Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.
Bioorg Med Chem
; 26(3): 747-757, 2018 02 01.
Article
em En
| MEDLINE
| ID: mdl-29317150
ABSTRACT
Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34â¯nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9⯵M in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Receptor Tipo 1 de Fator de Crescimento de Fibroblastos
/
Inibidores de Histona Desacetilases
/
Desacetilase 6 de Histona
/
Indazóis
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China