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
Deferoxamin
Deferoxamina
Déferoxamine
Deferoxaminum
Deferrioxamine
Deferrioxamine b
Desferrioxamine
DFO
DFOA
DFOM
External IDs Ba 29837 / Ba 33112
Product Ingredients
IngredientUNIICASInChI KeyDetails
Deferoxamine HydrochlorideG9VYJ96FOJ 1950-39-6KCRQZLMAZHZDCL-UHFFFAOYSA-NDetails
Deferoxamine mesylateV9TKO7EO6K 138-14-7IDDIJAWJANBQLJ-UHFFFAOYSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Deferoxamine Mesylate for InjectionPowder, for solution500 mgIntramuscular; Intraperitoneal; Intravenous; SubcutaneousHospira, Inc.2000-04-12Not applicableCanada
Deferoxamine Mesylate for InjectionPowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
Deferoxamine Mesylate for InjectionPowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousHospira, Inc.2004-01-12Not applicableCanada
DesferalInjection, powder, lyophilized, for solution2 g/1Intramuscular; Intravenous; SubcutaneousNovartis1968-04-022017-07-31Us
DesferalInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; SubcutaneousNovartis1968-04-02Not applicableUs
Desferal 2gPowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousNovartis1992-12-312016-10-31Canada
Desferal 500mgPowder, for solution500 mgIntramuscular; Intraperitoneal; Intravenous; SubcutaneousNovartis1992-12-31Not applicableCanada
PMS-deferoxaminePowder, for solution500 mgIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPharmascience Inc2000-05-24Not applicableCanada
PMS-deferoxaminePowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPharmascience Inc2001-08-21Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DeferoxamineInjection, powder, lyophilized, for solution95 mg/mLIntramuscular; Intravenous; SubcutaneousAPP Pharmaceuticals, Inc.2009-12-15Not applicableUs
DeferoxamineInjection, powder, lyophilized, for solution95 mg/mLIntramuscular; Intravenous; SubcutaneousAPP Pharmaceuticals, Inc.2009-12-15Not applicableUs
Deferoxamine MesylateInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; SubcutaneousHospira, Inc.2004-03-17Not applicableUs
Deferoxamine MesylateInjection, powder, lyophilized, for solution2 g/1Intramuscular; Intravenous; SubcutaneousHospira, Inc.2004-03-17Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DesferinNovartis
Brand mixturesNot Available
Categories
UNIIJ06Y7MXW4D
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
Pharmacology
Indication

Used 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.

Structured Indications
Pharmacodynamics

Deferoxamine, 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 action

Deferoxamine 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
IronSmall moleculeyes
chelator
Humannot applicabledetails
AluminumSmall moleculeyes
chelator
Humannot applicabledetails
Related Articles
Absorption

Deferoxamine 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 binding

Less 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 elimination

Deferoxamine 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 life

Biphasic 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
Toxicity

Intravenous 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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
ProchlorperazineThe risk or severity of adverse effects can be increased when Deferoxamine is combined with Prochlorperazine.Approved, Vet Approved
Vitamin CThe risk or severity of adverse effects can be increased when Vitamin C is combined with Deferoxamine.Approved, Nutraceutical
Food InteractionsNot 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 References
  1. Link [Link]
External Links
ATC CodesV03AC01
AHFS Codes
  • 64:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (52.1 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionProblem of Aging / Stroke1
0TerminatedTreatmentSubarachnoid Hemorrhage1
1CompletedOtherIntracerebral Hemorrhage1
1CompletedTreatmentImmune Abnormalities1
1, 2CompletedTreatmentBeta-Thalassemia1
1, 2Not Yet RecruitingTreatmentIntracranial Aneurysms / Subarachnoid Hemorrhage1
1, 2RecruitingTreatmentIntracerebral Hemorrhage1
1, 2Unknown StatusTreatmentThalassemias1
2CompletedTreatmentAcute Ischemic Stroke (AIS)1
2CompletedTreatmentAcute Renal Failure / Hypotension1
2CompletedTreatmentAcute iron intoxication / Anemia (Iron-Loading) / Beta-Thalassemia / Hematologic Diseases / Hemochromatosis / Hemoglobinopathies / Thalassemias1
2CompletedTreatmentCardiac Iron Overload1
2CompletedTreatmentCardiac Iron Overload / Transfusion-dependent β-thalassemia Patients1
2CompletedTreatmentHemochromatosis1
2CompletedTreatmentAcute iron intoxication / Hemolytic Anemia / Sickle Cells Disease1
2CompletedTreatmentAcute iron intoxication / Myelodysplastic Syndrome1
2CompletedTreatmentSickle Cell Anemia1
2CompletedTreatmentTransfusional Hemosiderosis / Transfusional Iron Overload1
2Not Yet RecruitingTreatmentDiabetic Foot Ulcers (DFU)1
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
2RecruitingTreatmentIntracerebral Hemorrhage1
2SuspendedTreatmentIntracerebral Hemorrhage1
2TerminatedTreatmentBeta-Thalassemia / Cardiovascular Disease (CVD) / Heart Diseases1
2, 3Unknown StatusTreatmentBeta-Thalassemia Major / Iron Hemosiderosis / Sickle Cells Disease1
3CompletedTreatmentBeta-Thalassemia1
3CompletedTreatmentHemochromatosis1
4CompletedTreatmentBeta-Thalassemia / Thalassemia Major (TM)1
4CompletedTreatmentHemosiderosis / Thalassemia Major (TM)1
4CompletedTreatmentSickle Cells Disease / Thalassemia Major (TM) / Transfusion-dependent Hemachromatosis1
4CompletedTreatmentAcute iron intoxication / Thalassemias1
4CompletedTreatmentAcute iron intoxication / Prophylaxis of cardiomyopathy1
4RecruitingTreatmentAcute iron intoxication / Other Anemias / Sickle Cells Disease1
Not AvailableCompletedNot AvailableAcute iron intoxication / Anemia, Cooley's / Beta-Thalassemia / Hematologic Diseases / Osteoporosis / Pulmonary Hypertension (PH) / Thalassemias1
Not AvailableCompletedTreatmentAcute iron intoxication / Thalassemias / Transfusion Related Complications1
Not AvailableTerminatedPreventionAcute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukaemias (AML) / Myelodysplastic Syndrome1
Not AvailableUnknown StatusTreatmentBeta-Thalassemia / Iron Chelation Therapy / Serum Ferritin1
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; Subcutaneous95 mg/mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Subcutaneous2 g/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Subcutaneous500 mg/1
Powder, for solutionIntramuscular; Intraperitoneal; Intravenous; Subcutaneous500 mg
Powder, for solutionIntramuscular; Intraperitoneal; Intravenous; Subcutaneous2 g
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 point (°C)140 °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
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 inhibitorNon-inhibitor0.8442
CYP450 2D6 inhibitorNon-inhibitor0.9103
CYP450 2C19 inhibitorNon-inhibitor0.8236
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udl-0892110000-487a5822b41da03f0948View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0007-9621400000-9b6a525f53e7f320f714View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ikc-1771190000-39b4db7f6f66f4b9474eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0111190000-7dabe399b61bdc270ec0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as acetohydroxamic acids. These are organic compounds that contain a hydroxamic acid group carrying a methyl group attached to its carbon center.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentAcetohydroxamic acids
Alternative Parents
Substituents
  • Acetamide
  • Acetohydroxamic acid
  • Amino acid or derivatives
  • Carboximidic acid
  • Carboximidic acid derivative
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Carbonyl group
  • Organic nitrogen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors

Targets

1. Iron
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
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:9549639 ]
  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:16339658 ]
  3. Cappellini MD, Musallam KM, Taher AT: Overview of iron chelation therapy with desferrioxamine and deferiprone. Hemoglobin. 2009;33 Suppl 1:S58-69. doi: 10.3109/03630260903346924. [PubMed:20001633 ]
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
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:7482575 ]
  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:8301696 ]
  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:8122301 ]
  4. Domingo JL: The use of chelating agents in the treatment of aluminum overload. J Toxicol Clin Toxicol. 1989;27(6):355-67. [PubMed:2697761 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xanthine oxidase activity
Specific Function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular Weight:
146422.99 Da
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:2252579 ]
Drug created on June 13, 2005 07:24 / Updated on May 19, 2017 16:38