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| 第一作者所在部门: |
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| 中文论文题目: |
Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1- ones as novel selective TRIM24/BRPF1 bromodomain inhibitors |
| 英文论文题目: |
Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1- ones as novel selective TRIM24/BRPF1 bromodomain inhibitors |
| 作者: |
Qiuping Xiang,Guolong Luo,Cheng Zhang,Qingqing Hua,Chao Wang,Tianbang Wu,c,Hongrui Xu,Jiankan gHu,Xiaoxi Zhuang,Maofeng Zhang,Shuang Wu,Jinxin Xu,YanZhang,Jinsong Liu,Yong Xu |
| 论文出处: |
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| 刊物名称: |
European Journal of Medicinal Chemistry |
| 年: |
2022 |
| 卷: |
236 |
| 期: |
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| 页: |
114311 |
| 联系作者: |
Yong Xu |
| 收录类别: |
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| 影响因子: |
7.088 |
| 摘要: |
TRIM24 (tripartite motif-containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are epigenetics "readers" and potential therapeutic targets for cancer and other diseases. Here we describe the structure-guided design of 1-(indolin-1-yl)ethan-1-ones as novel TRIM24/BRPF1 bromodomain inhibitors. The representative compound 20l (Y08624) is a new TRIM24/BRPF1 dual inhibitor, with IC50 values of 0.98 and 1.16 μM, respectively. Cellular activity of 20l was validated by viability assay in prostate cancer (PC) cell lines. In PC xenograft models, 20l suppressed tumor growth (50 mg/kg/day, TGI = 53%) without exhibiting noticeable toxicity. Compound 20l represents a versatile starting point for the development of more potent TRIM24/BRPF1 inhibitors. |
| 英文摘要: |
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