Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer--广州生物医药与健康研究院2024

论文

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

Qiuping Xiang, Chao Wang, Tianbang Wu, Cheng Zhang, Qingqing Hu, Guolong Luo, Jiankang Hu , Xiaoxi Zhuang, Lingjiao Zou , Hui Shen, Xishan Wu , Yan Zhang , Xiangqian Kong, Jinsong Liu, Yong Xu
论文出处
刊物名称

Journal of Medicinal Chemistry
年卷期页

2022, 65, 1, 785-810
联系作者

Yong Xu
影响因子

8.039
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
外单位作者单位
备注