m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03327
 [1], [2]
Histone modification H3K4me3 KDM5A hsa-miR-495 Indirect Enhancement m6A modification THBS1 THBS1 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Thrombospondin-1 (THBS1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 5A (KDM5A) ERASER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene hsa-miR-495 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary KDM5A, as a Histone H3 lysine 4 trimethylation (H3K4me3) demethylase, bound to the hsa-miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA.
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response RNA degradation hsa03018
Cell Process Cell proliferation
In-vitro Model
 DU145 Prostate carcinoma Homo sapiens CVCL_0105
HNC PC3 Retromolar trigone squamous cell carcinoma Homo sapiens CVCL_C8XA
In-vivo Model Stably transfected shMETTL14 and shNC DU145 cells (5× 106 cells) suspended in a mixture of 100uL PBS were subcutaneously injected into the right flank of male nude BALB/C mice (6-8 weeks old) to induce tumor formation.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Lysine-specific demethylase 5A (KDM5A) 21 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name 6EP Patented [3]
Synonyms
2-{5-[(4-Chloro-2-Methylphenyl)methoxy]-1h-Pyrazol-1-Yl}pyridine-4-Carboxylic Acid; 1613410-75-5; CHEMBL3786952; SCHEMBL15778339; BDBM191600; NCGC00390881-02; QC3611,QC-3611,QC 3611; 2-(5-((4-chloro-2-methylbenzyl)oxy)-1Hpyrazol-1-yl)isonicotinic acid (N19)
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MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 74766595
TTD: D00SUC
 Compound Name BDBM50158803 Patented [4]
Synonyms
CHEMBL3787438; SCHEMBL15792889
    Click to Show/Hide
MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 90216982
TTD: D01WHH
 Compound Name US10022354, Example 151 Patented [5]
Synonyms
SCHEMBL19513974; CHEMBL4060968; BDBM281211
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 0.065 nM
External Link
CID: 132054530
TTD: D03POM
 Compound Name US9714230, 12 Patented [3]
Synonyms
SCHEMBL15778399; LKBZHRSAENXIOI-UHFFFAOYSA-N; BDBM263942; 2-(5-p-tolyl-1H-pyrazol-1- yl)isonicotinic acid; 2-(5-p-tolyl-1H-pyrazol-1-yl)isonicotinic acid
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MOA Inhibitor
Activity IC50 = 550 nM
External Link
CID: 76901247
TTD: D03TKM
 Compound Name BDBM50158791 Patented [6]
Synonyms
CHEMBL3786596; SCHEMBL15818867; SCHEMBL19646964
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MOA Inhibitor
Activity IC50 = 550 nM
External Link
CID: 77106319
TTD: D05CCY
 Compound Name US10040779, Example 4 Patented [7]
Synonyms
SCHEMBL15792083; BDBM277707; 3-[(5-chloro-1-methyl-1H-indazol-3-yl)amino]pyridine-4-carboxylic acid
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MOA Inhibitor
Activity IC50 < 0.1nM
External Link
CID: 75202257
TTD: D06TKT
 Compound Name US9611221, Example 9 Patented [8]
Synonyms
3-[(biphenyl-4-ylmethyl)amino]pyridine-4-carboxylic acid; SCHEMBL15286753; RNBCOBWQQCESLL-UHFFFAOYSA-N; BDBM314105
    Click to Show/Hide
MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 71766727
TTD: D09CWB
 Compound Name US9714230, 46 Patented [9]
Synonyms
SCHEMBL15778753; MITOFELVTHNBGA-UHFFFAOYSA-N; BDBM263981; 2-(5-(4-bromophenyl)-1H-pyrazol- 1-yl)isonicotinic acid; 2-[5-(4-bromophenyl)-1H-pyrazol-1-yl]pyridine-4-carboxylic acid
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MOA Inhibitor
Activity IC50 < 10nM
External Link
CID: 86725517
TTD: D0F3TL
 Compound Name BDBM50158794 Patented [7]
Synonyms
CHEMBL3785470; SCHEMBL15792416
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MOA Inhibitor
Activity IC50 < 0.1nM
External Link
CID: 76282772
TTD: D0G8QR
 Compound Name BDBM50158703 Patented [3]
Synonyms
CHEMBL3785832; SCHEMBL15777940
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MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 90204862
TTD: D0GH8J
 Compound Name AKOS020330656 Patented [10]
Synonyms
CHEMBL3774545; SCHEMBL15820618; RFUZGPWCXINBNW-UHFFFAOYSA-N; BDBM50153334; ZINC123452149; 3-{[(5-methylthiophen-2-yl)methyl]amino}pyridine-4-carboxylic acid
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MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 77106317
TTD: D0HT9Q
 Compound Name BDBM50158755 Patented [11]
Synonyms
CHEMBL3786579; SCHEMBL15778210
    Click to Show/Hide
MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 90205053
TTD: D0K4LW
 Compound Name US10174026, Example 99 Patented [12]
Synonyms
SCHEMBL16157351; BDBM320432; 2-(pyrrolidin-1-ylcarbonyl)-1H- pyrrolo[3,2-b]pyridine-7- carboxylic acid
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MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 85469291
TTD: D0N9JZ
 Compound Name AKOS020330481 Patented [8]
Synonyms
3-[(4-methoxybenzyl)amino]pyridine-4-carboxylic acid; SCHEMBL4855920; US9611221, Example 7; XKZFNTZMCLZYHZ-UHFFFAOYSA-N; BDBM314103; 3[(4-methoxybenzyl)amino]pyridine-4-carboxylic acid
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MOA Inhibitor
Activity IC50 = 550 nM
External Link
CID: 59699608
TTD: D0NG8M
 Compound Name US10022354, Example 5 Patented [5]
Synonyms
SCHEMBL17682496; CHEMBL4062756; BDBM281065
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 7.4 nM
External Link
CID: 121279569
TTD: D0NM3B
 Compound Name NCGC00381656-01 Patented [13]
Synonyms
CHEMBL4100530; SCHEMBL16157407; BDBM320423; US10174026, Example 88; 2-[(2-chlorophenyl)-propoxy- methyl]-1H-pyrrolo[3,2-b]- pyridine-7-carboxylic acid
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MOA Inhibitor
Activity IC50 < 100nM
External Link
CID: 117637389
TTD: D0PQ5P
 Compound Name US10174026, Example 2 Patented [12]
Synonyms
SCHEMBL16149258; FEZIKLVLFANZBD-UHFFFAOYSA-N; BDBM320362; 2-phenyl-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid; 2-phenyl-1H-pyrrolo[3,2-b] pyridine-7-carboxylic acid
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 550 nM
External Link
CID: 86280871
TTD: D0R2GT
 Compound Name US10022354, Example 152 Patented [5]
Synonyms
CHEMBL4059597; SCHEMBL17682668; BDBM281212
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MOA Inhibitor
Activity IC50 = 0.083 nM
External Link
CID: 121279737
TTD: D0T8YT
 Compound Name US10040779, Example 1 Patented [7]
Synonyms
SCHEMBL15792304; BDBM277704; 3-[(1-methyl-1H-indazol-3-yl)amino]pyridine-4-carboxylic acid
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MOA Inhibitor
Activity IC50 < 0.1nM
External Link
CID: 76282043
TTD: D0VZ5E
 Compound Name 1190312-92-5 Patented [12]
Synonyms
3-chloro-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid; 3-CHLORO-4-AZAINDOLE-7-CARBOXYLIC ACID; SCHEMBL16157363; US10174026, Example 1; UAFNSWUBMGTOQA-UHFFFAOYSA-N; BDBM320361; ZINC44713035; 3-chloro-1H-pyrrolo[3,2-b] pyridine-7-carboxylic acid
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MOA Inhibitor
Activity IC50 = 5500 nM
External Link
CID: 53412620
TTD: D0ZJ0Z
 Compound Name PBIT Investigative [14]
Synonyms
2514-30-9; 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one; 2-(4-methylphenyl)-1,2-benzothiazol-3-one; MLS000583746; 2-(p-Tolyl)benzo[d]isothiazol-3(2H)-one; 2-(p-tolyl)-1,2-benzothiazol-3-one; SMR000200989; 2-(4-methylphenyl)-1,2-benzothiazol-3(2H)-one; 1,2-Benzisothiazol-3(2H)-one, 2-(4-methylphenyl)-; 2-(4-methylphenyl)-2,3-dihydro-1,2-benzothiazol-3-one; ChemDiv3_007090; AC1LIP69; cid_935415; SCHEMBL2443755; GTPL7026; CHEMBL1336959; CTK0J4356; BDBM34737; AOB6896; DTXSID10359056; MolPort-002-285-696; HMS2576N21
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MOA Inhibitor
External Link
CID: 935415
TTD: D0IQ7Y
Thrombospondin 1 (THBS1) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name ABT-510 Phase 2 [15]
Synonyms
N-Acetyl-N-methyl-glycyl-glycyl-L-valyl-D-alloisoleucyl-L-threonyl-L-norvalyl-L-isoleucyl-L-argininyl-L-proline N-ethylamide
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MOA Modulator
External Link
CID: 6918562
TTD: D0G4MB
DrugBank: DB05434
 Compound Name CVX-045 Phase 2 [16]
Synonyms
CVX-22; CovX-045; PF-4856882; TSP-1 mimetic (cancer), CovX; Thrombospondin-1 mimetic (cancer), CovX; Thrombospondin-1 mimetic (cancer), Pfizer
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MOA Agonist
External Link
TTD: D0S0KP
2C82: Prostate cancer 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name CC-94676 Phase 1 [17]
External Link
TTD: DNY63Z
References
Ref 1 Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression. J Exp Clin Cancer Res. 2020 Oct 21;39(1):223. doi: 10.1186/s13046-020-01735-3.
Ref 2 METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism. Cell Death Discov. 2022 Mar 30;8(1):143. doi: 10.1038/s41420-022-00939-0.
Ref 3 Histone demethylase inhibitors. US9714230.
Ref 4 Histone demethylase inhibitors. US9617242.
Ref 5 IRE-1 inhibitors
Ref 6 Histone demethylase inhibitors. US9725441.
Ref 7 Histone demethylase inhibitors. US10040779.
Ref 8 Histone demethylase inhibitors. US9611221.
Ref 9 Histone demethylase inhibitors. US9604961.
Ref 10 Histone demethylase inhibitors. US10179769.
Ref 11 Histone demethylase inhibitors. US10173996.
Ref 12 Histone demethylase inhibitors. US10174026.
Ref 13 Histone demethylase inhibitors. US9738637.
Ref 14 Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen. J Biol Chem. 2013 Mar 29;288(13):9408-17. doi: 10.1074/jbc.M112.419861. Epub 2013 Feb 13.
Ref 15 A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma. Am J Clin Oncol. 2007 Jun;30(3):303-9. doi: 10.1097/01.coc.0000256104.80089.35.
Ref 16 Antitumor efficacy of a thrombospondin 1 mimetic CovX-body. Transl Oncol. 2011 Aug;4(4):249-57. doi: 10.1593/tlo.11136. Epub 2011 Aug 1.
Ref 17 ClinicalTrials.gov (NCT04428788) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CC-94676 in Subjects With Metastatic Castration-Resistant Prostate Cancer. U.S. National Institutes of Health.