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
Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors

文献类型：期刊论文

作者Zhang, Junjie3,5; Li, Yan4; Tang, Haotian3,4; Zhou, Qianqian1,3,4; Tong, Linjiang4; Ding, Jian1,3,4; Xie, Hua2,3,4; Xiong, Bing3,5; Liu, Tongchao5
刊名BIOORGANIC CHEMISTRY
出版日期2023-11-01
卷号140页码:18
关键词Cancer immunotherapy HPK1 Structure -based design HPK1 inhibitor
ISSN号0045-2068
DOI10.1016/j.bioorg.2023.106811
通讯作者Xie, Hua(hxie@simm.ac.cn) ; Liu, Tongchao(tongchao_liu@simm.ac.cn)
英文摘要Despite immune checkpoint inhibitors' tremendous success in the treatment of tumors, the moderate response rate limits their widespread use. Hematopoietic progenitor kinase 1 (HPK1) is served as an essential negative regulator of T-cell receptor, which has been identified as a promising target for enhancing antitumor immunity. However, the development of a selective HPK1 inhibitor is still challenging. Herein, we reported a novel series of 1H-pyrazolo[3,4-d]pyrimidine derivatives as HPK1 inhibitors by structure-based rational design. The optimal compound 10n significantly inhibited HPK1 with an IC50 value of 29.0 nM and the phosphorylation of SLP76 at a concentration as low as 0.1 mu M. Furthermore, compound 10n exhibited good selectivity over a panel of 25 kinases, including GLK from the same MAP4K family. Together, the current study provided a novel, potent, and selective HPK1 inhibitor, acting as a lead compound for the future development of cancer immunotherapy.
WOS关键词DISCOVERY
资助项目National Natural Science Foundation of China[82173658] ; National Natural Science Foundation of China[81773572] ; National Natural Science Foundation of China[82273948] ; National Natural Science Foundation of China[82204187] ; high-level Innovative Research Institute[2021B0909050003]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:001077001000001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/307272]  
专题中国科学院上海药物研究所
通讯作者Xie, Hua; Liu, Tongchao
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Junjie,Li, Yan,Tang, Haotian,et al. Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors[J]. BIOORGANIC CHEMISTRY,2023,140:18.
APA Zhang, Junjie.,Li, Yan.,Tang, Haotian.,Zhou, Qianqian.,Tong, Linjiang.,...&Liu, Tongchao.(2023).Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors.BIOORGANIC CHEMISTRY,140,18.
MLA Zhang, Junjie,et al."Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors".BIOORGANIC CHEMISTRY 140(2023):18.

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。