A high-throughput cell-based screening for L858R/T790M mutant epidermal growth factor receptor inhibitors.
Anticancer Res
; 32(1): 147-51, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-22213300
ABSTRACT
A high-throughput 32D(L858R/T790M) cell-based assay to identify inhibitors of the L858R/T790M mutant epidermal growth factor receptor (EGFR) pathway was established. After screening, ten hits from among 60,000 compounds in our in-house compound library were initially identified. In the secondary assays, one hit, 1-[2-(decyloxy)-2-oxoethyl]-3-methyl-2-[(4-methylphenoxy) methyl]-1H-benzimidazol-3-ium, was confirmed to directly inhibit the kinase activity of recombinant L858R/T790M EGFR and the phosphorylation of EGFR-L858R/T790M in gefitinib-resistant H1975 cells. Thus, this high-throughput assay system may be useful for identifying novel inhibitors which suppress mutant EGFR-T790M signalling and for overcoming T790M-mediated acquired resistance for future anticancer drug discovery.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Carcinoma Pulmonar de Células não Pequenas
/
Fator de Crescimento Epidérmico
/
Receptores ErbB
/
Neoplasias Pulmonares
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2012
Tipo de documento:
Article