m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00460
 [1], [2], [3]
m6A modification CDK6 CDK6 HNRNPA2B1 : m6A sites Indirect Enhancement RNA modification MIR149 MIR149 METTL1 Methylation : modification sites
m6A Modification:
m6A Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
 Regulator Info 
m6A Target Cyclin-dependent kinase 6 (CDK6)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N7-methylguanosine (m7G)
Epigenetic Regulator Methyltransferase-like protein 1 (METTL1) WRITER View Details
Regulated Target MicroRNA 149 (MIR149) View Details
Crosstalk Relationship m7G  →  m6A Enhancement
Crosstalk Mechanism RNA modification indirectly impacts m6A modification through downstream signaling pathways
Crosstalk Summary METTL1 interacts with MicroRNA 149 (MIR149), increasing it's m7G level and promoting its physical interaction with Cyclin-dependent kinase 6 (CDK6), which was regulated by HNRNPA2B1-mediated m6A modification.
In-vitro Model
 PLA-801D Lung giant cell carcinoma Homo sapiens CVCL_7110
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cyclin-dependent kinase 6 (CDK6) 32 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Palbociclib Approved [4]
Synonyms
571190-30-2; PD0332991; PD-0332991; Ibrance; PD 0332991; UNII-G9ZF61LE7G; Palbociclib(PD0332991); 6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(piperazin-1-yl)pyridin-2-yl]amino]-8H-pyrido[2,3-d]pyrimidin-7-one; 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one; G9ZF61LE7G; PD 332991; 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE; LQQ; PD 332991, PD 0332991, PD0332991; 6-Acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-ylpyridin-2-ylamino)-8H-pyrido(2,3-d)pyrimidin-7-one; 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one; HMR-2934
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MOA Modulator
Activity IC50 = 15 nM
External Link
CID: 5330286
TTD: D00UZR
DrugBank: DB09073
 Compound Name Ribociclib Succinate Approved [5]
Synonyms
1374639-75-4; LEE011 succinate; LEE011 (succinate); UNII-BG7HLX2919; LEE011-BBA; Ribociclib succinate [USAN]; BG7HLX2919; Kisqali (TN); Ribociclib succinate (USAN); LEE-011 succinate; SCHEMBL2684999; EX-A1586; HY-15777B; 1374639-75-4 (succinate); AKOS030526460; CS-2277; ACN-040739
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MOA Modulator
External Link
CID: 57334219
TTD: D01HVT
 Compound Name LY2835219 Approved [6]
Synonyms
Abemaciclib; 1231929-97-7; Verzenio; LY-2835219; UNII-60UAB198HK; LY2835219 (free base);
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MOA Modulator
Activity IC50 = 1.9 nM
External Link
CID: 46220502
TTD: D05SBO
DrugBank: DB12001
 Compound Name Trilaciclib Approved [7]
Synonyms
G1T28; 1374743-00-6; Trilaciclib [USAN]; G1T28(Trilaciclib); GTPL9626; CHEMBL3894860; SCHEMBL10082028; BDBM253928; US9464092, T; HY-101467; CS-0021431; 2'-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro(cyclohexane-1,9'-pyrazino(1',2':1,5)pyrrolo(2,3-d)pyrimidin)-6'-one; Spiro(cyclohexane-1,9'(6'H)-pyrazino(1',2':1,5)pyrrolo(2,3-d)pyrimidin)-6'-one, 7',8'-dihydro-2'-((5-(4-methyl-1-piperazinyl)-2-pyridinyl)amino)-; 2-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]spiro[7,8-dihydropyra
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MOA Inhibitor
External Link
CID: 68029831
TTD: D0AP9E
DrugBank: DB15442
 Compound Name Apremilast Approved [8]
Synonyms
Apremilast (USAN); CC-10004; N-[2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methylsulfonyl-ethyl]-1,3-dioxo-isoindol-4-yl]acetamide
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MOA Inhibitor
External Link
CID: 11561674
TTD: D07ESC
DrugBank: DB05676
 Compound Name LEE011 Phase 3 [9]
Synonyms
Ribociclib; 1211441-98-3; LEE-011; Kisqali; Ribociclib(LEE011); UNII-TK8ERE8P56; LEE 011; 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; TK8ERE8P56; Ribociclib (LEE011); AK174906; 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo [2,3-d]pyrimidine-6-carboxylic acid dimethylamide; Ribociclib [USAN:INN]; LEE011A; Tube013
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MOA Modulator
Activity IC50 = 6 nM
External Link
CID: 44631912
TTD: D08MXP
DrugBank: DB11730
 Compound Name G1T38 Phase 2 [10]
Synonyms
YPJRHEKCFKOVRT-UHFFFAOYSA-N; SCHEMBL16036885; CHEMBL3904602; BDBM253941; US9464092, GG; 1628256-23-4
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MOA Inhibitor
External Link
CID: 86269224
TTD: D0WU1O
 Compound Name GLR2007 Phase 1/2 [11]
MOA Inhibitor
External Link
TTD: D4IS0G
 Compound Name FCN-437 Phase 1/2 [12]
MOA Inhibitor
External Link
TTD: D8ZV2Q
 Compound Name NUV-422 Phase 1/2 [13]
MOA Inhibitor
External Link
TTD: D70HZT
 Compound Name G1T28-1 Phase 1 [6]
MOA Modulator
External Link
TTD: D01XZG
 Compound Name RGT-419B Phase 1 [14]
MOA Inhibitor
External Link
TTD: DYH94Z
 Compound Name FN-1501 Phase 1 [15]
Synonyms
1429515-59-2; CHEMBL4077071; UNII-6MC966B505; TQR1001; BDBM50270304; NSC781143; 6MC966B505; NSC-781143; HY-111361; CS-0039834; 4((7HPyrrolo[2,3d]pyrimidin-4-yl)amino)N(4-((4-methylpiperazin-1-yl)methyl)phenyl)1Hpyrazole-3-carboxamide; 4-((7H-Pyrrolo (2,3-d)pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide; 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-5-carboxamide; 4a?(7Ha'Pyrrolo[2,3a'd]pyrimidin-4-yl)amino)a'Na?4-((4-methylpiperazin-1-yl)methyl)phenyl)a?Ha'pyrazole-3-carboxamide; N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide
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MOA Inhibitor
External Link
CID: 72195175
TTD: DKCU40
 Compound Name PMID25726713-Compound-49 Patented [16]
MOA Inhibitor
Activity IC50 < 50 nM
External Link
TTD: D07TVO
 Compound Name PMID25726713-Compound-51 Patented [16]
MOA Inhibitor
Activity IC50 < 50 nM
External Link
TTD: D0KH7Q
 Compound Name Isoquinoline 1,3-dione derivative 1 Patented [17]
Synonyms
PMID26161698-Compound-49
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MOA Inhibitor
Activity IC50 = 1 nM
External Link
TTD: D0W4MN
 Compound Name PMID25726713-Compound-48 Patented [16]
MOA Inhibitor
Activity IC50 < 50 nM
External Link
TTD: D0WJ3W
 Compound Name PMID25726713-Compound-47 Patented [16]
MOA Inhibitor
Activity IC50 < 50 nM
External Link
TTD: D0X5VI
 Compound Name PMID25726713-Compound-50 Patented [16]
MOA Inhibitor
Activity IC50 < 50 nM
External Link
TTD: D0Y8JF
 Compound Name Oxazolyl methylthiothiazole derivative 1 Patented [17]
Synonyms
PMID26161698-Compound-52
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MOA Inhibitor
Activity IC50 = 100 to 1000 nM
External Link
CID: 25195503
TTD: D0M5DX
 Compound Name INOC-005 Preclinical [18]
Synonyms
Capridine beta (prostate cancer), Prostagenics
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MOA Inhibitor
External Link
TTD: D07ZJC
 Compound Name CYC-103 Terminated [19]
Synonyms
Cyclin groove inhibitors, Cyclacel; CYC-103 (Pimetics series); CYC-103 cyclin groove inhibitors, Cyclacel; CYC-103 program, Cyclacel
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MOA Inhibitor
External Link
TTD: D0Y6HA
 Compound Name PD-0183812 Terminated [20]
Synonyms
PETCVZZPKYJZAU-UHFFFAOYSA-N; PD183812; AC1NS8PJ; CHEMBL139653; SCHEMBL5268115; BDBM6280; PD 0183812; N8 Pyrido[2,3-d]pyrimidin-7-one deriv 72; 8-{bicyclo[221]heptan-2-yl}-2-({4-[4-(3-hydroxypropyl)piperidin-1-yl]phenyl}amino)-7H,8H-pyrido[2,3-d]pyrimidin-7-one; 8-(3-bicyclo[221]heptanyl)-2-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]pyrido[2,3-d]pyrimidin-7-one; PD0183813
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MOA Inhibitor
External Link
CID: 5330258
TTD: D0Z0KD
 Compound Name Fascaplysin Investigative [20]
Synonyms
Pyrido[1,2-a:3,4-b']diindol-5-ium,12,13-dihydro-13-oxo-, chloride; GNF-PF-1458; ACMC-20bu3v; AC1L2JLY; AC1Q6JA3; SCHEMBL1728912; CHEMBL602937; GTPL5969; BDBM59087; CTK4A8872; CHEBI:93765; ZINC1616841; pyrido[1,2-a:3,4-b']diindol-5-ium, 12,13-dihydro-13-oxo-; HSCI1_000331; NCGC00346951-01; CJ-26101; BRD-K13287209-003-03-2; BRD-K13287209-311-02-1; BRD-K13287209-311-01-3; BRD-K13287209-003-02-4; BRD-K13287209-003-01-6
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MOA Inhibitor
Activity IC50 = 3400 nM
External Link
CID: 73292
TTD: D09OAH
 Compound Name Deschloroflavopiridol Investigative [20]
MOA Inhibitor
External Link
CID: 102397231
TTD: D0CI3C
 Compound Name RGB-286147 Investigative [21]
Synonyms
pyrazolopyrimidone analog, RGB-286147
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MOA Inhibitor
External Link
CID: 135473382
TTD: D0J4ON
 Compound Name Chrysin Investigative [22]
Synonyms
480-40-0; 5,7-Dihydroxyflavone; Chrysine; 5,7-Dihydroxy-2-phenyl-4H-chromen-4-one; Crysin; 5,7-dihydroxy-2-phenylchromen-4-one; 4H-1-Benzopyran-4-one, 5,7-dihydroxy-2-phenyl-; UNII-3CN01F5ZJ5; NSC-407436; FLAVONE, 5,7-DIHYDROXY-; EINECS 207-549-7; NSC407436; 5,7-Dihydroxy-2-phenyl-4H-1-benzopyran-4-one; CHEMBL117; NSC 407436; 5,7-Dihydroxy-2-phenyl-chromen-4-one; BRN 0233276; 3CN01F5ZJ5; CHEBI:75095; RTIXKCRFFJGDFG-UHFFFAOYSA-N; 5,7-Dihydroxy-2-phenyl-4H-benzo(b)pyran-4-one; MFCD00006834; Chrysin, 99+%; CAS-480-40-0
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MOA Inhibitor
Activity IC50 = 6000 nM
External Link
CID: 5281607
TTD: D01UYI
DrugBank: DB15581
 Compound Name 3,7,3',4'-TETRAHYDROXYFLAVONE Investigative [23]
Synonyms
Fisetin; 528-48-3; 2-(3,4-Dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one; 5-Desoxyquercetin; Fustel; Cotinin; Viset; 3,3',4',7-Tetrahydroxyflavone; Fisetholz; Superfustel; Fustet; Fietin; Junger fustik; Ventin sumach; Zante fustic; Young fustic; Superfustel K; Ungarisches gelbholz; CI Natural Brown 1; Young fustic crystals; Bois bleu de Honqrie; BOIS bleude honqrie; CI 75620; NSC 407010; NSC 656275; 5-Deoxyquercetin; 2-(3,4-Dihydroxyphenyl)-3,7-dihydroxy-4H-1-benzopyran-4-one; Natural Brown 1
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MOA Inhibitor
Activity IC50 = 850 nM
External Link
CID: 5281614
TTD: D0MF5Y
DrugBank: DB07795
 Compound Name APIGENIN Investigative [22]
Synonyms
520-36-5; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; Chamomile; Versulin; Spigenin; Apigenol; 4',5,7-Trihydroxyflavone; Apigenine; C.I. Natural Yellow 1; 5,7,4'-Trihydroxyflavone; Pelargidenon 1449; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4-benzopyrone; 2-(p-Hydroxyphenyl)-5,7-dihydroxychromone; UCCF 031; NSC 83244; UNII-7V515PI7F6; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one; CCRIS 3789; CHEBI:18388; CHEMBL28; EINECS 208-292-3; 4H-1-Benzopyran-4-one, 5,7-di
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MOA Inhibitor
Activity IC50 = 1700 nM
External Link
CID: 5280443
TTD: D00RIX
DrugBank: DB07352
 Compound Name 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Investigative [24]
Synonyms
1H-Pyrrole-2,5-dione, 3,4-bis(4-methoxyphenyl)-; 108774-82-9; ACMC-20mbs9; CHEMBL381099; CTK0G2626; DTXSID90449388
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MOA Inhibitor
External Link
CID: 10946795
TTD: D00NYT
 Compound Name 3,4-diphenyl-1H-pyrrole-2,5-dione Investigative [24]
Synonyms
2,3-diphenylmaleimide; 1H-Pyrrole-2,5-dione, 3,4-diphenyl-; 31295-36-0; AC1MBL6S; SCHEMBL114611; CHEMBL201949; CTK1B9880; 3,4-diphenylpyrrole-2,5-dione; DTXSID70372903; ZINC3847556
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MOA Inhibitor
External Link
CID: 2752461
TTD: D0C3WY
 Compound Name 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [24]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
CID: 11572699
TTD: D0EK0G
References
Ref 1 HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6. iScience. 2021 Oct 25;24(11):103345. doi: 10.1016/j.isci.2021.103345. eCollection 2021 Nov 19.
Ref 2 Overexpressed methyltransferase-like 1 (METTL1) increased chemosensitivity of colon cancer cells to cisplatin by regulating miR-149-3p/S100A4/p53 axis. Aging (Albany NY). 2019 Dec 20;11(24):12328-12344. doi: 10.18632/aging.102575. Epub 2019 Dec 20.
Ref 3 Knockdown of lncRNA DLEU1 inhibits the tumorigenesis of oral squamous cell carcinoma via regulation of miR?149?5p/CDK6 axis. Mol Med Rep. 2021 Jun;23(6):447. doi: 10.3892/mmr.2021.12086. Epub 2021 Apr 21.
Ref 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
Ref 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
Ref 8 Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
Ref 9 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. doi: 10.1158/1078-0432.CCR-13-1675. Epub 2013 Sep 17.
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
Ref 12 Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
Ref 13 ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
Ref 14 Clinical pipeline report, company report or official report of Regor Therapeutics
Ref 15 Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518. doi: 10.1021/acs.jmedchem.7b01261. Epub 2018 Feb 12.
Ref 16 Hedgehog inhibitors: a patent review (2013 - present). Expert Opin Ther Pat. 2015 May;25(5):549-65. doi: 10.1517/13543776.2015.1019864. Epub 2015 Mar 1.
Ref 17 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014). Expert Opin Ther Pat. 2015;25(9):953-70. doi: 10.1517/13543776.2015.1045414. Epub 2015 Jul 13.
Ref 18 What are next generation innovative therapeutic targets? Clues from genetic, structural, physicochemical, and systems profiles of successful targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15. doi: 10.1124/jpet.108.149955. Epub 2009 Apr 8.
Ref 19 WO patent application no. 2007,0898,78, Sutures and anti-scarring agents.
Ref 20 Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25. doi: 10.1016/s0165-6147(02)02071-0.
Ref 21 A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. doi: 10.1073/pnas.0708800104. Epub 2007 Dec 11.
Ref 22 Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. J Med Chem. 2005 Feb 10;48(3):737-43. doi: 10.1021/jm049353p.
Ref 23 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 24 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. doi: 10.1021/jm0580297.