| Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer |
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| 作者姓名： | Jia-Luo Huang Xue-Long Yan Dong Huang Lu Gan Huahua Gao Run-Zhu Fan Shen Li Fang-Yu Yuan Xinying Zhu Gui-Hua Tang Hong-Wu Chen Junjian Wang Sheng Yin |
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| 作者单位： | 1. School of Pharmaceutical Sciences, Sun Yat-sen University;2. School of Pharmacy, Guizhou Medical University;3. School of Medicine, University of California Davis |
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| 基金项目： | supported by the Natural Science Foundation of China (Nos. 82273804, 81973195, 81872891, and 81973203)；;the Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2019B151502016, China)；;Guangdong-Hong Kong-Macao research team project of the Guangdong Basic and Applied Basic Research Foundation (No. 2022B1515130008, China)； |
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| 摘 要： | Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability(>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer(CRPC) cells with sub-nanomolar potency and completely preven...
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