Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells.
Leuk Res
; 30(9): 1167-75, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16510182
ABSTRACT
The anti-epileptic drug valproic acid harbors anti-tumoral activity in solid and leukemic tumor cell models and is currently evaluated in clinical trials. However, the plasma trough concentrations obtained in patients by common anti-epileptic dose regimens are below concentrations required for exerting anti-tumor effects in vitro. Here, we describe the identification of three novel valproic acid derivatives with superior differentiation-inducing and anti-proliferative activities in K562 bcr/abl-positive chronic myeloid leukemia cells and HL60 promyelocytic leukemia cells at achievable therapeutic VPA concentrations. These compounds reveal potent inhibition of histone deacetylase activity, induction of p21Cip/Waf expression as well as low toxicity on CD34+ bone marrow cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide
/
Diferenciação Celular
/
Ácido Valproico
/
Anticonvulsivantes
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Alemanha