Identification of a novel series of azabenzimidazole-derived inhibitors of spleen tyrosine kinase.
Bioorg Med Chem Lett
; 30(18): 127393, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32721854
ABSTRACT
Spleen Tyrosine Kinase (SYK) is a well-studied enzyme with therapeutic applications in oncology and autoimmune diseases. We identified an azabenzimidazole (ABI) series of SYK inhibitors by mining activity data of 86,000 compounds from legacy biochemical assays with SYK and other homologous kinases as target enzymes. A structure-based design and hybridization approach was then used to improve the potency and kinase selectivity of the hits. Lead compound 23 from this novel ABI series has a SYK IC50 = 0.21 nM in a biochemical assay and inhibits growth of SUDHL-4 cells at a GI50 = 210 nM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Compuestos Aza
/
Bencimidazoles
/
Inhibidores de Proteínas Quinasas
/
Quinasa Syk
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos