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Identification
NameSpermine
Accession NumberDB00127  (DB02564, EXPT02947, NUTR00055)
Typesmall molecule
Groupsapproved, nutraceutical
Description

A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
4,9-Diaza-1,12-dodecanediamineNot AvailableNot Available
4,9-Diazadodecane-1,12-diamineNot AvailableNot Available
N,N'-Bis(3-aminopropyl)-1,4-butanediamineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Spermine dihydrate
Thumb Not applicable DBSALT000870
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number71-44-3
WeightAverage: 202.3402
Monoisotopic: 202.215746852
Chemical FormulaC10H26N4
InChI KeyInChIKey=PFNFFQXMRSDOHW-UHFFFAOYSA-N
InChI
InChI=1S/C10H26N4/c11-5-3-9-13-7-1-2-8-14-10-4-6-12/h13-14H,1-12H2
IUPAC Name
(3-aminopropyl)({4-[(3-aminopropyl)amino]butyl})amine
SMILES
NCCCNCCCCNCCCN
Mass Specshow(10.5 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsDialkylamines; Monoalkylamines
Substituentsprimary aliphatic amine; primary amine
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor nutritional supplementation, also for treating dietary shortage or imbalance
PharmacodynamicsSpermine is a polyamine. It is an organic molecule that is involved in cellular metabolism.
Mechanism of actionSpermine is derived from spermidine by spermine synthase. Spermine is a polyamine, a small organic cations that is absolutely required for eukaryotic cell growth. Spermine, is normally found in millimolar concentrations in the nucleus. Spermine functions directly as a free radical scavenger, and forms a variety of adducts that prevent oxidative damage to DNA. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. Hence, spermine is a major natural intracellular compound capable of protecting DNA from free radical attack. Spermine is also implicated in the regulation of gene expression, the stabilization of chromatin, and the prevention of endonuclease-mediated DNA fragmentation.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Spermidine and Spermine BiosynthesisMetabolicSMP00445
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9215
Blood Brain Barrier + 0.6345
Caco-2 permeable + 0.7072
P-glycoprotein substrate Non-substrate 0.5094
P-glycoprotein inhibitor I Non-inhibitor 0.9178
P-glycoprotein inhibitor II Non-inhibitor 0.6414
Renal organic cation transporter Non-inhibitor 0.6066
CYP450 2C9 substrate Non-substrate 0.8863
CYP450 2D6 substrate Non-substrate 0.5607
CYP450 3A4 substrate Non-substrate 0.8262
CYP450 1A2 substrate Inhibitor 0.877
CYP450 2C9 substrate Non-inhibitor 0.9072
CYP450 2D6 substrate Non-inhibitor 0.9502
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9703
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9386
Ames test Non AMES toxic 0.8957
Carcinogenicity Non-carcinogens 0.6436
Biodegradation Ready biodegradable 0.5525
Rat acute toxicity 2.4561 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7691
hERG inhibition (predictor II) Non-inhibitor 0.7739
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point29 °CPhysProp
boiling point150-150 °CNot Available
water solubility> 100 mg/mLNot Available
logP-0.7Not Available
Predicted Properties
PropertyValueSource
water solubility2.19e+00 g/lALOGPS
logP-0.66ALOGPS
logP-1.5ChemAxon
logS-2ALOGPS
pKa (strongest basic)11.1ChemAxon
physiological charge4ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count4ChemAxon
polar surface area76.1ChemAxon
rotatable bond count11ChemAxon
refractivity62.56ChemAxon
polarizability26.69ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Koji Nakanishi, Amira T. Eldefrawi, Mohyee E. Eldefrawi, Peter N. R. Usherwood, “Butyryl-tyrosinyl spermine, analogs thereof and methods of preparing and using same.” U.S. Patent US5770625, issued January, 1966.

US5770625
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC00750
PubChem Compound1103
PubChem Substance46507215
ChemSpider1072
ChEBI15746
ChEMBLCHEMBL23194
PharmGKBPA164781199
IUPHAR710
Guide to Pharmacology710
HETSPM
WikipediaSpermine
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(19.4 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Spermine synthase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Spermine synthase P52788 Details

References:

  1. Lopatin AN, Shantz LM, Mackintosh CA, Nichols CG, Pegg AE: Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000 Nov;32(11):2007-24. Pubmed
  2. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. Pubmed
  3. Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE: X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec;11(12):937-44. Pubmed
  4. Wang X, Ikeguchi Y, McCloskey DE, Nelson P, Pegg AE: Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004 Dec 3;279(49):51370-5. Epub 2004 Sep 30. Pubmed
  5. Schwartz CE, Wang X, Stevenson RE, Pegg AE: Spermine synthase deficiency resulting in x-linked intellectual disability (snyder-robinson syndrome). Methods Mol Biol. 2011;720:437-45. Pubmed
  6. Wang X, Pegg AE: Use of (gyro) gy and spermine synthase transgenic mice to study functions of spermine. Methods Mol Biol. 2011;720:159-70. Pubmed
  7. Theiss C, Bohley P, Voigt J: Regulation by polyamines of ornithine decarboxylase activity and cell division in the unicellular green alga Chlamydomonas reinhardtii. Plant Physiol. 2002 Apr;128(4):1470-9. Pubmed
  8. Krauss M, Langnaese K, Richter K, Brunk I, Wieske M, Ahnert-Hilger G, Veh RW, Laube G: Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment. J Neurochem. 2006 Apr;97(1):174-89. Epub 2006 Mar 3. Pubmed
  9. Kobayashi M, Takao K, Shiota Y, Sugita Y, Takahashi M, Nakae D, Samejima K: Inhibition of putrescine aminopropyltransferase influences rat liver regeneration. Biol Pharm Bull. 2006 May;29(5):863-7. Pubmed

2. Spermine oxidase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Spermine oxidase Q9NWM0 Details

References:

  1. Binda C, Angelini R, Federico R, Ascenzi P, Mattevi A: Structural bases for inhibitor binding and catalysis in polyamine oxidase. Biochemistry. 2001 Mar 6;40(9):2766-76. Pubmed
  2. Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW: Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem J. 2002 Nov 1;367(Pt 3):665-75. Pubmed
  3. Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW: Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion. Biochem J. 2003 Feb 15;370(Pt 1):19-28. Pubmed
  4. Wang Y, Murray-Stewart T, Devereux W, Hacker A, Frydman B, Woster PM, Casero RA Jr: Properties of purified recombinant human polyamine oxidase, PAOh1/SMO. Biochem Biophys Res Commun. 2003 May 16;304(4):605-11. Pubmed
  5. Bacchi CJ, Rattendi D, Faciane E, Yarlett N, Weiss LM, Frydman B, Woster P, Wei B, Marton LJ, Wittner M: Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues. Microbiology. 2004 May;150(Pt 5):1215-24. Pubmed

3. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details

References:

  1. Trubetskoy VS, Wolff JA, Budker VG: The role of a microscopic colloidally stabilized phase in solubilizing oligoamine-condensed DNA complexes. Biophys J. 2003 Feb;84(2 Pt 1):1124-30. Pubmed
  2. Cho SK, Kwon YJ: Polyamine/DNA polyplexes with acid-degradable polymeric shell as structurally and functionally virus-mimicking nonviral vectors. J Control Release. 2010 Dec 16. Pubmed
  3. Saminathan M, Thomas T, Shirahata A, Pillai CK, Thomas TJ: Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: potential applications to DNA packaging, gene therapy and polyamine therapeutics. Nucleic Acids Res. 2002 Sep 1;30(17):3722-31. Pubmed

4. Ornithine decarboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: product of

Components

Name UniProt ID Details
Ornithine decarboxylase P11926 Details

References:

  1. Nilsson J, Grahn B, Heby O: Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression. Biochem J. 2000 Mar 15;346 Pt 3:699-704. Pubmed
  2. Ray RM, Viar MJ, Yuan Q, Johnson LR: Polyamine depletion delays apoptosis of rat intestinal epithelial cells. Am J Physiol Cell Physiol. 2000 Mar;278(3):C480-9. Pubmed
  3. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. Pubmed
  4. Rohn G, Els T, Hell K, Ernestus RI: Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors. Neurochem Int. 2001 Aug;39(2):135-40. Pubmed
  5. Ernestus RI, Rohn G, Schroder R, Els T, Klekner A, Paschen W, Klug N: Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry. J Neurol Neurosurg Psychiatry. 2001 Jul;71(1):88-92. Pubmed
  6. Lee NK, Maclean HE: Polyamines, androgens and skeletal muscle hypertrophy. J Cell Physiol. 2010 Dec 7. Pubmed

1. Xanthine dehydrogenase/oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

References:

  1. Lovaas E, Carlin G: Spermine: an anti-oxidant and anti-inflammatory agent. Free Radic Biol Med. 1991;11(5):455-61. Pubmed

2. Diamine acetyltransferase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Diamine acetyltransferase 1 P21673 Details

References:

  1. Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer DL, Janne J, Porter CW: Effects of conditional overexpression of spermidine/spermine N1-acetyltransferase on polyamine pool dynamics, cell growth, and sensitivity to polyamine analogs. J Biol Chem. 2000 Dec 8;275(49):38319-28. Pubmed
  2. Hegardt C, Andersson G, Oredsson SM: Changes in polyamine metabolism during glucocorticoid-induced programmed cell death in mouse thymus. Cell Biol Int. 2000;24(12):871-80. Pubmed
  3. Marverti G, Bettuzzi S, Astancolle S, Pinna C, Monti MG, Moruzzi MS: Differential induction of spermidine/spermine N1-acetyltransferase activity in cisplatin-sensitive and -resistant ovarian cancer cells in response to N1,N12-bis(ethyl)spermine involves transcriptional and post-transcriptional regulation. Eur J Cancer. 2001 Jan;37(2):281-9. Pubmed
  4. Scorcioni F, Corti A, Davalli P, Astancolle S, Bettuzzi S: Manipulation of the expression of regulatory genes of polyamine metabolism results in specific alterations of the cell-cycle progression. Biochem J. 2001 Feb 15;354(Pt 1):217-23. Pubmed
  5. Min SH, Simmen RC, Alhonen L, Halmekyto M, Porter CW, Janne J, Simmen FA: Altered levels of growth-related and novel gene transcripts in reproductive and other tissues of female mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT). J Biol Chem. 2002 Feb 1;277(5):3647-57. Epub 2001 Nov 14. Pubmed
  6. Limsuwun K, Jones PG: Spermidine acetyltransferase is required to prevent spermidine toxicity at low temperatures in Escherichia coli. J Bacteriol. 2000 Oct;182(19):5373-80. Pubmed

3. Diamine acetyltransferase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Diamine acetyltransferase 2 Q96F10 Details

References:

  1. Chen Y, Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW: Genomic identification and biochemical characterization of a second spermidine/spermine N1-acetyltransferase. Biochem J. 2003 Aug 1;373(Pt 3):661-7. Pubmed
  2. Coleman CS, Stanley BA, Jones AD, Pegg AE: Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylates thialysine and is not involved in polyamine metabolism. Biochem J. 2004 Nov 15;384(Pt 1):139-48. Pubmed
  3. Vogel NL, Boeke M, Ashburner BP: Spermidine/Spermine N1-Acetyltransferase 2 (SSAT2) functions as a coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance NF-kappaB-dependent transcription. Biochim Biophys Acta. 2006 Oct;1759(10):470-7. Epub 2006 Aug 30. Pubmed
  4. Limsuwun K, Jones PG: Spermidine acetyltransferase is required to prevent spermidine toxicity at low temperatures in Escherichia coli. J Bacteriol. 2000 Oct;182(19):5373-80. Pubmed

1. Solute carrier family 22 member 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 4 Q9H015 Details

References:

  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08