Cell- and Tissue-Based Proteome Profiling and Dual Imaging of Apoptosis Markers with Probes Derived from Venetoclax and Idasanutlin

Angewandte Chemie
Dongsheng ZhuZhengqiu Li

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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Citations

Mar 1, 2019·Organic & Biomolecular Chemistry·Wenjie LangJingyan Ge
Apr 4, 2019·Chembiochem : a European Journal of Chemical Biology·Yu ChangZhengqiu Li
Nov 26, 2019·Chemistry, an Asian Journal·Jiaqian XuZhengqiu Li
Sep 4, 2020·Chembiochem : a European Journal of Chemical Biology·Xiaodong ZhangZhichao Zhang
Dec 29, 2020·Cell Chemical Biology·Jaeyoung HaSeung Bum Park
Mar 12, 2020·Journal of the American Chemical Society·Nan MaZhengqiu Li
Aug 14, 2021·Acta Pharmaceutica Sinica. B·Chenglong GaoTao Pang
Apr 16, 2020·ACS Medicinal Chemistry Letters·Jiaqian XuZhengqiu Li
Sep 16, 2021·Molecular Pharmaceutics·Zhengyuan ZhouSatish K Chitneni

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