通过基于结构的虚拟筛选发现 5-(1-苄基-1H-咪唑-4-基)-1,2,4-恶二唑衍生物作为新型 RIPK1 抑制剂。

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2024-07-18 DOI:10.1002/ddr.22235

Yanzhen Yu, Yunzhen Hu, Huihui Yan, Xin Zeng, Haodong Yang, Lei Xu, Rong Sheng

{"title":"通过基于结构的虚拟筛选发现 5-(1-苄基-1H-咪唑-4-基)-1,2,4-恶二唑衍生物作为新型 RIPK1 抑制剂。","authors":"Yanzhen Yu, Yunzhen Hu, Huihui Yan, Xin Zeng, Haodong Yang, Lei Xu, Rong Sheng","doi":"10.1002/ddr.22235","DOIUrl":null,"url":null,"abstract":"RIPK1 plays a key role in necroptosis and is associated with various inflammatory diseases. Using structure-based virtual screening, a novel hit with 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole scaffold was identified as an RIPK1 inhibitor with an IC50 value of 1.3 μM. Further structure–activity relationship study was performed based on similarity research and biological evaluation. The molecular dynamics simulation of compound 2 with RIPK1 indicated that it may act as a type II kinase inhibitor. This study provides a highly efficient way to discover novel scaffold RIPK1 inhibitors for further development.","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"85 5","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery of 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole derivatives as novel RIPK1 inhibitors via structure-based virtual screening\",\"authors\":\"Yanzhen Yu, Yunzhen Hu, Huihui Yan, Xin Zeng, Haodong Yang, Lei Xu, Rong Sheng\",\"doi\":\"10.1002/ddr.22235\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"RIPK1 plays a key role in necroptosis and is associated with various inflammatory diseases. Using structure-based virtual screening, a novel hit with 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole scaffold was identified as an RIPK1 inhibitor with an IC50 value of 1.3 μM. Further structure–activity relationship study was performed based on similarity research and biological evaluation. The molecular dynamics simulation of compound 2 with RIPK1 indicated that it may act as a type II kinase inhibitor. This study provides a highly efficient way to discover novel scaffold RIPK1 inhibitors for further development.\",\"PeriodicalId\":11291,\"journal\":{\"name\":\"Drug Development Research\",\"volume\":\"85 5\",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Development Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22235\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22235","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

摘要

RIPK1 在坏死过程中起着关键作用，并与多种炎症疾病相关。通过基于结构的虚拟筛选，一个具有 5-(1-苄基-1H-咪唑-4-基)-1,2,4-恶二唑支架的新发现被鉴定为 RIPK1 抑制剂，其 IC50 值为 1.3 μM。在相似性研究和生物学评价的基础上，进行了进一步的结构-活性关系研究。化合物 2 与 RIPK1 的分子动力学模拟表明，它可能是一种 II 型激酶抑制剂。这项研究为发现新型支架 RIPK1 抑制剂提供了一种高效的方法，有助于进一步开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Discovery of 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole derivatives as novel RIPK1 inhibitors via structure-based virtual screening

RIPK1 plays a key role in necroptosis and is associated with various inflammatory diseases. Using structure-based virtual screening, a novel hit with 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole scaffold was identified as an RIPK1 inhibitor with an IC₅₀ value of 1.3 μM. Further structure–activity relationship study was performed based on similarity research and biological evaluation. The molecular dynamics simulation of compound 2 with RIPK1 indicated that it may act as a type II kinase inhibitor. This study provides a highly efficient way to discover novel scaffold RIPK1 inhibitors for further development.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.