Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1099210.32607/actanaturae.10992Research ArticlesЭкспериментальные статьиResearch ArticleIdentification of a novel substrate-derived spermine oxidase inhibitorDunstonT. T.
United States
tdunsto1@jhmi.edu6504195660G-2234-2015KhomutovM. A.
Russian Federation

PhD, Senior Researcher, MODFAS Laboratory

makhomutov@mail.ruGabelliS. B.
United States
tmurray2@jhmi.eduStewartT. M.
United States
jfoley13@jhmi.eduFoleyJ. R.
Russian Federation
kochet@eimb.ruKochetkovS. N.
Russian Federation
alexkhom@list.ruKhomutovA. R.
United States
rcasero@jhmi.eduCasero Jr.R. A.
United States
rcasero@jhmi.eduSidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine2Engelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesThe Johns Hopkins University School of MedicineSidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of MedicineEngelhardt Institute of Molecular Biology, Russian Academy of SciencesSidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine271020201231401440805202021072020Copyright ©; 2020, Dunston T.T., Khomutov M.A., Gabelli S.B., Stewart T.M., Foley J.R., Kochetkov S.N., Khomutov A.R., Casero Jr. R.A.Copyright ©; 2020, Dunston T., Khomutov M., Gabelli S., Stewart T., Foley J., Kochetkov S., Khomutov A., Casero Jr. R.2020Dunston T.T., Khomutov M.A., Gabelli S.B., Stewart T.M., Foley J.R., Kochetkov S.N., Khomutov A.R., Casero Jr. R.A.Dunston T., Khomutov M., Gabelli S., Stewart T., Foley J., Kochetkov S., Khomutov A., Casero Jr. R.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10992

Homeostasis of the biogenic polyamines spermine (Spm) and spermidine (Spd), present in μM-mM concentrations in all eukaryotic cells, is precisely regulated by coordinated activities of the enzymes of polyamine synthesis, degradation, and transport, in order to sustain normal cell growth and viability. Spermine oxidase (SMOX) is the key and most recently discovered enzyme of polyamine metabolism that plays an essential role in regulating polyamine homeostasis by catalyzing the back-conversion of Spm to Spd. The development of many types of epithelial cancer is associated with inflammation, and disease-related inflammatory stimuli induce SMOX. MDL72527 is widely used in vitro and in vivo as an irreversible inhibitor of SMOX, but it is also potent towards N1-acetylpolyamine oxidase. Although SMOX has high substrate specificity, Spm analogues have not been systematically studied as enzyme inhibitors. Here we demonstrate that 1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane (2,11-Met2-Spm) has, under standard assay conditions, an IC50 value of 169 μM towards SMOX and is an interesting instrument and lead compound for studying polyamine catabolism.

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