GC7 is an inhibitor of deoxyhypusine synthase (Ki = 9.7 nM), an enzyme that participates in the biosynthesis of the amino acid hypusine, which is formed post-translationally on eukaryotic initiation factor 5A (eIF5A).1 It inhibits the production of hypusine in CHO cells when used at a concentration of 1 ?M. GC7 (20 ?M) inhibits activation of eIF5A2 and enhances the cytotoxicity of doxorubicin in Huh7 and HepG2 cells.2 It reduces tumor growth in a Melan-a Tm5 murine melanoma model when administered at a dose of 0.9 mg/kg.3
1.Jakus, J., Wolff, E.C., Park, M.H., et al.Features of the spermidine-binding site of deoxyhypusine synthase as derived from inhibition studies. Effective inhibition by bis- and mono-guanylated diamines and polyaminesJ. Biol. Chem.268(18)13151-13159(1993) 2.Lou, B., Fan, J., Wang, K., et al.N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of doxorubicin by inhibiting activation of eukaryotic translation initiation factor 5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in hepatocellular carcinoma cellsExp. Cell Res.319(17)2708-2717(2013) 3.Jasiulionis, M.G., Luchessi, A.D., Moreira, A.G., et al.Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growthCell Biochem. Funct.25(1)109-114(2007)