A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway

新型磷酰胺化合物 DCZ0805 通过 NF-κB 通路表现出强效抗骨髓瘤活性

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作者:Xuejie Gao #, Bo Li #, Anqi Ye #, Houcai Wang, Yongsheng Xie, Dandan Yu, Zhijian Xu, Bingqing Shi, Hui Zhang, Qilin Feng, Ke Hu, Yong Zhang, Cheng Huang, Guang Yang, Jumei Shi, Weiliang Zhu

Background

Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity.

Conclusion

The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

Methods

We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro.

Results

The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed.

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