.
Ref 6 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 7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 8 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 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 10 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 12 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 13 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 14 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 15 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 16 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 17 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 18 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 19 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 20 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 21 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 22 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 23 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 24 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 25 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.