中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/β-catenin signaling inhibitors to suppress colorectal cancer

文献类型：期刊论文

作者Zhou, Jianhui5,6; Xu, Beibei3,4; Shen, Qianwen4; Zhang, Zhenwei2,5; Hu, Yuting5,6; Wang, Mengxue5,6; Su, Yongcheng4; Lei, Ziyu4; Zhang, Wenqing4; Liu, Tao5
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-10-05
卷号276页码:16
关键词Key & Oslash Colorectal cancer Wnt/ beta-catenin Hsp90 Tetrahydroisoquinoline rds
ISSN号0223-5234
DOI10.1016/j.ejmech.2024.116664
通讯作者Liu, Hong(hliu@simm.ac.cn) ; Hu, Tianhui(thu@xmu.edu.cn) ; Zhou, Yu(zhouyu@simm.ac.cn)
英文摘要Colorectal cancer (CRC) has been becoming one of the most common causes of cancer mortality worldwide. Accumulating studies suggest that the progressive up-regulation of Wnt/beta-catenin signaling is a crucial hallmark of CRC, and suppressing it is a promising strategy to treat CRC. Herein, we reported our latest efforts in the discovery of novel fused tetrahydroisoquinoline derivatives with good anti-CRC activities by screening our inhouse berberine-like library and further structure-activity relationship (SAR) studies, in which we identified compound 10 is a potent lead compound with significant antiproliferation potencies. By the biotinylated probe and LC-MS/MS study, Hsp90 was identified as its molecular target, which is a fully different mechanism of action from what we reported before. Further studies showed compound 10 directly engaged the N-terminal site of Hsp90 and promoted the degradation of beta-catenin, thereby suppressing the Wnt/beta-catenin signaling. More importantly, compound 10 exhibits favorable pharmacokinetic parameters and significant anti-tumor efficacies in the HCT116 xenograft model. Taken together, this study furnished the discovery of candidate drug compound 10 possessing a novel fused tetrahydroisoquinoline scaffold with excellent in vitro and in vivo anti-CRC activities by targeting Hsp90 to disturb Wnt/beta-catenin signaling pathway, which lay a foundation for discovering more effective CRC-targeted therapies.
WOS关键词BETA-CATENIN ; PATHWAY ; CASCADE ; HSP90
资助项目National Natural Science Foundation of China[21977106] ; National Natural Science Foundation of China[82173656] ; National Natural Science Foundation of China[82204424] ; Shenzhen Science and Technology Program[JCY20220530143406015] ; Natural Foundation of Fujian Province[2021R1001003] ; China Postdoctoral Science Foundation[2023M730821]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001273257800001
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/312556]  
专题中国科学院上海药物研究所
通讯作者Liu, Hong; Hu, Tianhui; Zhou, Yu
作者单位1.Xiamen Univ, Shenzhen Res Inst, Shenzhen 518057, Peoples R China
2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
3.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol, Shenzhen 518055, Peoples R China
4.Xiamen Univ, Canc Res Ctr, Xiamen Key Lab Tumor Metastasis, Sch Med, Xiamen 361102, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Dev Ctr, Shanghai 201203, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Jianhui,Xu, Beibei,Shen, Qianwen,et al. Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/β-catenin signaling inhibitors to suppress colorectal cancer[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2024,276:16.
APA Zhou, Jianhui.,Xu, Beibei.,Shen, Qianwen.,Zhang, Zhenwei.,Hu, Yuting.,...&Zhou, Yu.(2024).Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/β-catenin signaling inhibitors to suppress colorectal cancer.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,276,16.
MLA Zhou, Jianhui,et al."Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/β-catenin signaling inhibitors to suppress colorectal cancer".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 276(2024):16.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。