Optimization of a series of novel, potent and selective Macrocyclic SYK inhibitors.
Bioorg Med Chem Lett
; 91: 129352, 2023 07 15.
Article
en En
| MEDLINE
| ID: mdl-37270074
ABSTRACT
Spleen tyrosine kinase (SYK) is a non-receptor cytoplasmic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signalling, inhibition of SYK has been a target of interest in a variety of diseases. Herein, we report the use of structure-based drug design to discover a series of potent macrocyclic inhibitors of SYK, with excellent kinome selectivity and in vitro metabolic stability. We were able to remove hERG inhibition through the optimization of physical properties, and utilized a pro-drug strategy to address permeability challenges.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Transducción de Señal
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article