m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05484
 [1]
m6A modification Circ_CUX1 Circ_CUX1 METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA Circ_CUX1 CASP1  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target hsa_circ_0081609 (circ_CUX1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa_circ_0081609 (Circ_CUX1) circRNA View Details
Regulated Target Caspase-1 (CASP1) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary METTL3-mediated m6A modification plays a key role in stabilizing the expression of hsa_circ_0081609 (circ_CUX1), thereby inhibiting the expression of Caspase-1 (CASP1) and conferring the radiotherapy resistance of hypopharyngeal squamous cell carcinoma.
Responsed Disease Hypopharyngeal cancer ICD-11: 2B6D
 Disease Info 
In-vitro Model
 SCC-4 Tongue squamous cell carcinoma Homo sapiens CVCL_1684
SCC-9 Tongue squamous cell carcinoma Homo sapiens CVCL_1685
SCC-15 Tongue squamous cell carcinoma Homo sapiens CVCL_1681
CLA-27 cell line (The head and neck tumor cell lines)
SAS Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Tca8113 Endocervical adenocarcinoma Homo sapiens CVCL_6851
HOK Normal Hexagrammos otakii CVCL_YE19
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Caspase-1 (CASP1) 14 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Belnacasan Phase 2 [2]
Synonyms
Second generation ICE inhibitors, Vertex; VRT-043198; VRT-43198; VX-765; VX-765)
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MOA Inhibitor
External Link
CID: 11398092
TTD: D0HK3N
 Compound Name PRALNACASAN Phase 2 [3]
Synonyms
VX-740; UNII-N986NI319S; 192755-52-5; N986NI319S; HMR3480/VX-740; Pralnacasan [USAN:INN]; HMR 3480; VX 470; Pralnacasan (USAN/INN); AC1L4A1A; SCHEMBL142187; GTPL6467; CHEMBL437526; DTXSID60172873; HMR3480; HMR-3480; BDBM50189360; AKOS030230853; DB04875; D08978; (4S,7S)-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carboxamide
    Click to Show/Hide
MOA Modulator
Activity IC50 = 3.6 nM
External Link
CID: 153270
TTD: D0U6WQ
DrugBank: DB04875
 Compound Name Nivocasan Phase 2 [4]
Synonyms
GS-9450; LB-84451
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MOA Modulator
External Link
CID: 11633038
TTD: D0Z2JF
DrugBank: DB12720
 Compound Name AC-201 Phase 2 [5]
MOA Inhibitor
External Link
TTD: D0WP2R
 Compound Name Ac-YVAD-FMK Patented [6]
MOA Inhibitor
External Link
TTD: D04KIH
 Compound Name Ac-YVAD-cmk Patented [6]
MOA Inhibitor
External Link
TTD: D07AVV
 Compound Name VE-16084 Terminated [7]
Synonyms
ICE inhibitors, Sanofi Winthrop; WIN-67694
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MOA Inhibitor
External Link
CID: 10009105
TTD: D0A3HF
 Compound Name L-709049 Terminated [8]
Synonyms
Ac-Yvad-cho; 143313-51-3; Acetyl-tyrosyl-valyl-alanyl-aspartal; Caspase-1 Inhibitor I; CHEMBL37630; Ac-Tyr-Val-Ala-Asp-H; IL-1beta Converting Enzyme (ICE) Inhibitor I; acetyl-Tyr-Val-Ala-Asp-aldehyde; N-acetyl-Tyr-Val-Ala-Asp-aldehyde; (3S)-3-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanamido]-3-methylbutanamido]propanamido]-4-oxobutanoic acid; Ac-Tyr-Val-Ala-Asp-Aldehyde; AC1NSK2K; SCHEMBL4349143; BDBM10355; MolPort-016-580-695; N-acetyl-Tyr-Val-Ala-Asp aldehyde; ZINC3915255; 1600AH; NCGC00167338-01
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 0.7 nM
External Link
CID: 5311139
TTD: D0F9FA
 Compound Name SDZ-224-015 Terminated [9]
Synonyms
VE-13045
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MOA Modulator
External Link
CID: 101925102
TTD: D0K1CL
 Compound Name YVAD Investigative [10]
MOA Inhibitor
External Link
CID: 9847365
TTD: D0B3WF
 Compound Name Z-YVAD-CHO Investigative [11]
Synonyms
CHEMBL159822
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MOA Inhibitor
Activity Ki = 180 nM
External Link
CID: 44407073
TTD: D0P3XJ
 Compound Name Z-VAD-CHO Investigative [11]
Synonyms
CHEMBL320954; ZVAD-CHO; BDBM50176519; (S)-3-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-butyric acid
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MOA Inhibitor
Activity Ki = 8 nM
External Link
CID: 10112904
TTD: D0X8XO
 Compound Name Z-YVAD-FMK Investigative [12]
Synonyms
benzyloxycarbonyl-Tyr-Val-Ala-Asp(OMe)-fluoromethylketone; caspase-1 Inhibitor VI
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MOA Inhibitor
External Link
CID: 644196
TTD: D0YX4V
 Compound Name M826 Investigative [13]
Synonyms
compound 4sx
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MOA Inhibitor
External Link
CID: 9851134
TTD: D00YNW
References
Ref 1 N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway. Cell Death Dis. 2021 Mar 19;12(4):298. doi: 10.1038/s41419-021-03558-2.
Ref 2 (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydr... J Pharmacol Exp Ther. 2007 May;321(2):509-16.
Ref 3 Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis Cartilage. 2003 Oct;11(10):738-46.
Ref 4 Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats. Apoptosis. 2013 Dec;18(12):1481-91.
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59.
Ref 7 Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine. 1996 May;8(5):377-86.
Ref 8 Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1). Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90.
Ref 9 Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme. Br J Pharmacol. 1995 Jun;115(4):601-6.
Ref 10 Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am J Physiol. 1999 Nov;277(5 Pt 2):R1435-43.
Ref 11 Tethering identifies fragment that yields potent inhibitors of human caspase-1. Bioorg Med Chem Lett. 2006 Feb;16(3):559-62.
Ref 12 Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. J Nutr. 2002 Jul;132(7):1812-8.
Ref 13 Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1173-80. doi: 10.1016/j.bmcl.2004.12.006.