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 pyridazin-4-one derivatives as necroptosis inhibitors

文献类型：期刊论文

作者An, Yuxiang3,4; Peng, Xia2; Wang, Tianchen3,4; Liu, Kaiyuan1,2,3; Feng, Dazhi4,7; Fang, Chen4,6; Zhou, Xuan2,3,5; Geng, Meiyu1,2,3,8; Duan, Wenhu3,4,8; Ai, Jing2,3
刊名ARCHIV DER PHARMAZIE
出版日期2024-11-21
页码16
关键词inhibitor pharmacokinetic study pyridazin-4-one receptor-interacting protein kinase 1 selectivity
ISSN号0365-6233
DOI10.1002/ardp.202400594
通讯作者Ai, Jing(jai@simm.ac.cn) ; Zhang, Hefeng(zhanghefeng1@simm.ac.cn)
英文摘要Necroptosis is a regulated inflammatory cell death process that is closely associated with autoimmune diseases, acute ischemic injuries, neurodegenerative disorders, and so on. Due to the crucial role of receptor-interacting protein kinase 1 (RIPK1) in the necroptosis pathway, RIPK1 inhibitors are believed to have great potential in the treatment of necroptosis-related diseases. In this article, we reported a series of pyridazin-4-one derivatives as potent necroptosis inhibitors for both human and mouse cells. The representative compound 13 exhibited favorable RIPK1 selectivity and dose-dependently inhibited RIPK1 phosphorylation. The in vivo pharmacokinetic study indicated that compound 13 was an orally available candidate. Finally, molecular docking and molecular dynamics simulations were performed to elucidate the binding pattern of compound 13 with RIPK1. Collectively, compound 13 represents a promising lead compound for the future development of RIPK1-targeted necroptosis inhibitors.
WOS关键词RIPK1 ; INFLAMMATION
资助项目National Key R&D Program Strategic Scientific and Technological Innovation Cooperation Key Project ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] ; Shandong Laboratory Program[SYS202205] ; [2022YFE0203600]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:001360403500001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/314580]  
专题中国科学院上海药物研究所
通讯作者Ai, Jing; Zhang, Hefeng
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Canc Res Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Small Mol Drug Res Ctr, 555 ZuChong Zhi Rd, Shanghai 201203, Peoples R China
5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
7.China Pharmaceut Univ, Dept Med Chem, State Key Lab Nat Med, Nanjing, Peoples R China
8.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 An, Yuxiang,Peng, Xia,Wang, Tianchen,et al. Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors[J]. ARCHIV DER PHARMAZIE,2024:16.
APA An, Yuxiang.,Peng, Xia.,Wang, Tianchen.,Liu, Kaiyuan.,Feng, Dazhi.,...&Zhang, Hefeng.(2024).Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors.ARCHIV DER PHARMAZIE,16.
MLA An, Yuxiang,et al."Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors".ARCHIV DER PHARMAZIE (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。