Discovery of 5-(1-benzyl-1H-imidazol-4-yl)-1,2,4-oxadiazole derivatives as novel RIPK1 inhibitors via structure-based virtual screening.
Drug Dev Res
; 85(5): e22235, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39021343
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxadiazoles
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Inhibidores de Proteínas Quinasas
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Proteína Serina-Treonina Quinasas de Interacción con Receptores
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Simulación de Dinámica Molecular
Límite:
Humans
Idioma:
En
Revista:
Drug Dev Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos