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
  4. 新药研究国家重点实验室
Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer

文献类型：期刊论文

作者Zhang, Shurui5,6; Chen, Xiaoxu3,4,5; Wu, Chenglin5; Xu, Hui3,5; Xie, Xiong3,5; Feng, Mingshun3,4,5; Hu, Shulei5,6; Bai, Hudagula3,5; Gao, Feng3,5; Tong, Linjiang3,5
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-06-09
卷号65期号:11页码:7697-7716
ISSN号0022-2623
DOI10.1021/acs.jmedchem.2c00040
通讯作者Liu, Hong(hliu@simm.ac.cn) ; Xie, Zuoquan(zqxie@simm.ac.cn) ; Wang, Jiang(154141903@qq.com)
英文摘要Targeting sphingosine kinase 1 (SphK1) has become a novel strategy for the treatment of inflammatory bowel disease and cancer via the SphK1/S1P signaling pathway. However, exploration of SphK1 inhibitor therapeutic applications has been hampered by the poor pharmacokinetic properties of these SphK1 inhibitors. Herein, we report the structural optimization and structure-activity relationship studies of a series of novel SphK1 inhibitors. The novel compound 28 selectively inhibits SphK1 and exhibits higher anti-proliferative activity compared to the positive compound PF-543 in various cancer cells, which is associated with the induction of G0/G1 phase arrest and apoptosis; besides, it could also inhibit the cell migration. Further, compound 28 can suppress in vivo growth of both colon tumor and triple-negative breast tumor and inhibits the lung metastasis of triple-negative breast cancer with higher potency compared with that of PF-543. Collectively, compound 28 represents a promising lead compound for the treatment of solid tumor and the metastasis.
WOS关键词DISCOVERY ; SPHINGOSINE-1-PHOSPHATE ; 1-PHOSPHATE ; DISEASE ; DESIGN ; POTENT ; SPHK
资助项目National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[21877118] ; National Natural Science Foundation of China[81620108027] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Science and Technology Commission of Shanghai Municipality[19431908100] ; Personalized Medicine-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020341] ; Shanghai Pujiang Program[18PJD052] ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000810271500001
源URL[http://119.78.100.183/handle/2S10ELR8/301545]  
专题新药研究国家重点实验室
通讯作者Liu, Hong; Xie, Zuoquan; Wang, Jiang
作者单位1.Lingang Lab, Shanghai 200031, Peoples R China
2.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.China Pharmaceut Univ, Nanjing 211198, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Shurui,Chen, Xiaoxu,Wu, Chenglin,et al. Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(11):7697-7716.
APA Zhang, Shurui.,Chen, Xiaoxu.,Wu, Chenglin.,Xu, Hui.,Xie, Xiong.,...&Wang, Jiang.(2022).Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer.JOURNAL OF MEDICINAL CHEMISTRY,65(11),7697-7716.
MLA Zhang, Shurui,et al."Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer".JOURNAL OF MEDICINAL CHEMISTRY 65.11(2022):7697-7716.

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。