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 2.46×10-10 mol·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.
Original language | English (US) |
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Pages (from-to) | 622-626 |
Number of pages | 5 |
Journal | Yaoxue Xuebao |
Volume | 49 |
Issue number | 5 |
State | Published - May 12 2014 |
Externally published | Yes |
Keywords
- Antitumor
- Hypoxia-inducible factor-1
- Inhibitor
- Manassantin A derivative
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)