A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth / 药学学报
Acta Pharmaceutica Sinica
; (12): 622-626, 2014.
Article
en Zh
| WPRIM
| ID: wpr-245037
Biblioteca responsable:
WPRO
ABSTRACT
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Farmacología
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Neoplasias de la Mama
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Regulación Neoplásica de la Expresión Génica
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Lignanos
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Línea Celular Tumoral
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Factor 1 Inducible por Hipoxia
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Xenoinjertos
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Metabolismo
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Ratones Desnudos
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2014
Tipo del documento:
Article