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SYP-5 is a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis.

SYP-5 inhibits hypoxia-induced upregulation of HIF-1. SYP-5 inhibits HIF-1 and downstream gene expression in Hep3B and Bcap37 cells. SYP-5 inhibits tumor cell migration and invasion, as well as tumor angiogenesis, which are mediated by suppressing PI3K/AKT- and MAPK/ERK-dependent HIF-1 pathway. The proteins of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 that are targets of HIF-1, are down-regulated by SYP-5. SYP-5 displays significant inhibition on hypoxia-induced overexpression of VEGF and MMP2 in both cell lines. In the tube formation assay, SYP-5 suppresses angiogenesis induced by hypoxia and VEGF in vitro. SYP-5 also retards the Hep3B and Bcap37 cells migration and invasion induced by hypoxia and FBS. SYP-5 specifically inhibits hypoxic induction of luciferase expression in U251-HRE but not in U251-pGL3[1].

[1]. Wang LH, et al. SYP-5, a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis. Eur J Pharmacol. 2016 Nov 15;791:560-568.

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