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

Autor: Yu Y; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Hu Y; Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yan H; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Zeng X; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China., Yang H; Jinhua Institute of Zhejiang University, Zhejiang University, Jinhua, China., Xu L; Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, China., Sheng R; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Jinhua Institute of Zhejiang University, Zhejiang University, Jinhua, China.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2024 Aug; Vol. 85 (5), pp. e22235.
DOI: 10.1002/ddr.22235
Abstrakt: 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 IC 50 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.
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Databáze: MEDLINE
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