m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05930
 [1]
m6A modification MALAT1 MALAT1 METTL3 Methylation : m6A sites Indirect Inhibition Non-coding RNA miR-145 FAK  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator MicroRNA 145 (MIR145) microRNA View Details
Regulated Target Focal adhesion kinase 1 (FAK) View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators indirectly modulate the functionality of ncRNAs through downstream signaling pathways
Crosstalk Summary m6A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m6A modification on Metastasis associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1/MIR145/Focal adhesion kinase 1 (FAK) pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Responsed Drug Dihydroartemisinin
 Drug Info 
Cell Process Cell migration
Cells proliferation
In-vitro Model
 HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Protein tyrosine kinase 2 (PTK2) 11 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name VS-6063 Phase 2 [2]
Synonyms
Defactinib hydrochloride; 1073160-26-5; Defactinib (hydrochloride); UNII-L2S469LM49; Defactinib hydrochloride [USAN]; L2S469LM49; Defactinib hydrochloride (USAN); Benzamide, N-methyl-4-[[4-[[[3-[methyl(methylsulfonyl)amino]-2-pyrazinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-, hydrochloride; Defactinib HCl; Benzamide, N-methyl-4-((4-(((3-(methyl(methylsulfonyl)amino)-2-pyrazinyl)methyl)amino)-5-(trifluoromethyl)-2-pyrimidinyl)amino)-, hydrochloride (1:1); Benzamide, N-methyl-4-[[4-[[[3-[methyl(methylsu
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 25117126
TTD: D0Y1UO
DrugBank: DB12282
 Compound Name BI-853520 Phase 1 [3]
MOA Modulator
External Link
TTD: D00KNI
 Compound Name PF-562271 Phase 1 [4]
Synonyms
PF-00562271
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1 nM
External Link
CID: 11713159
TTD: D01SJT
 Compound Name VS-4718 Phase 1 [5]
Synonyms
PND-1186
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1.5 nM
External Link
CID: 25073775
TTD: D0A6VD
DrugBank: DB15273
 Compound Name GSK-2256098 Phase 1 [6]
Synonyms
Focal adhesion kinase inhibitor (oral, cancer), GlaxoSmithKline
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 46214930
TTD: D0B9MR
 Compound Name CEP-37440 Phase 1 [3]
Synonyms
Dual ALK/FAK inhibitor (cancer), Cephalon; Dual anaplastic lymphoma kinase/focal adhesion kinase inhibitor (cancer),Cephalon
    Click to Show/Hide
MOA Modulator
Activity IC50 = 80 nM
External Link
CID: 71721648
TTD: D0N6NM
DrugBank: DB13060
 Compound Name IN10018 Phase 1 [7]
MOA Inhibitor
External Link
TTD: D1EW3O
 Compound Name 1,2,4-triazolo[1,5a]pyridine derivative 1 Patented [8]
Synonyms
PMID27774824-Compound-Figure8compoundA
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1100 nM
External Link
TTD: D07XYI
 Compound Name PMID23414845C30 Investigative [9]
Synonyms
4i4f; GTPL7864; BDBM50430287; 1BR
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2200 nM
External Link
CID: 70698427
TTD: D0AY0F
 Compound Name PF-228 Investigative [10]
Synonyms
869288-64-2; PF-573228; PF 573228; PF573228; CHEMBL514554; 3,4-Dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone; 6-((4-((3-(Methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; 6-[4-(3-Methanesulfonyl-benzylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3,4-dihydro-1H-quinolin-2-one
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 50 nM
External Link
CID: 11612883
TTD: D02QAZ
 Compound Name BMS-536924 Investigative [11]
MOA Inhibitor
Activity IC50 = 150 nM
External Link
CID: 135440466
TTD: D0M4SY
GB61: Chronic kidney disease 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Finerenone Approved [12]
Synonyms
UNII-DE2O63YV8R; BAY 94-8862; 1050477-31-0; BAY94-8862; DE2O63YV8R; Finerenone [USAN:INN]; Finerenone (JAN/USAN/INN); SCHEMBL8157011; GTPL8678; DTXSID10146928; J3.584.878I; D10633; 1,6-Naphthyridine-3-carboxamide, 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1,4-dihydro-2,8-dimethyl-, (4S)-;1,6-Naphthyridine-3-carboxamide, 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1,4-dihydro-2,8-dimethyl-, (4S)-; 1,6-Naphthyridine-3-carboxamide, 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1,4-dihydro-2,8-dimethyl-, (4S)-; (4S)-4-(4-cyano-2-metho
    Click to Show/Hide
External Link
CID: 60150535
TTD: D0NV5O
 Compound Name Doxercalciferol Approved [13]
Synonyms
Doxcercalciferol; Hectorol; Doxercalciferol [INN]; TSA 840; BCI-101; Doxercalciferol (INN); Hectorol (TN); (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol; (5Z,7E,22E)-9,10-Secoergosta-5,7,10(19),22-tetraene-1alpha,3beta-diol; 1-Hydroxyergocalciferol; 1-alpha-Hydroxyvitamin D2; 1alpha-Hydroxyergocalciferol; 1alpha-OH-D2; 9,10-Secoergosta-5,7,10(19),22-tetraene-1,3-diol,(1-alpha,3-beta,5Z,7E,22E)
    Click to Show/Hide
External Link
CID: 5281107
TTD: D0G5CF
DrugBank: DB06410
 Compound Name Ferumoxytol Approved [14]
Synonyms
MAGNETITE; Magnetic oxide; Ferrosoferric oxide; Magnetite (Fe3O4); Magnetic Black; Iron Black; Fenosoferric oxide; Black Iron BM; Meramec M 25; Black Gold F 89; RB-BL; 11557 Black; CCRIS 4376; H 3S; EPT 500; EINECS 215-169-8; KN 320; 1309-38-2; iron(ii; ferro ferric oxide; ferric ferrous oxide; Iron ores, magnetite; Ferumoxytol [USAN]; Eisen(II,III)-oxid; KBC 100 (mineral); Code 7228; CHEBI:50821; 1317-61-9 (Parent); LS-88610; 174794-75-3; 122303-97-3; 90577-09-6; 73904-98-0; 151820-32-5; 137263-94-6; 124364-57-4
    Click to Show/Hide
External Link
CID: 14789
TTD: D06CTM
 Compound Name Ferric citrate Approved [15]
Synonyms
Nephoxil; Serene; Zerenex; JTT-751; KRX-0502; PBF-1681; Hyperphosphatemia therapy, Panion/Keryx
    Click to Show/Hide
External Link
CID: 61300
TTD: D04CJL
DrugBank: DB09162
 Compound Name REACT Phase 3 [16]
External Link
TTD: D2QVG7
 Compound Name US-APR2020 Phase 2/3 [17]
External Link
TTD: D3YKX2
 Compound Name ALLN-346 Phase 2 [18]
External Link
TTD: DG31WX
 Compound Name Runcaciguat Phase 2 [19]
Synonyms
(3S)-3-(4-Chloro-3-(((2S,3R)-2-(4-chlorophenyl-4,4,4- trifluoro-3-methylbutanoyl)amino)phenyl)-3- cyclopropylpropanoic acid; (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid; (3S)-3-[4-chloro-3-[[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino]phenyl]-3-cyclopropylpropanoic acid; 1402936-61-1; 5EZ01YDT5S; AC-37098; AKOS040742586; BAY 1101042; BAY1101042; BAY-1101042; BENZENEPROPANOIC ACID, 4-CHLORO-3-(((2S,3R)-2-(4-CHLOROPHENYL)-4,4,4-TRIFLUORO-3-METHYL-1-OXOBUTYL)AMINO)-.BETA.-CYCLOPROPYL-, (.BETA.S)-; Benzenepropanoic acid, 4-chloro-3-(((2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methyl-1-oxobutyl)amino)-beta-cyclopropyl-, (betaS)-; CHEMBL4650322; compound 45 [PMID: 33872507]; CS-0086784; GTPL12359; HY-109136; MS-29070; Runcaciguat; Runcaciguat [INN]; SCHEMBL20075857; UNII-5EZ01YDT5S; XZ7
    Click to Show/Hide
External Link
CID: 134440946
TTD: D2RG4D
 Compound Name GCS-100 Phase 2 [20]
External Link
TTD: D0JW0V
 Compound Name Neo-Kidney Augment Phase 2 [21]
External Link
TTD: D06XFV
 Compound Name LY-2623091 Phase 2 [22]
Synonyms
Chronic renal disease therapy, Eli Lilly
    Click to Show/Hide
External Link
CID: 42636651
TTD: D05RZE
DrugBank: DB15367
 Compound Name AZD1772//RDX5791 Phase 2 [23]
External Link
TTD: D04AIB
 Compound Name LY3016859 Phase 1/2 [24]
Synonyms
TGF-alpha.epiregulin mAb
    Click to Show/Hide
External Link
TTD: D08EIK
 Compound Name ION532 Phase 1 [25]
Synonyms
AZD2373
    Click to Show/Hide
External Link
TTD: DR07FQ
 Compound Name MEDI8367 Phase 1 [26]
External Link
TTD: D37AYZ
References
Ref 1 m(6)A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway. Aging (Albany NY). 2020 Mar 23;12(6):5280-5299. doi: 10.18632/aging.102950. Epub 2020 Mar 23.
Ref 2 Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. doi: 10.1093/jnci/djt210. Epub 2013 Sep 23.
Ref 3 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 4 Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45. doi: 10.1158/1535-7163.MCT-11-0261. Epub 2011 Sep 8.
Ref 5 FAK Inhibition disrupts a Beta5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. Mol Cancer Ther. 2014 Aug;13(8):2050-61. doi: 10.1158/1535-7163.MCT-13-1063. Epub 2014 Jun 4.
Ref 6 A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. doi: 10.4161/15384101.2014.949550.
Ref 7 Clinical pipeline report, company report or official report of InxMed.
Ref 8 Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1. Expert Opin Ther Pat. 2017 Feb;27(2):127-143. doi: 10.1080/13543776.2017.1252753. Epub 2016 Nov 7.
Ref 9 Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1779-85.
Ref 10 Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52. doi: 10.1074/jbc.M606695200. Epub 2007 Mar 28.
Ref 11 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005 Sep 8;48(18):5639-43. doi: 10.1021/jm050392q.
Ref 12 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215341.
Ref 13 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: 2790).
Ref 14 ClinicalTrials.gov (NCT01942460) Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients. U.S. National Institutes of Health.
Ref 15 ClinicalTrials.gov (NCT02268994) KRX-0502 (Ferric Citrate) for the Treatment of IDA in Adult Subjects With NDD-CKD. U.S. National Institutes of Health.
Ref 16 ClinicalTrials.gov (NCT05099770) A Phase 3 Randomized Controlled Study of Renal Autologous Cell Therapy (REACT) in Subjects With Type 2 Diabetes and Chronic Kidney Disease (REGEN-006). U.S.National Institutes of Health.
Ref 17 ClinicalTrials.gov (NCT05407389) An Open-Label Rollover Extension Phase 2 Clinical Trial To Evaluate The Long-Term Safety And Efficacy Of KT-301 (Formerly US-APR2020) In Subjects With CKD IV Completing The US-APR2020-01 Study. U.S.National Institutes of Health.
Ref 18 ClinicalTrials.gov (NCT04987294) A Randomized, Double-Blind, Placebo-Controlled Study of ALLN-346 (Engineered Urate Oxidase) in Hyperuricemic Subjects With Gout and Mild to Moderate Chronic Kidney Disease. U.S.National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT04507061) A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Individually Titrated Oral Doses of Runcaciguat in Subjects With Clinical Diagnosis of Chronic Kidney Disease With Diabetes and/or Hypertension and at Least One Cardiovascular Comorbidity. U.S.National Institutes of Health.
Ref 20 ClinicalTrials.gov (NCT01843790) A Phase 2a Study of Weekly Doses of GCS-100 in Patients With Chronic Kidney Disease. U.S. National Institutes of Health.
Ref 21 ClinicalTrials.gov (NCT02525263) Autologous Neo-Kidney Augment (NKA) in Patients With Type 2 Diabetes and Chronic Kidney Disease (CKD) (RMCL-CL001). U.S. National Institutes of Health.
Ref 22 ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health.
Ref 23 Clinical pipeline report, company report or official report of Ardelyx.
Ref 24 ClinicalTrials.gov (NCT01774981) Study of LY3016859 in Participants With Diabetic Nephropathy. U.S. National Institutes of Health.
Ref 25 ClinicalTrials.gov (NCT05351047) A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD2373 Following Multiple Ascending Dose Administration to Healthy Male Participants of Sub-Saharan West African Ancestry. U.S.National Institutes of Health.
Ref 26 ClinicalTrials.gov (NCT04365218) A Phase I Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of MEDI8367 Administered as Single Ascending Doses in Healthy Subjects, and as a Single Dose in Healthy Subjects of Japanese-descent and in Subjects With Chronic Kidney Disease. U.S.National Institutes of Health.