A cell-permeable inhibitor that targets the spermidine-binding site of Deoxyhypusine Synthase (Ki = 9.7 nM), an enzyme which is responsible for the first step hypunisation of eukaryotic initiation factor 5A (eIF5A). In vivo, it demonstrates almost complete cessation of hypusine formation in CHO cells at ≥ 1 μM. Several studies indicate this compound as a useful tool for the down-regulation of eIF5A, a protein essential for cell proliferation. For example, it exhibits an anti-proliferative effect on both BCR-ABL -positive and -negative leukemia cell lines (K562 and HL-60) dose-dependently, at concentrations between 5 μM and 40 μM. In addition, it is shown to significantly impair the growth and invasion of primary HCC cells (HepG2 and Hep3B) in the 10-20 μM range, and against non-tumorigenic CL-48 cells at concentrations as high as 40 μM, with no apparent cytotoxicity. At 25 μM, GC7 treatment is shown to reverse eIF5a-mediated Skeletal Muscle Stem Cell Differentiation.
