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10.18632/oncotarget.11934

http://scihub22266oqcxt.onion/10.18632/oncotarget.11934
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C5470962!5470962!27626700
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suck abstract from ncbi


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pmid27626700      Oncotarget 2017 ; 8 (21): 34223-35
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  • Isoliquiritigenin suppresses human T Lymphocyte activation via covalently binding cysteine 46 of I?B kinase #MMPMID27626700
  • Yan F; Yang F; Wang R; Yao XJ; Bai L; Zeng X; Huang J; Wong VKW; Lam CWK; Zhou H; Su X; Liu J; Li T; Liu L
  • Oncotarget 2017[May]; 8 (21): 34223-35 PMID27626700show ga
  • The efficacious practice of precision personalized medicine requires a more exact understanding of the molecular mechanisms of drug, hence then it is necessary to identify the binding site of the drugs derived from natural sources. In the study, we investigated the suppressive effect and underlying mechanism of isoliquiritigenin (2?,4?,4-trihydroxychalcone; ILG), a phyto-flavonoid, on human T lymphocyte activation in vitro and in vivo. The results showed that ILG dose-dependently suppressed human T cell activation via suppressing I?B? phosphorylation and degradation, NF-?B nuclear translocation and IKK? activity. Molecular docking results predicted that cysteine 46 (Cys-46) is probably the binding site of ILG on IKK?, and this prediction has been validated by competition assay and kinase assay. To further verify the binding site of this compound in vivo, IKK?C46A transgenic (IKK?C46A) mice were generated. We found that ILG had a less potent immune-suppressive effect in homozygous IKK?C46A mice than IKK? wild type (IKK? wt) littermates with the delay-type hypersensitivity (DTH), suggesting that ILG cannot significantly suppress the inflammation due to the mutation of Cys-46 in the transgenic mice. Collectively, our findings indicate that the ILG inhibited T cell activation in vivo and in vitro via directly binding to IKK? Cys46.
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