You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Desferalinjection, powder, lyophilized, for solution2000 mgintramuscular; intravenous; subcutaneousNovartis Pharmaceuticals Corporation1968-04-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Desferalinjection, powder, lyophilized, for solution500 mgintramuscular; intravenous; subcutaneousNovartis Pharmaceuticals Corporation1968-04-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Deferoxamine Mesylateinjection, powder, lyophilized, for solution500 mgintramuscular; intravenous; subcutaneousHospira, Inc.2004-03-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Deferoxamine Mesylateinjection, powder, lyophilized, for solution500 mgintramuscular; intravenous; subcutaneousHospira, Inc.2004-03-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Deferoxamine Mesylateinjection, powder, lyophilized, for solution2 gintramuscular; intravenous; subcutaneousHospira, Inc.2004-03-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Deferoxamine Mesylateinjection, powder, lyophilized, for solution2 gintramuscular; intravenous; subcutaneousHospira, Inc.2004-03-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Deferoxamineinjection, powder, lyophilized, for solution95 mg/mLintramuscular; intravenous; subcutaneousAPP Pharmaceuticals, LLC2009-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Deferoxamineinjection, powder, lyophilized, for solution95 mg/mLintramuscular; intravenous; subcutaneousAPP Pharmaceuticals, LLC2009-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
DesferinNovartis
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Deferoxamine Hydrochloride
ThumbNot applicableDBSALT000965
Deferoxamine mesylate
ThumbNot applicableDBSALT000964
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl amines. These are compounds containing a fatty acid moiety linked to an amine group through an ester linkage.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty amides
Direct ParentN-acyl amines
Alternative Parents
Substituents
  • N-acyl-amine
  • Acetohydroxamic acid
  • Acetamide
  • Secondary carboxylic acid amide
  • Hydroxamic acid
  • Carboxamide group
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
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
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier+0.9242
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.8856
P-glycoprotein inhibitor IINon-inhibitor0.9649
Renal organic cation transporterNon-inhibitor0.9141
CYP450 2C9 substrateNon-substrate0.8027
CYP450 2D6 substrateNon-substrate0.7876
CYP450 3A4 substrateNon-substrate0.6312
CYP450 1A2 substrateNon-inhibitor0.8767
CYP450 2C9 substrateNon-inhibitor0.8442
CYP450 2D6 substrateNon-inhibitor0.9103
CYP450 2C19 substrateNon-inhibitor0.8236
CYP450 3A4 substrateNon-inhibitor0.7574
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9786
Ames testAMES toxic0.5388
CarcinogenicityNon-carcinogens0.6595
BiodegradationNot ready biodegradable0.8749
Rat acute toxicity2.0628 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9839
hERG inhibition (predictor II)Non-inhibitor0.7688
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Watson laboratories inc
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintramuscular; intravenous; subcutaneous2 g
Injection, powder, lyophilized, for solutionintramuscular; intravenous; subcutaneous2000 mg
Injection, powder, lyophilized, for solutionintramuscular; intravenous; subcutaneous500 mg
Injection, powder, lyophilized, for solutionintramuscular; intravenous; subcutaneous95 mg/mL
Prices
Unit descriptionCostUnit
Desferal 2 gram vial113.94USD vial
Desferal 2 g/vial60.52USD vial
Deferoxamine 2 gram vial46.25USD vial
Desferrioxamine Mesilate 2 g/vial33.89USD vial
Pms-Deferoxamine 2 g/vial33.89USD vial
Desferal 500 mg Solution Vial23.92USD vial
Desferal 500 mg/vial15.07USD vial
Desferrioxamine Mesilate 500 mg/vial8.44USD vial
Pms-Deferoxamine 500 mg/vial8.44USD vial
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 Solubility0.099 mg/mLALOGPS
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesV03AC01
AHFS Codes
  • 64:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (52.1 KB)
Interactions
Drug Interactions
Drug
ProchlorperazineMay enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported.
Vitamin CMay enhance the adverse/toxic effect of Deferoxamine. Left ventricular dysfunction is of particular concern.
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

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on January 06, 2014 11:42