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G. To evaluate effects of IKBKE/TBK1 inhibition on NF- B signaling in Ewing, TC32 cells were incubated with CYT387 for six hours prior to stimulation with TNF- (30 ng/mL). I B degradation was measured by harvesting TC32 cells thirty minutes after stimulation with TNF- . TNF- stimulation resulted in degradation of I B , and this effect was attenuated with CYT387 treatment. Parthenolide, an inhibitor of I B phosphorylation was used as a positive control. Similar effects of CYT387 activity were seen in HEK-293T cells which also express IKBKΕ. Nuclear extracts were prepared from TC32 cells harvested following forty-five minutes of TNF- stimulation. Treatment with CYT387 resulted in decreased nuclear localization of NF- B family proteins RelA/p65 and c-Rel. There was a modest impairment of p50 nuclear localization as compared to parthenolide and DMSO controls and no change in p52 nuclear localization. RelB (not shown) is not expressed in TC32 cells
CBL0137 (CBLC137, Curaxin 137) HCl激活p53并抑制NF-kB,在细胞实验中,IC50分别为0.37 μM 和 0.47 μM。它还能抑制组蛋白分子伴侣FACT,FACT促进染色质转录...NF
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