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 thieno[2,3-b]quinoline-procaine hybrid molecules: A new class of allosteric SHP-1 activators evolved from PTP1B inhibitors

文献类型：期刊论文

作者Xu, Lei1,2,3; Xuyan, Xuyang1,4; Minmi, Minmin1,2; Wang, Zhiji1,2; Shee, Chao5; Mu, Qianwen2; Feng, Bo2; Xu, Yechun2; Hou, Tingjun5; Gao, Lixin1,2
刊名CHINESE CHEMICAL LETTERS
出版日期2023-08-01
卷号34期号:8页码:6
ISSN号1001-8417
关键词Activator PTPs Inhibitor Thieno[2 b ]quinoline derivatives Diffuse large B-cell lymphoma
DOI10.1016/j.cclet.2022.108063
通讯作者Li, Jia(jli@simm.ac.cn) ; Zhou, Yubo(ybzhou@simm.ac.cn) ; Wang, Wenlong(wenlongwang@jiangnan.edu.cn)
英文摘要Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction. However, targeted protein activation is chemically challenging. Developing activators against Src homology region 2 domain-containing phosphatase-1 (SHP-1) to block STAT3 pathway represents a promising strategy for DLBCL therapy. Here we reported a new class of thieno[2,3- b ]quinolineprocaine hybrid molecules as SHP-1 allosteric activators. The representative hybrid compound 3b displayed SHP-1 activating effect with EC 50 of 5.48 & PLUSMN; 0.28 & mu;mol/L. Further investigations confirmed that 3b allosterically interacted with SHP-1, switched it from close to open conformation, blocked SHP-1/ p STAT3 pathway, induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro , and delayed tumor growth in the xenograft model of SU-DHL-2. Overall, this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors, and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway.& COPY; 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
WOS关键词PROTEIN-TYROSINE-PHOSPHATASE ; HEPATOCELLULAR-CARCINOMA CELLS ; BIOLOGICAL EVALUATION ; DRUG TARGET ; SORAFENIB ; APOPTOSIS ; DERIVATIVES ; MECHANISMS ; DISCOVERY ; AGONIST
资助项目National Natural Science Founda- tion of China[81773779] ; National Natural Science Founda- tion of China[21772068] ; National Natural Science Founda- tion of China[22277043] ; National Science amp; Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX097110 02-0 07-1] ; Nat- ural Science Foundation of Jiangsu Province[BK20190608] ; Postgraduate Research amp; Practice Innovation Program of Jiangsu Province[KYCX22_2330]
WOS研究方向Chemistry
语种英语
出版者ELSEVIER SCIENCE INC
WOS记录号WOS:001024268300001
源URL[http://119.78.100.183/handle/2S10ELR8/306451]  
专题新药研究国家重点实验室
通讯作者Li, Jia; Zhou, Yubo; Wang, Wenlong
作者单位1.Jiangnan Univ, Sch Life Sci & Hlth Engn, Wuxi 214122, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Jiangnan Univ, Sch Chem & Mat Engn, Wuxi 214122, Peoples R China
5.Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Lei,Xuyan, Xuyang,Minmi, Minmin,et al. Novel thieno[2,3-b]quinoline-procaine hybrid molecules: A new class of allosteric SHP-1 activators evolved from PTP1B inhibitors[J]. CHINESE CHEMICAL LETTERS,2023,34(8):6.
APA Xu, Lei.,Xuyan, Xuyang.,Minmi, Minmin.,Wang, Zhiji.,Shee, Chao.,...&Wang, Wenlong.(2023).Novel thieno[2,3-b]quinoline-procaine hybrid molecules: A new class of allosteric SHP-1 activators evolved from PTP1B inhibitors.CHINESE CHEMICAL LETTERS,34(8),6.
MLA Xu, Lei,et al."Novel thieno[2,3-b]quinoline-procaine hybrid molecules: A new class of allosteric SHP-1 activators evolved from PTP1B inhibitors".CHINESE CHEMICAL LETTERS 34.8(2023):6.

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。