Design, synthesis, and biological evaluation of new B-RafV600E kinase inhibitors.
Bioorg Med Chem
; 26(9): 2372-2380, 2018 05 15.
Article
en En
| MEDLINE
| ID: mdl-29602674
ABSTRACT
The association of deregulated signal pathways with various diseases has long been a research hotspot. One of the most important signal pathways, the MAPK (mitogen-activated protein kinase) signal pathway, plays a vital role in transducing extracellular signals into vital intracellular mechanisms. While mutations on its key component Raf kinase lead to sever diseases, targeted inhibition has thereby become an attractive therapeutic strategy. Several drugs have been approved for the treatment of Raf relevant diseases, yet more candidates are ever needed as the known drugs have confronted resistance and side effects. In the present study, we primarily investigated the binding modes of type I/II and type II inhibitors with B-Raf kinase. Based on the current knowledge, these ligands were fragmented and recombined to provide new interesting insights. Afterwards, a series of derivatives has been synthesized after the validation of hit compound. In addition, in vitro assays were carried out to profile the pharmacological properties of all the entities. Of all the compounds, compound 5h showed the best profile and may be used in the future study.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Benzamidas
/
Proteínas Proto-Oncogénicas B-raf
/
Inhibidores de Proteínas Quinasas
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2018
Tipo del documento:
Article