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
Discovery of 1,5-Dihydro-4H-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2

文献类型：期刊论文

作者Che, Jinxin1; Wang, Zhilong2; Shen, Zheyuan1; Zhuang, Weihao1; Ying, Huazhou1; Hu, Yongzhou1; Hu, Youhong3,4; Xie, Xin2,4; Dong, Xiaowu1,5,6
刊名ACS MEDICINAL CHEMISTRY LETTERS
出版日期2021-05-13
卷号12期号:5页码:836-845
关键词cancer metastasis CXCR1 CXCR2 selectivity antagonist 1,5-dihydro-4H-imidazol-4-one
ISSN号1948-5875
DOI10.1021/acsmedchemlett.1c00113
通讯作者Hu, Youhong(yhhu@simm.ac.cn) ; Xie, Xin(xxie@simm.ac.cn) ; Dong, Xiaowu(dongxw@zju.edu.cn)
英文摘要CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound 2 bearing a 1,5-dihydro-4H-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism preference. Further optimization and structure-activity relationship studies led to compound C5 that overcame the disadvantages of compound 2 and performed with higher selectivity. It showed excellent oral bioavailability and in vitro anticancer metastasis activity. Further dynamic simulation of the molecular protein complex showed that the amino acid residue K320 of CXCR2 contributed most to the selectivity of C5. This study provides important clues for the design of new CXCR2 selective antagonists, and C5 can be a molecular tool for investigating the difference in the biological function of CXCR1 and CXCR2.
WOS关键词OPTIMIZATION ; CANCER ; SERIES
资助项目National Natural Science Foundation of China[81973172] ; National Natural Science Foundation of China[82003579] ; China Postdoctoral Science Foundation[2019M652123] ; Zhejiang Provincial Natural Science Foundation of China[LR21H300003] ; Zhejiang Provincial Natural Science Foundation of China[LQ21H300005]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000651790900024
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/297249]  
专题新药研究国家重点实验室
通讯作者Hu, Youhong; Xie, Xin; Dong, Xiaowu
作者单位1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou Inst Innovat Med, Hangzhou 310058, Peoples R China
2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Laborarory Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310058, Peoples R China
5.ZhejiangUniv, Innovat Inst Artificial Intelligence Med, Hangzhou 310018, Peoples R China
6.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China
推荐引用方式
GB/T 7714		 Che, Jinxin,Wang, Zhilong,Shen, Zheyuan,et al. Discovery of 1,5-Dihydro-4H-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2[J]. ACS MEDICINAL CHEMISTRY LETTERS,2021,12(5):836-845.
APA Che, Jinxin.,Wang, Zhilong.,Shen, Zheyuan.,Zhuang, Weihao.,Ying, Huazhou.,...&Dong, Xiaowu.(2021).Discovery of 1,5-Dihydro-4H-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2.ACS MEDICINAL CHEMISTRY LETTERS,12(5),836-845.
MLA Che, Jinxin,et al."Discovery of 1,5-Dihydro-4H-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2".ACS MEDICINAL CHEMISTRY LETTERS 12.5(2021):836-845.

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。