Pharmacological activation of the p53 pathway by a new compound CYZ2017 exerts anti-tumor effects
Yuqiao Han, Ziwei Ren, Yixin Wu, Yunzhong Chen, Zhenmei Cui, Tong Zhu, Mingliang Ma, Yijie Du, Suzhen Dong
Journal：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
IF：2.99
DOI：10.1016/j.bbrc.2020.09.122
PMID：
Published：2020-10-02
research field：肿瘤学分子生物学药理学生物化学
Abstract
Blockage of p53-MDM2 protein-protein interaction has long been a promising strategy of drug development for cancers with wild type p53. In this study, we report a new p53-MDM2 interaction inhibitor, CYZ2017, which could induce p53 nuclear translocation and possess p53-dependent anti-proliferation activity in a range of cancer cells. CYZ2017 treatment led to increase of p53 levels and induced the transactivation of its target genes p21. In addition, CYZ2017 induced G0/G1 cell cycle arrest and apoptosis in HCT116 cells. Besides, CYZ2017 suppressed tumor growth in a HCT116 xenograft model without visible toxicity. These results support that CYZ2017 might be a promising p53-MDM2 interaction inhibitor with good anti-tumor activity. Our finding provides some cues for further investigation of developing anti-tumor drugs based on the blockage of p53-MDM2 interaction.
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