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• W4296311335 endingPage "106156" @default.
• W4296311335 startingPage "106156" @default.
• W4296311335 abstract "Nur77, an orphan nuclear receptor, is implicated in regulating diverse cellular biological processes including apoptosis and inflammation. We previously identified BI1071 (DIM-C-pPhCF3+MeSO3-), an oxidized methanesulfonate salt of (4-CF3-Ph-C-DIM), was a direct ligand of Nur77, which could activate the Nur77-Bcl-2 apoptotic pathway. To obtain more effective compounds targeting the Nur77-mediated apoptotic pathway, we designed and synthesized a series of BI1071 analogs by introducing various substituent groups in the indolyl-rings of BI1071. Structure-activity relationship study identified A11, B5 and B15 as improved analogs with stronger binding affinity to Nur77 and enhanced apoptotic activity compared to BI1071. Nur77-binding studies demonstrated that A11, B5 and B15 bind to Nur77 with a Kd of 34 nM, 19 nM and 16 nM, respectively. Furthermore, mechanism studies showed that A11, B5 and B15 induced apoptosis through utilizing the Nur77-Bcl-2 pathway." @default.
• W4296311335 created "2022-09-20" @default.
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• W4296311335 date "2022-12-01" @default.
• W4296311335 modified "2023-09-24" @default.
• W4296311335 title "SAR study of oxidative DIMs analogs targeting the Nur77-mediated apoptotic pathway of cancer cells" @default.
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• W4296311335 doi "https://doi.org/10.1016/j.bioorg.2022.106156" @default.
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