| 论文编号: |
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| 第一作者所在部门: |
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| 中文论文题目: |
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer |
| 英文论文题目: |
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer |
| 作者: |
Xiang Q, Wang C, Wu T, Zhang C, Hu Q, Luo G, Hu J, Zhuang X, Zou L, Shen H, Wu X, Zhang Y, Kong X, Liu J, Xu Y |
| 论文出处: |
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| 刊物名称: |
Journal of Medicinal Chemistry |
| 年: |
2022 |
| 卷: |
65 |
| 期: |
1 |
| 页: |
785-810 |
| 联系作者: |
Yong Xu |
| 收录类别: |
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| 影响因子: |
11.049 |
| 摘要: |
CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) is a potential target for prostate cancer treatment. Herein, we report the structural optimization of a series of 1-(indolizin-3-yl)ethan-1-one compounds as new selective CBP bromodomain inhibitors, aiming to improve cellular potency and metabolic stability. This process led to compound 9g (Y08284), which possesses good liver microsomal stability and pharmacokinetic properties (F = 25.9%). Furthermore, the compound is able to inhibit CBP bromodomain as well as the proliferation, colony formation, and migration of prostate cancer cells. Additionally, the new inhibitor shows promising antitumor efficacy in a 22Rv1 xenograft model (TGI = 88%). This study provides new lead compounds for further development of drugs for the treatment of prostate cancer. |
| 英文摘要: |
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