生物活性

• 描述The response of mammalian cells to hypoxia is mediated by a family of transcription factors known as HIF (hypoxia-inducible factors). The subunits of HIF, HIF-1α can be degraded rapidly under normoxia. KC7F2 is a HIF-1α inhibitor, which can inhibit the HIF-1α biological activity with IC50 value of 20μM (measured by HIF-1–responsive promoter) under hypoxia (1% O₂). Accompanied with the inhibited activity of HIF-1α, treatment with KC7F2 40μM for 24h decreased the transcription of defined HIF-1α target genes, including carbonic anhydrase IX, MMP2, endothelin1 and enolase 1 in LN229 cells. KC7F2 has cytotoxicity in MCF7, LNZ308, A549, U251MG and LN229 with IC50 of approximately 15-25μM for 72h under normoxia, but is more severe under hypoxic conditions in other cell lines, such as D54MG. KC7F2 can also reduce the protein levels of HIF-1α in cancer cell lines of different tissue origin and genetic background, including U251MG, MCF7, PC3 and LNZ308 cells, on concentration of 40μM for 8 or 24 h under hypoxia, as well as in LN229 cells dose-dependently (20-80μM for 6h) ^[1].
• 作用机制KC7F2 inhibits HIF-1α protein synthesis with no effect on neither the mRNA transcription nor the protein degradation rate of HIF-1α. The accurate mechanism of its action is unknown, but may involve in inhibition of the phosphorylation of 4EBP1 and S6K.^[1]