Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05424
[1]
m6A modification MALAT1 MALAT1 METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA MALAT1 MIR145  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) LncRNA View Details
Regulated Target MicroRNA 145 (MIR145) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Renal fibrosis is a key factor in chronic kidney disease (CKD). METTL3 upregulates Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in an m6A-dependent manner and MALAT1/MicroRNA 145 (MIR145)/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
Responsed Drug Dihydroartemisinin
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
GB61: Chronic kidney disease 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Finerenone Approved [2]
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
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 Compound Name Doxercalciferol Approved [3]
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)
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 Compound Name Ferumoxytol Approved [4]
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
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 Compound Name Ferric citrate Approved [5]
Synonyms
Nephoxil; Serene; Zerenex; JTT-751; KRX-0502; PBF-1681; Hyperphosphatemia therapy, Panion/Keryx
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 Compound Name REACT Phase 3 [6]
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 Compound Name US-APR2020 Phase 2/3 [7]
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 Compound Name ALLN-346 Phase 2 [8]
External Link
 Compound Name Runcaciguat Phase 2 [9]
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
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 Compound Name GCS-100 Phase 2 [10]
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 Compound Name Neo-Kidney Augment Phase 2 [11]
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 Compound Name LY-2623091 Phase 2 [12]
Synonyms
Chronic renal disease therapy, Eli Lilly
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 Compound Name AZD1772//RDX5791 Phase 2 [13]
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 Compound Name LY3016859 Phase 1/2 [14]
Synonyms
TGF-alpha.epiregulin mAb
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 Compound Name ION532 Phase 1 [15]
Synonyms
AZD2373
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 Compound Name MEDI8367 Phase 1 [16]
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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 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215341.
Ref 3 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 4 ClinicalTrials.gov (NCT01942460) Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients. U.S. National Institutes of Health.
Ref 5 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 6 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 7 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 8 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 9 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 10 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 11 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 12 ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health.
Ref 13 Clinical pipeline report, company report or official report of Ardelyx.
Ref 14 ClinicalTrials.gov (NCT01774981) Study of LY3016859 in Participants With Diabetic Nephropathy. U.S. National Institutes of Health.
Ref 15 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 16 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.