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- W4313443183 abstract "Combination of different molecular target inhibitors is an available method to improve the therapeutic effect on tumors. Herein, to achieve both tumor cell targeting and ALK degradation & CDK4/6 inhibition in one molecule, we designed and synthesized a novel GSH responsive Y-PROTACs, Y5-3, a highly potent molecule with an IC50 value of 90 nM against H3122 cells, which can be cleaved into ALK PROTAC and CDK4/6 inhibitor moieties in tumor cells. Mechanism studies revealed that Y5-3 exert anti-tumor proliferation activity in vitro not only by ALK degradation and CDK4/6 inhibition, but also by ALK/CDK4 dual degradation. These properties make Y5-3 a GSH responsive multifunctional antitumor agent, and our work provide a new strategy for the development of multifunctional PROTACs." @default.
- W4313443183 created "2023-01-06" @default.
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- W4313443183 date "2023-02-01" @default.
- W4313443183 modified "2023-10-17" @default.
- W4313443183 title "Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer" @default.
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- W4313443183 doi "https://doi.org/10.1016/j.ejmech.2022.115082" @default.
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