Identification of a Novel SubstrateDerived Spermine Oxidase Inhibitor

T. T. Dunston; M. A. Khomutov; S. B. Gabelli; T. M. Stewart; J. R. Foley; S. N. Kochetkov; A. R. Khomutov; R. A. Casero

doi:10.32607/actanaturae.10992

Identification of a Novel SubstrateDerived Spermine Oxidase Inhibitor

T. T. Dunston, M. A. Khomutov, S. B. Gabelli, T. M. Stewart, J. R. Foley, S. N. Kochetkov, A. R. Khomutov, R. A. Casero

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	140-144
Number of pages	5
Journal	Acta Naturae
Volume	12
Issue number	3
DOIs	https://doi.org/10.32607/actanaturae.10992
State	Published - 2020

Keywords

2,11-Met2-Spm
MDL72527
Spermine oxidase
inhibitors
spermine analogues

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Medicine
Molecular Biology

Access to Document

10.32607/actanaturae.10992

Cite this

@article{333173674c79488eb38e685e788735c3,

title = "Identification of a Novel SubstrateDerived Spermine Oxidase Inhibitor",

abstract = "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.",

keywords = "2,11-Met2-Spm, MDL72527, Spermine oxidase, inhibitors, spermine analogues",

author = "Dunston, {T. T.} and Khomutov, {M. A.} and Gabelli, {S. B.} and Stewart, {T. M.} and Foley, {J. R.} and Kochetkov, {S. N.} and Khomutov, {A. R.} and Casero, {R. A.}",

note = "Funding Information: Synthesis of the inhibitor was supported by the Russian Science Foundation grant 17-74-20049 (AMK and ARK). Inhibition studies were supported by the National Institutes of Health grants NCI R01CA204234 and RO1CA235863 (RAC). This work was supported by a research grant from the University of Pennsylvania Orphan Disease Center in partnership with the Snyder-Robinson Foundation MDBR-20-135-SRS (RAC, TMS). We would like to thank Dr. Michelle S. Miller and Puchong Thirawatananond for their help in designing the purification protocol of SMOX. Publisher Copyright: {\textcopyright} 2020. All rights reserved.",

year = "2020",

doi = "10.32607/actanaturae.10992",

language = "English (US)",

volume = "12",

pages = "140--144",

journal = "Acta Naturae",

issn = "2075-8251",

publisher = "Park Media Ltd.",

number = "3",

}

TY - JOUR

T1 - Identification of a Novel SubstrateDerived Spermine Oxidase Inhibitor

AU - Dunston, T. T.

AU - Khomutov, M. A.

AU - Gabelli, S. B.

AU - Stewart, T. M.

AU - Foley, J. R.

AU - Kochetkov, S. N.

AU - Khomutov, A. R.

AU - Casero, R. A.

N1 - Funding Information: Synthesis of the inhibitor was supported by the Russian Science Foundation grant 17-74-20049 (AMK and ARK). Inhibition studies were supported by the National Institutes of Health grants NCI R01CA204234 and RO1CA235863 (RAC). This work was supported by a research grant from the University of Pennsylvania Orphan Disease Center in partnership with the Snyder-Robinson Foundation MDBR-20-135-SRS (RAC, TMS). We would like to thank Dr. Michelle S. Miller and Puchong Thirawatananond for their help in designing the purification protocol of SMOX. Publisher Copyright: © 2020. All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - 2,11-Met2-Spm

KW - MDL72527

KW - Spermine oxidase

KW - inhibitors

KW - spermine analogues

UR - http://www.scopus.com/inward/record.url?scp=85100180052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85100180052&partnerID=8YFLogxK

U2 - 10.32607/actanaturae.10992

DO - 10.32607/actanaturae.10992

M3 - Article

C2 - 33173604

AN - SCOPUS:85100180052

SN - 2075-8251

VL - 12

SP - 140

EP - 144

JO - Acta Naturae

JF - Acta Naturae

IS - 3

ER -

Identification of a Novel SubstrateDerived Spermine Oxidase Inhibitor

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this