Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton's Tyrosine Kinase.
J Med Chem
; 58(14): 5437-44, 2015 Jul 23.
Article
en En
| MEDLINE
| ID: mdl-26087137
ABSTRACT
The discovery and optimization of a series of 4-aminocinnoline-3-carboxamide inhibitors of Bruton's tyrosine kinase are reported. A fragment-based screening approach incorporating X-ray co-crystallography was used to identify a cinnoline fragment and characterize its binding mode in the ATP binding site of Btk. Optimization of the fragment hit resulted in the identification of a lead compound which reduced paw swelling in a dose- and exposure-dependent fashion in a rat model of collagen-induced arthritis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Inhibidores de Proteínas Quinasas
/
Bibliotecas de Moléculas Pequeñas
/
Descubrimiento de Drogas
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos