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- W4382011856 abstract "Discovery of small molecule inhibitors targeting Mcl-1 (Myeloid cell leukemia 1) confronts many challenges. Based on the fact that Mcl-1 is mainly localized in mitochondria, we propose a new strategy of targeting mitochondria to improve the binding efficiency of Mcl-1 inhibitors. We report the discovery of complex 9, the first mitochondrial targeting platinum-based inhibitor of Mcl-1, which selectively binds to Mcl-1 with high binding affinity. Complex 9 was mainly concentrated in the mitochondria of tumor cells which led to an enhanced antitumor efficacy. Complex 9 induced Bax/Bak-dependent apoptosis in LP-1 cells and synergized with ABT-199 to kill ABT-199 resistant cells in multiple cancer models. Complex 9 was effective and tolerable as a single agent or in combination with ABT-199 in mouse models. This research work demonstrated that developing mitochondria-targeting Mcl-1 inhibitors is a new potentially efficient strategy for tumor therapy." @default.
- W4382011856 created "2023-06-27" @default.
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- W4382011856 date "2023-06-26" @default.
- W4382011856 modified "2023-10-08" @default.
- W4382011856 title "Platinum-Based Mcl-1 Inhibitor Targeting Mitochondria Achieves Enhanced Antitumor Activity as a Single Agent or in Combination with ABT-199" @default.
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- W4382011856 doi "https://doi.org/10.1021/acs.jmedchem.3c00355" @default.
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