Structural modification of an EGFR inhibitor that showed weak off-target activity against RET leading to the discovery of a potent RET inhibitor.
Mol Divers
; 18(2): 403-9, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24515340
ABSTRACT
Here, we describe the structural optimization of a known EGFR inhibitor (compound 1) that showed weak off-target activity against RET. Twenty-six analogs of 1 were synthesized. SAR analysis led to the discovery of several compounds that showed considerable potency against the RET-dependent thyroid cancer cell line TT. Kinase inhibitory potency was then measured for the most active compound (2u) in the cellular assay. The results showed that 2u is a potent RET inhibitor with an IC(50) value of 7 nM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteínas Quinases
/
Proteínas Proto-Oncogênicas c-ret
/
Descoberta de Drogas
/
Receptores ErbB
Limite:
Humans
Idioma:
En
Revista:
Mol Divers
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China