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• W2056508746 abstract "Broad spectrum Bcl-2 small molecule inhibitors act as BH3 mimetics are effective antitumor agents. Herein, we have identified S1, a previously discovered small molecule Bcl-2 inhibitor, as the first authentic BH3 mimetic as well as a dual, nanomolar inhibitor of Bcl-2 and Mcl-1 (Ki = 310 nM and 58 nM, respectively). The results of fluorescence polarization assays, coimmunoprecipitation, fluorescent resonance energy transfer, and shRNA indicated that S1 can disrupt Bcl-2/Bax, Mcl-1/Bak and Bcl-2/Bim heterodimerization in multiple cell lines, activate Bax accompanied by its translocation to mitochondrial, activate caspase 3 completely dependent on Bax/Bak, and in turn induce a Bim-independent apoptosis. Moreover, S1 could induce apoptosis on the primary acute lymphoblastic leukemia cells regardless of Mcl-1 level. Mechanism-based single agent antitumor activity in a mouse xenograft H22 (mouse liver carcinoma) model ascertain its therapeutic potential. S1 represents a novel chemical class of antitumor leads that function solely as BH3 mimetics and pan-Bcl-2 inhibitors. In the meanwhile, S1 could become a unique tool for interactions between Bcl-2 family proteins." @default.
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• W2056508746 date "2010-05-25" @default.
• W2056508746 modified "2023-10-17" @default.
• W2056508746 title "A novel BH3 mimetic S1 potently induces Bax/Bak-dependent apoptosis by targeting both Bcl-2 and Mcl-1" @default.
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• W2056508746 doi "https://doi.org/10.1002/ijc.25484" @default.
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