IC50: 1.2 M for hypoxia-induced HIF-1 transcriptional activity

YC-1 is a novel anticancer drug initially developed as an inhibitor of HIF-1α. Hypoxia-inducible factor-1α (HIF-1α) is a basic helix-loop-helix transcription factor regulating expression of VEGF and other genes which modulate survival, growth and metastasis of tumor cells under conditions of hypoxia.

In vitro: YC-1 could inhibit platelet aggregation and vascular contraction via activating soluble guanylyl cyclase and was originally developed as a potential therapeutic agent for circulation disorders. YC-1 completely inhibited HIF-1α expression at the post-transcriptional level and consequently blocked the transcription factor activity of HIF-1 in hepatoma cells under hypoxic conditions, indicating that such effects of YC-1 were likely to be associated with the oxygen-sensing pathway but not with the soluble guanylyl cyclase activation [1].

In vivo: Compared with tumors from vehicle-treated mice, tumors from YC-1-treated group were found to be statistically smaller and less vascularized. In addition, tumors from YC-1-treated group expressed lower levels of HIF-1α as well as HIF-1-inducible genes, regardless of tumor type [1].

Clinical trial: N/A

Reference:
[1] Yeo EJ,Chun YS,Cho YS,Kim J,Lee JC,Kim MS,Park JW.  YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst.2003 Apr 2;95(7):516-25.