A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth / 药学学报
Acta Pharmaceutica Sinica
;
(12): 622-6, 2014.
Article
in Chinese
| WPRIM
| ID: wpr-448629
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2014
Type:
Article
Similar
MEDLINE
...
LILACS
LIS