| 論文編號: |
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| 第一作者所在部門: |
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| 中文論文題目: |
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer |
| 英文論文題目: |
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 |
| 論文出處: |
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| 刊物名稱: |
Journal of Medicinal Chemistry |
| 年: |
2022 |
| 卷: |
65 |
| 期: |
1 |
| 頁: |
785-810 |
| 聯係作者: |
Yong Xu |
| 收錄類別: |
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| 影響因子: |
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 compound9g(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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| 外單位作者單位: |
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