产品描述:
The hypoxia-inducible factor (HIF) transcription factors are members of the basic-helix-loop-helix (bHLH) family of transcription factors and play important roles in maintaining cellular oxygen homeostasis.{11044,12428} HIF-1α has emerged as an important drug target in breast and prostate cancer, cardiovascular disease, and ischemia.{10724,11835} ML-228 is an activator of the HIF signaling pathway, as demonstrated by HIF response element (HRE) reporter assay (EC50 = 1.2 µM), HIF-1α nuclear translocation assay (EC50 = 1.3 µM), and increased VEGF expression (EC50 = 1.6 µM).{23099} Its activity in the HRE assay is blocked by excess iron, suggesting that ML-228 can chelate iron.{23099} Molecular modeling indicates that ML-228 does not modulate HIF signaling by binding to prolyl hydroxyases.{23099} ML-228 also significantly inhibits ligand binding to several channels, receptors, and transporters, including ERG potassium channel, 5-HT2B and A3 adenosine receptors, and dopamine transporter.{23099}