Binding characterization, synthesis and biological evaluation of RXRα antagonists targeting the coactivator binding
Dingyu Xu1, Shangjie Guo1, Ziwen Chen1
1School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, China.
Abstract:
Previously we identified the first retinoid X receptor-alpha (RXRα) modulators that regulate the RXRα biological function via binding to the coregulator-binding site. Here we report the characterization of the interactions between the hit molecule and RXRα through computational modeling, mutagenesis, SAR and biological evaluation. In addition, we reported studies of additional new compounds and identified a molecule that mediated the NF-κB pathway by inhibiting the TNFα-induced IκBα degradation and p65 nuclear translocation.
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