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A cell-permeable N, N'-diarylurea that acts as an inhibitor of the formation of the ternary complex of eukaryotic translation initiation factor 2 (eIF2), GTP and the initiator methionine tRNA (Met-tRNAi), a key regulatory step of translation initiation. It directly activates heme-regulated inhibitor kinase (HRI), which then phosphorylates eIF2α in cells at 10μM and in cell-free extracts dose-dependently, and thereby prevents respective ternary complex formation without elevating oxidative stress. The sensitivities of various cancer cell lines to the anti-proliferative effects of this compound are shown to correlate with the expression of HRI. Furthermore, this compound displays tumor growth inhibition in a mice xenograft model of MCF-7 human breast cancer cells at 175mg/kg, in vivo .
