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ShanghaiTech University Knowledge Management System
| Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors | |
| 2024-11-01 | |
| 发表期刊 | ARCHIV DER PHARMAZIE (IF:4.3[JCR-2023],4.4[5-Year]) |
| ISSN | 0365-6233 |
| EISSN | 1521-4184 |
| 发表状态 | 已发表 |
| DOI | 10.1002/ardp.202400594 |
| 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. |
| 关键词 | inhibitor pharmacokinetic study pyridazin-4-one receptor-interacting protein kinase 1 selectivity |
| URL | 查看原文 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | Natural Science Foundation of China for Innovation Research Group[81821005] ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] ; Shandong Laboratory Program[SYS202205] ; null[2022YFE0203600] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| WOS类目 | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| WOS记录号 | WOS:001360403500001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/452374 |
| 专题 | 生命科学与技术学院 生命科学与技术学院_特聘教授组_耿美玉组 生命科学与技术学院_硕士生 |
| 通讯作者 | Ai, Jing; Zhang, Hefeng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Small Mol Drug Res Ctr, 555 ZuChong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Canc Res Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.China Pharmaceut Univ, Dept Med Chem, State Key Lab Nat Med, Nanjing, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China 7.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, 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. |
| 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. |
| MLA | An, Yuxiang,et al."Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors".ARCHIV DER PHARMAZIE (2024). |
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