Literature Review

DHPS



Inhibitors

Inhibitors of DHPS include: GC7, Guanylhydrazone CNI-1493, and AXD455.

  • N(1)-guanyl-1,7,-diamineoheptane, an inhibitor of deoxyhypusine synthase, suppresses differentiation and induces apoptosis via mitochondrial and AMPK pathways in immortalized and malignant human oral keratinocytes. (PMID: 19656269,(ncbi.nlm.nih.gov)) Lee S.K. … Kim E.C. J. Oral Pathol. Med. 2009 22 64
    • GC7 was determined to be a growth inhibitor on human oral keratinocytes and primary oral cancer cells. GC7 blocks immortalized and malignant keratinocyte cell proliferation and differentiation by inducing apoptosis through the mitochondrial and AMPK pathways.
  • Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy. (PMID: 15630446,(ncbi.nlm.nih.gov)) Hauber I. … Hauber J. J. Clin. Invest. 2005 22 64
    • Guanylhydrazone CNI-1493 is an efficient inhibitor of DHPS. Inhibition of DHPS by CNI-1493 or RNA interference efficiently suppressed the retroviral replication cycle in cell culture and primary cells.
  • Screening assay for the identification of deoxyhypusine synthase inhibitors. (PMID: 15296643,(ncbi.nlm.nih.gov)) Sommer M.N. … Mett H. J Biomol Screen 2004 22 64
    • The authors developed a 96-well format DHS assay applicable for the screening of DHS inhibitors. Using this assay, they demonstrate DHS inhibition by AXD455.
  • Effect of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis. (PMID: 12236588,(ncbi.nlm.nih.gov)) Lee Y. … Joe Y.A. Mol. Cell. Biochem. 2002 22 64
    • This study examined the effects of GC7, a potent inhibitor of DHPS, on endothelial cell proliferation, differentiation, and apoptosis. The results suggest that eIF-5A may be involved in expression of proteins essential for cellular proliferation and apoptosis of endothelial cells.
  • Branched-chain and unsaturated 1,7-diaminoheptane derivatives as deoxyhypusine synthase inhibitors. (PMID: 9568280,(ncbi.nlm.nih.gov)) Lee Y.B. … Folk J.E. Bioorg. Med. Chem. 1998 22 64
    • Two series of 1,7-diaminoheptane derivatives were prepared and tested as inhibitors of human deoxyhypusine synthase.This research helps show the conformation of the substrate spermidine during its productive interaction at the active site of deoxyhypusine synthase.
  • Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. (PMID: 9244184,(ncbi.nlm.nih.gov)) Shi X.P. … Waxman L. Biochim. Biophys. Acta 1996 22 64
    • GC7 acts as a general antiproliferative agent related to its interference with the progression of cell cycle. GC7 does not appear to preferentially target tumorigenic cell types.
  • Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins. (PMID: 7673224,(ncbi.nlm.nih.gov)) Joe Y.A. … Park M.H. J. Biol. Chem. 1995 2 3 4 22 64
    • Human recombinant proteins with a truncation of 48 or 97 NH2-terminal amino acids; a truncation of 39 COOH-terminal amino acids; or an internal deletion (Asp262-Ser317) were inactive.
  • The role of hypusine depletion in cytostasis induced by S-adenosyl-L-methionine decarboxylase inhibition: new evidence provided by 1-methylspermidine and 1,12-dimethylspermine.(PMID: 7980394,(ncbi.nlm.nih.gov)) Byers T.L. … Pegg A.E. Biochem. J. 1994 22 64
    • AbeAdo-induced cytostasis was only reversed by polyamines and polyamine analogues that result in the formation of hypusine or an analogue in eIF-5A. This suggests that AbeAdo-induced cytostasis is due to the depletion of the hypusine-containing form of eIF-5A, which is secondary to the depletion of spermidine by inhibition of S-adenosyl-L-methionine decarboxylase.
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