The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants.
Oncogene
; 23(31): 5387-93, 2004 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-15064724
ABSTRACT
Point mutations constitute a major mode of oncogenic activation of the Met receptor tyrosine kinase. Met is aberrantly activated in many types of human malignancies and its deregulated activity is correlated with aggressive tumor traits such as abnormal proliferation and survival, leading to tumor growth, local invasion and metastasis. Here we report that the Met kinase inhibitor SU11274 differentially affects the kinase activity and subsequent signaling of various mutant forms of Met. Two Met variants tested, M1268T and H1112Y, were potently inhibited by 2 microM SU11274, while two other variants, L1213V and Y1248H, remained resistant under similar experimental conditions. Inhibition of the kinase altered cell proliferation, morphology and motility, while cells containing resistant mutants appeared unaffected by the compound. The basis for the sensitivity or resistance to SU11274 is discussed in terms of the position of the mutations predicted from a homology model.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Sulfonamidas
/
Proteínas Proto-Oncogênicas c-met
/
Inibidores Enzimáticos
/
Indóis
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Suíça