m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03215
 [1]
Histone modification H3K27ac KAT1 YTHDF2 Direct Enhancement m6A modification ITGB1 ITGB1 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Integrin beta-1 (ITGB1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase type B catalytic subunit (HAT1) WRITER View Details
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) View Details
Downstream Gene YTHDF2 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 HAT1 activated the transcription activity of YTHDF2 through Histone H3 lysine 27 acetylation (H3K27ac) of the promoter, and YTHDF2 triggered the instability of Integrin beta-1 (ITGB1) mRNA to induce mRNA degradation in an m6A manner.
Responsed Disease Diabetic retinopathy ICD-11: 9B71.0
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process RNA stability
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Integrin beta-1 (ITGB1) 6 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name 131I-radretumab Phase 1/2 [2]
Synonyms
L-19; L-19-IgG1; L-19-SIP; Single chain Fv antibody fragment-based radioimmunotherapeutics, ETH Zurich/Bayer Schering/Philogen; Single chain Fv antibody fragment-based radioimmunotherapeutics, ETH Zurich/Schering/Philogen; L-19 based radioimmunotherapeutics (cancer), ETH Zurich/Bayer Schering/Philogen; L-19 based radioimmunotherapeutics (cancer), ETH Zurich/Schering/Philogen; ScFv-based radioimmunotherapeutics (cancer), ETH Zurich/Bayer Schering/Philogen; ScFv-based radioimmunotherapeutics (cancer), ETH Zurich/Schering/Philogen; 125I-L-19; 125I-L-19-IgG1; 125I-L-19-SIP
    Click to Show/Hide
External Link
TTD: D0H4GT
 Compound Name OS2966 Phase 1 [3]
MOA Inhibitor
External Link
TTD: DB8MR6
 Compound Name JSM 6427 Phase 1 [4]
MOA Antagonist
External Link
TTD: D0ZT4J
 Compound Name MK-0668 Investigative [5]
Synonyms
UNII-S441P37178; CHEMBL506044; S441P37178; 865110-07-2; SCHEMBL13884454; BDBM50423686; N-(N-((3-Cyanophenyl)sulfonyl)-4(R)-cyclobutylamino-(l)-prolyl)-4-((3',5'-dichloroisonicotinoyl) amino)-(l)-phenylalanine; L-Phenylalanine, (4R)-1-((3-cyanophenyl)sulfonyl)-4-(cyclobutylamino)-L-prolyl-4-(((3,5-dichloro-4-pyridinyl)carbonyl)amino)-
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11433918
TTD: D09XED
 Compound Name SB-265123 Investigative [6]
Synonyms
CHEMBL288493; SCHEMBL244383; HODBWQCCKYDYPY-NRFANRHFSA-N; {3-[3-(Pyridin-2-ylamino)-propoxy]-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl}-acetic acid; BDBM50078714; {(S)-3-[3-(Pyridin-2-ylamino)-propoxy]-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl}-acetic acid; (S)-10,11-Dihydro-3-[3-(pyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[a,d]cycloheptene-10-acetic acid
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MOA Inhibitor
External Link
CID: 9952958
TTD: D0R3CY
 Compound Name C(-GRGDfL-) Investigative [7]
Synonyms
CHEMBL235999
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 15409414
TTD: D0B4JU
9B71: Retinopathy 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name SHP607 Phase 2 [8]
External Link
TTD: D0R1JO
 Compound Name RST-001 Phase 1/2 [9]
Synonyms
ChR2 gene therapy (retinopathy), RetroSense; AAV-based ChR2 gene therapy (retinopathy), RetroSense; Channelrhodopsin-2 gene therapy (retinopathy), RetroSense
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External Link
TTD: D0RM6A
 Compound Name ReN-003 Phase 1/2 [10]
Synonyms
Stem cell therapy (retinal diseases), ReNeuron
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External Link
TTD: D03OVN
 Compound Name PMID28621580-Compound-WO2015089220C70 Patented [11]
External Link
TTD: D07AVU
 Compound Name SIR-1076 Preclinical [12]
Synonyms
Antioxidants (topical, retinal oxidative stress), Sirion Therapeutics
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External Link
TTD: D06RVY
 Compound Name CytoRet Investigative [10]
Synonyms
Retinal cell therapy (retinal disease), International Stem Cell; Retinal layers (parthenogenetic stem-cell derived), ISCO
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External Link
TTD: D0V4YT
 Compound Name LPO-1010CSR Investigative [10]
External Link
TTD: D0MH8K
 Compound Name INDUS-815C Investigative [13]
Synonyms
VEGF modulator (age related macular degeneration/retinopathy), Indus Biotech; INDUS-815C (Huntington's disease), Indus Biotech; INDUS-815C (age related macular degeneration/retinopathy), Indus Biotech; SIRT2 inhibtior (Parkinson's disease/dementia/Huntington's disease), Indus Biotech; NAD-dependent deacetylase sirtuin-2inhibitor (Parkinson's disease/dementia/Huntington's disease), Indus Biotech
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External Link
TTD: D0IR8J
 Compound Name SF-113 Investigative [10]
External Link
TTD: D0I2AD
 Compound Name SF-106 Investigative [10]
External Link
TTD: D07DRO
 Compound Name Gene therapy, retinopathy, Investigative [10]
Synonyms
Gene therapy (retinopathy)
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External Link
TTD: D04ENF
 Compound Name Superoxide dismutase mimetics Investigative [10]
Synonyms
INO-6001; INO-6002; Superoxide dismutase mimetics (retinal disease); Superoxide dismutase mimetics (retinal disease), Inotek; Superoxide dismutase mimetics (age-related macular degeneration/diabetic retinopathy/diabetic macular edema), Inotek
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External Link
TTD: D03KRF
References
Ref 1 KAT1 triggers YTHDF2-mediated ITGB1 mRNA instability to alleviate the progression of diabetic retinopathy. Pharmacol Res. 2021 Aug;170:105713. doi: 10.1016/j.phrs.2021.105713. Epub 2021 Jun 5.
Ref 2 Radretumab radioimmunotherapy in patients with brain metastasis: a 124I-L19SIP dosimetric PET study. Cancer Immunol Res. 2013 Aug;1(2):134-43. doi: 10.1158/2326-6066.CIR-13-0007. Epub 2013 May 20.
Ref 3 Convection-Enhanced Delivery of a First-in-Class Anti-Beta1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging. Pharmaceutics. 2020 Dec 30;13(1):40. doi: 10.3390/pharmaceutics13010040.
Ref 4 An alpha5beta1 integrin inhibitor attenuates glioma growth. Mol Cell Neurosci. 2008 Dec;39(4):579-85. doi: 10.1016/j.mcn.2008.08.005. Epub 2008 Sep 4.
Ref 5 Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3',5'-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5803-6. doi: 10.1016/j.bmcl.2009.07.111. Epub 2009 Jul 28.
Ref 6 Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model. Bioorg Med Chem Lett. 1999 Jul 5;9(13):1807-12. doi: 10.1016/s0960-894x(99)00283-8.
Ref 7 Multiple N-methylation by a designed approach enhances receptor selectivity. J Med Chem. 2007 Nov 29;50(24):5878-81. doi: 10.1021/jm701044r. Epub 2007 Nov 1.
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 ClinicalTrials.gov (NCT02556736) RST-001 Phase I/II Trial for Retinitis Pigmentosa.
Ref 10 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
Ref 11 VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016). Expert Opin Ther Pat. 2017 Sep;27(9):987-1004. doi: 10.1080/13543776.2017.1344215. Epub 2017 Jun 23.
Ref 12 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028168)
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. (Target id: 2708).