Echinomycin

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that controls genes involved in glycolysis, angiogenesis, migration, and invasion. Echinomycin is a cell-permeable inhibitor of HIF-1-mediated gene transcription.{20741,20742} It acts by intercalating into DNA in a sequence-specific manner, blocking the binding of either HIF-1? or HIF-1? to the hypoxia-responsive element.{20741,20742,20743} Echinomycin reversibly inhibits hypoxia-induced HIF-1 transcription activity in U215 cells with an EC50 value of 1.2 nM.{20741} It inhibits hypoxia-induced expression of vascular endothelial growth factor, blocking angiogenesis and altering excitatory synaptic transmission in hippocampal neurons.{20742,20740} Echinomycin also impairs expression of survivin, enhancing the sensitivity of multiple myeloma cells to melphalan.{20739}