Cell‐ and Tissue‐Based Proteome Profiling and Dual Imaging of Apoptosis Markers with Probes Derived from Venetoclax and Idasanutlin |
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| Authors: | Yun Ni Prof. Lin Li Prof. Zhi‐Min Zhang Prof. Piliang Hao Prof. Yong Xu Prof. Ke Ding Prof. Zhengqiu Li |
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| Affiliation: | 1. Institute of Advanced Materials (IAM), Nanjing Tech University, China;2. School of Pharmacy, Jinan University, Guangzhou City Key, Laboratory of Precision Chemical Drug Development, International Cooperative Laboratory of Traditional Chinese, Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of People's Republic of China, Guangzhou, China;3. School of Life Science and Technology, ShanghaiTech University, China;4. Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;5. University of Chinese Academy of Sciences, Beijing, China |
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| Abstract: | Venetoclax (ABT‐199) and idasanutlin (RG7388) are efficient anticancer drugs targeting two essential apoptosis markers, Bcl‐2 and MDM2, respectively. Recent studies have shown that the combination of these two drugs leads to remarkable enhancement of anticancer efficacy, both in vitro and in vivo. In an attempt to disclose the relationships of their protein targets, competitive affinity‐based proteome profiling coupled with bioimaging was employed to characterize their protein targets in the same cancer cell line and tumor tissue. A series of protein hits, including ITPR1, GSR, RER1, PDIA3, Apoa1, and Tnfrsf17 were simultaneously identified by pull‐down/LC–MS/MS with the two sets of affinity‐based probes. Dual imaging was successfully carried out, with the simultaneous detection of Bcl‐2 and MDM2 expression in various cancer cells. This could facilitate the novel diagnostic and therapeutic strategies of dual targeting of Bcl‐2/MDM2. |
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| Keywords: | affinity-based probes antitumor agents apoptosis biomarkers combination drugs target identification |
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