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MDM2 inhibitor APG-115 exerts potent antitumor activity and synergizes with standard-of-care agents in preclinical acute myeloid leukemia models

Cell Death Discov. 2021-05; 
Douglas D Fang, Qiuqiong Tang, Yanhui Kong, Tao Rong, Qixin Wang, Na Li, Xu Fang, Jiaxing Gu, Dengkun Xiong, Yan Yin, Jing Deng, Dajun Yang, Yifan Zhai
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Proteins, Expression, Isolation and Analysis Equal amounts of soluble protein were loaded and separated using 4–20% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (GenScript, Cat# M42010C) Get A Quote

摘要

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous clonal disease associated with unmet medical needs. Paralleling the pathology of other cancers, AML tumorigenesis and propagation can be ascribed to dysregulated cellular processes, including apoptosis. This function and others are regulated by tumor suppressor P53, which plays a pivotal role in leukemogenesis. Opposing P53-mediated activities is the mouse double minute 2 homolog (MDM2), which promotes P53 degradation. Because the TP53 mutation rate is low, and MDM2 frequently overexpressed, in patients with leukemia, targeting the MDM2-P53 axis to restore P53 function has emerged as an attractive AML treatment strategy. APG-115 is a pot... More

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