m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03095
 [1]
Histone modification H3K27ac p300 WTAP Direct Enhancement m6A modification NLRP3 NLRP3 WTAP Methylation : m6A sites
m6A Modification:
m6A Regulator Wilms tumor 1-associating protein (WTAP) WRITER
 Regulator Info 
m6A Target NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) View Details
Downstream Gene WTAP View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary Histone acetyltransferase p300 promotes WTAP transcription through Histone H3 lysine 27 acetylation (H3K27ac). WTAP-mediated N6-methyladenosine modification of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) mRNA in kidney injury of diabetic nephropathy. WTAP expression in HK-2 cells was examined with the introduction of C646, a histone acetyltransferase p300 inhibitor.
Responsed Disease Diabetic nephropathy ICD-11: GB61.Z
 Disease Info 
Responsed Drug SETDB1-TTD-IN-1
 Drug Info 
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [2]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
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MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [3]
MOA Inhibitor
External Link
TTD: DT8IL6
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) 4 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Dapansutrile Phase 2 [4]
Synonyms
54863-37-5; OLT1177; UNII-2Z03364G96; 2Z03364G96; Dapansutrile [INN]; Dapansutrile [USAN:INN]; Dapansutrile (USAN/INN); 3-Methylsulfonylpropionitrile; 3-methanesulfonylpropanenitrile; 3-methylsulphonyl-propionitrile; SCHEMBL9934796; CHEMBL3989943; LQFRYKBDZNPJSW-UHFFFAOYSA-N; MolPort-008-545-498; ZINC32005410; Propanenitrile, 3-(methylsulfonyl)-; AKOS010140086; D10920; Z2719319073
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MOA Inhibitor
External Link
CID: 12714644
TTD: D0TH5H
 Compound Name BMS-986299 Phase 1 [5]
MOA Agonist
External Link
TTD: D75LNO
 Compound Name Selnoflast Phase 1 [6]
Synonyms
1-(1-ethylpiperidin-4-yl)sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea; 1-Ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-4-piperidinesulfonamide; 1-ethyl-N-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]piperidine-4-sulfonamide; 2260969-36-4; 4-Piperidinesulfonamide, 1-ethyl-N-(((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)amino)carbonyl)-; 4-Piperidinesulfonamide,1-ethyl-N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-; CHEMBL5095423; CS-0204138; Example 6 [WO2019008025A1]; GTPL12173; HY-132831; MFCD34579587; MS-26540; RG6418; RG-6418; RO7486967; RO-7486967; SCHEMBL20634304; Selnoflast; Selnoflast [INN]; Selnoflast [USAN:INN]; Selnoflast [USAN]; SY347075; T23RPA8WA2; UNII-T23RPA8WA2; WHO 11687
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MOA Inhibitor
External Link
CID: 137402358
TTD: D7KRB9
 Compound Name MCC950 Investigative [7]
Synonyms
210826-40-7; MCC-950; CP-456773; CHEMBL3183703; N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-4-(1-hydroxy-1-methylethyl)-2-furansulfonamide; MCC 950; DSSTox_RID_82252; DSSTox_CID_27301; DSSTox_GSID_47301; SCHEMBL6521858; GTPL8228; DTXSID2047301; MolPort-042-579-517; EX-A1052; BCP15729; Tox21_300462; BDBM50155926; ZINC34025113; AKOS030238802; SB19010; NCGC00254269-01; NCGC00248064-01; HY-12815; CAS-210826-40-7; 1-[4-(1-Hydroxy-1-methylethyl)-2-furylsulfonyl]-3-[(1,2,3,5,6,7-hexahydro-s-indacene)-4-yl]urea
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MOA Inhibitor
Activity IC50 = 5 nM
External Link
CID: 9910393
TTD: D09FGL
GB61: Chronic kidney disease 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Finerenone Approved [8]
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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External Link
CID: 60150535
TTD: D0NV5O
 Compound Name Doxercalciferol Approved [9]
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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External Link
CID: 5281107
TTD: D0G5CF
DrugBank: DB06410
 Compound Name Ferumoxytol Approved [10]
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 [11]
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 [12]
External Link
TTD: D2QVG7
 Compound Name US-APR2020 Phase 2/3 [13]
External Link
TTD: D3YKX2
 Compound Name ALLN-346 Phase 2 [14]
External Link
TTD: DG31WX
 Compound Name Runcaciguat Phase 2 [15]
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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External Link
CID: 134440946
TTD: D2RG4D
 Compound Name GCS-100 Phase 2 [16]
External Link
TTD: D0JW0V
 Compound Name Neo-Kidney Augment Phase 2 [17]
External Link
TTD: D06XFV
 Compound Name LY-2623091 Phase 2 [18]
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 [19]
External Link
TTD: D04AIB
 Compound Name LY3016859 Phase 1/2 [20]
Synonyms
TGF-alpha.epiregulin mAb
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External Link
TTD: D08EIK
 Compound Name ION532 Phase 1 [21]
Synonyms
AZD2373
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External Link
TTD: DR07FQ
 Compound Name MEDI8367 Phase 1 [22]
External Link
TTD: D37AYZ
References
Ref 1 WTAP-mediated N(6)-methyladenosine modification of NLRP3 mRNA in kidney injury of diabetic nephropathy. Cell Mol Biol Lett. 2022 Jun 27;27(1):51. doi: 10.1186/s11658-022-00350-8.
Ref 2 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 3 Clinical pipeline report, company report or official report of FORMA Therapeutics.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 National Cancer Institute Drug Dictionary (drug name BMS-986299).
Ref 6 Clinical pipeline report, company report or official report of Roche
Ref 7 A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55.
Ref 8 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 215341.
Ref 9 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 10 ClinicalTrials.gov (NCT01942460) Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients. U.S. National Institutes of Health.
Ref 11 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 12 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 13 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 14 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 15 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 16 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 17 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 18 ClinicalTrials.gov (NCT02194465) A Study of LY2623091 in Participants With High Blood Pressure. U.S. National Institutes of Health.
Ref 19 Clinical pipeline report, company report or official report of Ardelyx.
Ref 20 ClinicalTrials.gov (NCT01774981) Study of LY3016859 in Participants With Diabetic Nephropathy. U.S. National Institutes of Health.
Ref 21 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 22 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.