title: [A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth].
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.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Lai
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Niu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lang
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D008819:Mice, Nude
chemical_list: D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D017705:Lignans; C054895:manassantin A