Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia.
Leuk Res
; 35(5): 677-81, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21145592
ABSTRACT
Aminopeptidase enzyme inhibition is thought to deplete the free intracellular amino acids needed by malignant cells for growth and development, resulting in profound anti-proliferative and apoptotic effects. In this study, we investigated the effects of the metalloenzyme-inhibitor CHR-2797 (tosedostat), in primary acute myeloid leukemia (AML) cells. CHR-2797 demonstrated marked in vitro cytotoxicity in AML samples and strong synergy with Cytarabine (Ara-C), but significantly less cytotoxicity to normal marrow progenitors. Furthermore mechanistic investigations revealed that CHR-2797 inhibited the intrinsic nuclear, cytoplasmic and cell surface aminopeptidase function of AML blasts in a dose-dependent manner, demonstrating a promising novel approach for AML therapy.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Leucemia
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Glicina
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Aminopeptidases
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Ácidos Hidroxâmicos
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido