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Identification
NameDeferoxamine
Accession NumberDB00746  (APRD00904)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
DeferoxaminGermanINN
DeferoxaminaSpanishINN
DéferoxamineFrenchINN
DeferoxaminumLatinINN
DeferrioxamineNot AvailableNot Available
Deferrioxamine bNot AvailableNot Available
DesferrioxamineNot AvailableBAN
DFONot AvailableNot Available
DFOANot AvailableIS
DFOMNot AvailableIS
Salts
Name/CAS Structure Properties
Deferoxamine Hydrochloride
Thumb Not applicable DBSALT000965
Deferoxamine mesylate
Thumb Not applicable DBSALT000964
Brand names
NameCompany
DesferalNovartis
DesféralNovartis
DesferinNovartis
Brand mixturesNot Available
Categories
CAS number70-51-9
WeightAverage: 560.684
Monoisotopic: 560.353362542
Chemical FormulaC25H48N6O8
InChI KeyUBQYURCVBFRUQT-UHFFFAOYSA-N
InChI
InChI=1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)
IUPAC Name
N-(5-aminopentyl)-N-hydroxy-N'-[5-(N-hydroxy-3-{[5-(N-hydroxyacetamido)pentyl]carbamoyl}propanamido)pentyl]butanediamide
SMILES
CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassCarboxylic Acid Derivatives
Direct parentSecondary Carboxylic Acid Amides
Alternative parentsPolyamines; Enolates; Carboxylic Acids; Monoalkylamines
Substituentscarboxylic acid; enolate; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the secondary carboxylic acid amides. These are compounds containing a secondary carboxylic acid amide functional group, with the general structure RC(=O)N(R')H (R,R'=alkyl, aryl).
Pharmacology
IndicationUsed to treat acute iron or aluminum toxicity (an excess of aluminum in the body) in certain patients. Also used in certain patients with anemia who must receive many blood transfusions.
PharmacodynamicsDeferoxamine, otherwise known as desferrioxamine or desferal, is a chelating agent used to remove excess iron or aluminum from the body. It acts by binding free iron or aluminum in the bloodstream and enhancing its elimination in the urine. By removing excess iron or aluminum, the agent reduces the damage done to various organs and tissues, such as the liver.
Mechanism of actionDeferoxamine works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming ferrioxamine, a stable complex which is eliminated via the kidneys. 100 mg of deferoxamine is capable of binding approximately 8.5 mg of trivalent (ferric) iron. Deferoxamine works in treating aluminum toxicity by binding to tissue-bound aluminum to form aluminoxamine, a stable, water-soluble complex. The formation of aluminoxamine increases blood concentrations of aluminum, resulting in an increased concentration gradient between the blood and dialysate, boosting the removal of aluminum during dialysis. 100 mg of deferoxamine is capable of binding approximately 4.1 mg of aluminum.
AbsorptionDeferoxamine is rapidly absorbed after intramuscular or subcutaneous administration, but only poorly absorbed from the gastrointestinal tract in the presence of intact mucosa.
Volume of distributionNot Available
Protein bindingLess than 10% bound to serum proteins in vitro.
Metabolism

Deferoxamine is mainly metabolised in the plasma and hepatic metabolism is minimal. A number of metabolites have been isolated but not characterised. Some metabolites of deferoxamine, most notably the product of oxidative deamination, also chelate iron, and thus the antidotal effect of the drug appears unaffected by hepatic metabolism.

Route of eliminationDeferoxamine mesylate is metabolized principally by plasma enzymes, but the pathways have not yet been defined. Some is also excreted in the feces via the bile.
Half lifeBiphasic elimination pattern in healthy volunteers with a first rapid phase half life of 1 hour and a second slow phase half-life of 6 hours.
ClearanceNot Available
ToxicityIntravenous LD50 in mouse, rat, and rabbit is 340 mg/kg, 520 mg/kg, and 600 mg/kg, respectively. Subcutaneous LD50 in mouse and rat is 1600 mg/kg and >1000 mg/kg, respectively. Oral LD50 in mouse and rat is >3000 mg/kg and >1000 mg/kg, respectively. Nephrotoxicity, ototoxicity and retinal toxicity have been reported following long-term administration for chronic iron overload.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.5
Blood Brain Barrier + 0.9242
Caco-2 permeable - 0.8957
P-glycoprotein substrate Substrate 0.5
P-glycoprotein inhibitor I Non-inhibitor 0.8856
P-glycoprotein inhibitor II Non-inhibitor 0.9649
Renal organic cation transporter Non-inhibitor 0.9141
CYP450 2C9 substrate Non-substrate 0.8027
CYP450 2D6 substrate Non-substrate 0.7876
CYP450 3A4 substrate Non-substrate 0.6312
CYP450 1A2 substrate Non-inhibitor 0.8767
CYP450 2C9 substrate Non-inhibitor 0.8442
CYP450 2D6 substrate Non-inhibitor 0.9103
CYP450 2C19 substrate Non-inhibitor 0.8236
CYP450 3A4 substrate Non-inhibitor 0.7574
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9786
Ames test AMES toxic 0.5388
Carcinogenicity Non-carcinogens 0.6595
Biodegradation Not ready biodegradable 0.8749
Rat acute toxicity 2.0628 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9839
hERG inhibition (predictor II) Non-inhibitor 0.7688
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Watson laboratories inc
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular
Powder, for solutionIntraperitoneal
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Desferal 2 gram vial113.94USDvial
Desferal 2 g/vial60.52USDvial
Deferoxamine 2 gram vial46.25USDvial
Desferrioxamine Mesilate 2 g/vial33.89USDvial
Pms-Deferoxamine 2 g/vial33.89USDvial
Desferal 500 mg Solution Vial23.92USDvial
Desferal 500 mg/vial15.07USDvial
Desferrioxamine Mesilate 500 mg/vial8.44USDvial
Pms-Deferoxamine 500 mg/vial8.44USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point140 °CPhysProp
water solubility1.2E+004 mg/L (at 20 °C)MERCK INDEX (1996)
logP-2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.099ALOGPS
logP0.93ALOGPS
logP-3.4ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.92ChemAxon
pKa (Strongest Basic)10.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area205.84 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity144.95 m3·mol-1ChemAxon
Polarizability62.41 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Zoltan Konyari, Vilmos Keri, Antal Kovacs, Sandor Horkay, Laszlo Eszenyi, Janos Erdelyi, Ilona Himesi, Gyorgy Toth, Janos Balint, SzilaJudit, Ferenc Vinczi, Csaba Szabo, Nelli Sas, “Process for the preparation of high-purity deferoxamine salts.” U.S. Patent US5374771, issued July, 1965.

US5374771
General Reference
  1. Link
External Links
ResourceLink
KEGG DrugD03670
KEGG CompoundC06940
PubChem Compound2973
PubChem Substance46506395
ChemSpider2867
ChEBI4356
ChEMBLCHEMBL556
PharmGKBPA164746490
Drug Product Database2243450
Drugs.comhttp://www.drugs.com/cdi/deferoxamine.html
WikipediaDeferoxamine
ATC CodesV03AC01
AHFS Codes
  • 64:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(52.1 KB)
Interactions
Drug Interactions
Drug
Vitamin CVitamin C may increase the adverse effects of deferoxamine. Transient deterioration of left ventricular function has been observed during concomitant therapy. Use caution during concomitant therapy.
Food InteractionsNot Available

Targets

1. Iron

Kind: small molecule

Organism: Human

Pharmacological action: yes

Actions: chelator

Components

Name UniProt ID Details

References:

  1. Elihu N, Anandasbapathy S, Frishman WH: Chelation therapy in cardiovascular disease: ethylenediaminetetraacetic acid, deferoxamine, and dexrazoxane. J Clin Pharmacol. 1998 Feb;38(2):101-5. Pubmed
  2. Hershko C, Link G, Konijn AM, Cabantchik ZI: Objectives and mechanism of iron chelation therapy. Ann N Y Acad Sci. 2005;1054:124-35. Pubmed
  3. Cappellini MD, Musallam KM, Taher AT: Overview of iron chelation therapy with desferrioxamine and deferiprone. Hemoglobin. 2009;33 Suppl 1:S58-69. Pubmed

2. Aluminum

Kind: small molecule

Organism: Human

Pharmacological action: yes

Actions: chelator

Components

Name UniProt ID Details

References:

  1. Kontoghiorghes GJ: Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs. Toxicol Lett. 1995 Oct;80(1-3):1-18. Pubmed
  2. Yokel RA: Aluminum chelation: chemistry, clinical, and experimental studies and the search for alternatives to desferrioxamine. J Toxicol Environ Health. 1994 Feb;41(2):131-74. Pubmed
  3. Day JP, Ackrill P: The chemistry of desferrioxamine chelation for aluminum overload in renal dialysis patients. Ther Drug Monit. 1993 Dec;15(6):598-601. Pubmed
  4. Domingo JL: The use of chelating agents in the treatment of aluminum overload. J Toxicol Clin Toxicol. 1989;27(6):355-67. Pubmed

Enzymes

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. Rinaldo JE, Gorry M: Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase. Am J Respir Cell Mol Biol. 1990 Dec;3(6):525-33. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 06, 2014 11:42