m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03255
 [1]
m6A modification KDM5B KDM5B YTHDC2 : m6A sites Direct Inhibition Histone modification H3K4me3 KDM5B SIRT3
m6A Modification:
m6A Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
m6A Target Lysine-specific demethylase 5B (KDM5B)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 5B (KDM5B) ERASER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene SIRT3 View Details
Crosstalk Relationship m6A  →  Histone modification Inhibition
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary YTHDC2 over expression decreased Lysine-specific demethylase 5B (KDM5B) mRNA stability in an m6A-dependent manner. Our results also revealed that YTHDC2 overexpression resulted in reduced ROS level and increased ATP level, PDH activity, OCR and ECAR in HG-treated Schwann cells, while these effects were reversed by KDM5B overexpression. KDM5B inhibited SIRT3 transcription by Histone H3 lysine 4 trimethylation (H3K4me3).
Responsed Disease Diabetic nephropathy ICD-11: GB61.Z
 Disease Info 
Cell Process mRNA stability
In-vitro Model
RSC96
 N.A. Rattus norvegicus CVCL_4694
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Lysine-specific demethylase 5B (KDM5B) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PBIT Investigative [2]
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
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CID: 935415
TTD: D0IQ7Y
GB61: Chronic kidney disease 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Finerenone Approved [3]
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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CID: 60150535
TTD: D0NV5O
 Compound Name Doxercalciferol Approved [4]
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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CID: 5281107
TTD: D0G5CF
DrugBank: DB06410
 Compound Name Ferumoxytol Approved [5]
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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External Link
CID: 14789
TTD: D06CTM
 Compound Name Ferric citrate Approved [6]
Synonyms
Nephoxil; Serene; Zerenex; JTT-751; KRX-0502; PBF-1681; Hyperphosphatemia therapy, Panion/Keryx
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External Link
CID: 61300
TTD: D04CJL
DrugBank: DB09162
 Compound Name REACT Phase 3 [7]
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TTD: D2QVG7
 Compound Name US-APR2020 Phase 2/3 [8]
External Link
TTD: D3YKX2
 Compound Name ALLN-346 Phase 2 [9]
External Link
TTD: DG31WX
 Compound Name Runcaciguat Phase 2 [10]
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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CID: 134440946
TTD: D2RG4D
 Compound Name GCS-100 Phase 2 [11]
External Link
TTD: D0JW0V
 Compound Name Neo-Kidney Augment Phase 2 [12]
External Link
TTD: D06XFV
 Compound Name LY-2623091 Phase 2 [13]
Synonyms
Chronic renal disease therapy, Eli Lilly
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External Link
CID: 42636651
TTD: D05RZE
DrugBank: DB15367
 Compound Name AZD1772//RDX5791 Phase 2 [14]
External Link
TTD: D04AIB
 Compound Name LY3016859 Phase 1/2 [15]
Synonyms
TGF-alpha.epiregulin mAb
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External Link
TTD: D08EIK
 Compound Name ION532 Phase 1 [16]
Synonyms
AZD2373
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External Link
TTD: DR07FQ
 Compound Name MEDI8367 Phase 1 [17]
External Link
TTD: D37AYZ
References
Ref 1 The m(6)A reader YTHDC2 promotes SIRT3 expression by reducing the stabilization of KDM5B to improve mitochondrial metabolic reprogramming in diabetic peripheral neuropathy. Acta Diabetol. 2023 Mar;60(3):387-399. doi: 10.1007/s00592-022-01990-0. Epub 2022 Dec 27.
Ref 2 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 3 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215341.
Ref 4 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 5 ClinicalTrials.gov (NCT01942460) Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients. U.S. National Institutes of Health.
Ref 6 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 7 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 8 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 9 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 10 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 11 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 12 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 13 ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health.
Ref 14 Clinical pipeline report, company report or official report of Ardelyx.
Ref 15 ClinicalTrials.gov (NCT01774981) Study of LY3016859 in Participants With Diabetic Nephropathy. U.S. National Institutes of Health.
Ref 16 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 17 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.