Background:

KC7F2 is a novel inhibitor of HIF-1αwith IC50 value of 20 μM [1].

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor consisting of α and β subunits. In normal situation, the HIF-1α subunit is constitutively translated, but rapidly degraded. While, under hypoxia it is stabilized. HIF target genes encode a series of critical factors to adapt the low oxygen [1].

In a HIF-reporter cell line LN229-HRE-AP, KC7F2 (>25 μM) reduced AP activity by 90% in LN229 cells, which indicated that KC7F2 inhibited AP enzyme activity. In LNZ308 human glioma cells, KC7F2 inhibited the expression of a panel of HIF target genes, such as matrix metalloproteinase 2 (MMP2), enolase 1, carbonic anhydrase IX (CA IX) and endothelin 1. Also, KC7F2 reduced expression of HIF-1α in a dose-dependent way [1].

In a rat epilepsy model, KC7F2 significantly shortened the latent period in the PTZ kindling model and increased the rate of spontaneous recurrent seizures during the chronic stage in the lithium-pilocarpine model [3].

参考文献:
[1].  Narita T, Yin S, Gelin CF, et al. Identification of a novel small molecule HIF-1alpha translation inhibitor. Clin Cancer Res, 2009, 15(19): 6128-6136.
[2].  Li J, Jiang G, Chen Y, et al. Altered expression of hypoxia-Inducible factor-1α participates in the epileptogenesis in animal models. Synapse, 2014, 68(9): 402-409.