HIF-1 inhibitor-1

N-(2-Fluorophenethyl)-5-(2-methoxyphenyl)picolinamide is an inhibitor of hypoxia-inducible factor (HIF-1) signaling (IC₅₀ = 0.32 μM in a cell-based hypoxia responsive element (HRE) reporter assay under hypoxic conditions).¹ It inhibits hypoxia-induced increases in HIF-1α levels in MDA-MB-231, SKOV3, and HeLa cells in a concentration-dependent manner. N-(2-Fluorophenethyl)-5-(2-methoxyphenyl)picolinamide also inhibits hypoxia-induced VEGF expression and capillary-like tube formation in human umbilical vein endothelial cells (HUVECs) and inhibits migration and invasion of MDA-MB-231 cells in wound healing and transwell assays under hypoxic conditions. It also reduces lung metastasis in an MDA-MB-231 mouse xenograft model when administered at doses of 15 and 30 mg/kg every other day.

1.Liu, M., Liang, Y., Zhu, Z., et al.Discovery of novel aryl carboxamide derivatives as hypoxia-inducible factor 1α signaling inhibitors with potent activities of anticancer metastasisJ. Med. Chem.62(20)9299-9314(2019)