924296-19-5 Usage
Biological Activity
dubs-in-2 is a potent deubiquitinase enzyme inhibitor.usp7 (or hausp) associated with the protein mdm2 (an e3 ubiquitin ligase) recognizes the n-terminal transactivation domain of the p53 tumor suppressor and elicites its degradation by ubiquitination. usp7 also interacts with directly essential viral proteins (p53, foxo4, pten) and oncogenic pathways. in addition, phenotypes connected with usp7 silencing strongly reveal that targeting usp7 by small-molecule inhibitors may be an potential direction for antiviral and anticancer therapies. usp8 (or ubpy) interacts with many substrates, such as the epidermal growth factor receptor (egfr), an essential for the regulating cell survival, proliferation, and differentiation pathways), and is a critical regulator of receptor endocytosis and trafficking [1].dubs-in-2 as potent inhibitors of usp7 and usp8 deubiquitinating enzymes was identified functionalized cyanopyrazines by high-throughput screening of 65092 chemically diverse compounds for activity toward full-length usp7 cysteine protease in a fluorescence-based biochemical assay [1].
in vitro
human usp7 and usp8 enzymes in baculovirus-infected insect cells were overexpressed in their full-length forms, then purified by the his-tag affinity chromatography procedure. using ubiquitin c-terminal 7-amido-4-methylcoumarin (ub–amc) evaluates inhibition of usp7 and usp8 deubiquitinating activity. ub–amc is hydrolyzed by deubiquitinating enzymes, thus releasing amc. ic50 values were calculated based on dose–response curve after dilution of DUBs-IN-2 in eight final concentrations, ranging from 100 mm to 10 nm [1].
IC 50
s: 7.2 m/0.93 m for usp7/usp8, respectively.
references
[1] colombo m, vallese s, peretto i, jacq x, rain jc, colland f, guedat p. synthesis and biological evaluation of 9-oxo-9h-indeno[1,2-b]pyrazine-2,3-dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes. chemmedchem. 2010 apr 6;5(4):552-8.
Check Digit Verification of cas no
The CAS Registry Mumber 924296-19-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,4,2,9 and 6 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 924296-19:
(8*9)+(7*2)+(6*4)+(5*2)+(4*9)+(3*6)+(2*1)+(1*9)=185
185 % 10 = 5
So 924296-19-5 is a valid CAS Registry Number.
924296-19-5Relevant academic research and scientific papers
Synthesis and biological evaluation of 9-oxo-9hindeno[1,2-b]pyrazine-2,3- dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes
Colombo, Matteo,Vallese, Stefania,Peretto, Ilaria,Jacq, Xavier,Rain, Jean-Christophe,Colland, Frederic,Guedat, Philippe
experimental part, p. 552 - 558 (2010/12/25)
High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3- dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.
Novel cysteine protease inhibitors and their therapeutic applications
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Page/Page column 24, (2008/06/13)
The present invention concerns new compounds of formula (I), their process of preparation and their therapeutic use.
Novel cysteine protease inhibitors and their therapeutic applications
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Page/Page column 17, (2008/06/13)
The present invention concerns new compounds of formula (I), their process of preparation and their therapeutic use.
