Identification

Name
Deferoxamine
Accession Number
DB00746  (APRD00904)
Type
Small Molecule
Groups
Approved, 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 / NSC-527604
Product Ingredients
IngredientUNIICASInChI Key
Deferoxamine HydrochlorideG9VYJ96FOJ1950-39-6KCRQZLMAZHZDCL-UHFFFAOYSA-N
Deferoxamine mesylateV9TKO7EO6K138-14-7IDDIJAWJANBQLJ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Deferoxamine Mesylate for InjectionPowder, for solution500 mgIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPfizer2000-04-12Not applicableCanada
Deferoxamine Mesylate for InjectionPowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPfizer2004-01-12Not applicableCanada
Deferoxamine Mesylate for InjectionPowder, for solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
DesferalInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; SubcutaneousNovartis1968-04-02Not applicableUs
DesferalInjection, powder, lyophilized, for solution2 g/1Intramuscular; Intravenous; SubcutaneousNovartis1968-04-022017-07-31Us
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 solution2 gIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPharmascience Inc2001-08-21Not applicableCanada
PMS-deferoxaminePowder, for solution500 mgIntramuscular; Intraperitoneal; Intravenous; SubcutaneousPharmascience Inc2000-05-24Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DeferoxamineInjection, powder, lyophilized, for solution95 mg/mLIntramuscular; Intravenous; SubcutaneousFresenius Kabi2009-12-15Not applicableUs
DeferoxamineInjection, powder, lyophilized, for solution95 mg/mLIntramuscular; Intravenous; SubcutaneousFresenius Kabi2009-12-15Not applicableUs
Deferoxamine MesylateInjection, powder, lyophilized, for solution2 g/1Intramuscular; Intravenous; SubcutaneousHospira, Inc.2004-03-17Not applicableUs
Deferoxamine mesylateInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; SubcutaneousGland Pharma Limited2017-10-09Not applicableUs
Deferoxamine MesylateInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; SubcutaneousHospira, Inc.2004-03-17Not applicableUs
Deferoxamine mesylateInjection, powder, lyophilized, for solution2 g/1Intramuscular; IntravenousGland Pharma Limited2017-10-09Not applicableUs
International/Other Brands
Desferin (Novartis)
Categories
UNII
J06Y7MXW4D
CAS number
70-51-9
Weight
Average: 560.684
Monoisotopic: 560.353362542
Chemical Formula
C25H48N6O8
InChI Key
UBQYURCVBFRUQT-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.

TargetActionsOrganism
AIron
chelator
Human
AAluminum
chelator
Human
UAmyloid beta A4 proteinNot AvailableHuman
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 distribution
Not 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.

Clearance
Not 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
Pathways
Not 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 Interactions
Not 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
Human Metabolome Database
HMDB14884
KEGG Drug
D03670
KEGG Compound
C06940
PubChem Compound
2973
PubChem Substance
46506395
ChemSpider
2867
BindingDB
47715
ChEBI
4356
ChEMBL
CHEMBL556
PharmGKB
PA164746490
Drugs.com
Drugs.com Drug Page
Wikipedia
Deferoxamine
ATC Codes
V03AC01 — Deferoxamine
AHFS Codes
  • 64:00.00 — Heavy Metal Antagonists
MSDS
Download (52.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionProblem of Aging / Strokes1
0TerminatedTreatmentSubarachnoid Hemorrhage1
1CompletedOtherIntracerebral Hemorrhage1
1CompletedTreatmentImmune Abnormalities1
1, 2CompletedTreatmentBeta-Thalassemia1
1, 2Not Yet RecruitingTreatmentIntracranial Aneurysms / Subarachnoid Hemorrhage1
1, 2RecruitingTreatmentIntracerebral Hemorrhage1
1, 2Unknown StatusTreatmentThalassaemic disorders1
2CompletedTreatmentAcute Ischemic Stroke (AIS)1
2CompletedTreatmentAcute Renal Failure (ARF) / Arterial Hypotension1
2CompletedTreatmentAcute iron intoxication / Anemia (Iron-Loading) / Beta-Thalassemia / Haemoglobinopathies congenital / Hematologic Diseases / Hemochromatosis / Thalassaemic disorders1
2CompletedTreatmentCardiac Iron Overload1
2CompletedTreatmentCardiac Iron Overload / Transfusion-dependent β-thalassemia Patients1
2CompletedTreatmentHemochromatosis1
2CompletedTreatmentAcute iron intoxication / Hemolytic Anemia / Sickle Cell Disorders1
2CompletedTreatmentAcute iron intoxication / Myelodysplastic Syndrome1
2CompletedTreatmentSickle Cell Disorders1
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 Cell Disorders1
3CompletedTreatmentBeta-Thalassemia1
3CompletedTreatmentHemochromatosis1
4CompletedTreatmentBeta-Thalassemia / Thalassemia Major (TM)1
4CompletedTreatmentHemosiderosis / Thalassemia Major (TM)1
4CompletedTreatmentSickle Cell Disorders / Thalassemia Major (TM) / Transfusion-dependent Hemachromatosis1
4CompletedTreatmentAcute iron intoxication / Thalassaemic disorders1
4CompletedTreatmentAcute iron intoxication / Prophylaxis of cardiomyopathy1
4RecruitingTreatmentAcute iron intoxication / Other Anemias / Sickle Cell Disorders1
Not AvailableCompletedNot AvailableAcute iron intoxication / Beta-Thalassemia / Bone destruction / Hematologic Diseases / Pulmonary Hypertension (PH) / Thalassaemic disorders / Thalassemia Major (TM)1
Not AvailableCompletedTreatmentAcute iron intoxication / Thalassaemic disorders / Transfusion Related Complications1
Not AvailableTerminatedPreventionAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (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; Intravenous2 g/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Subcutaneous500 mg/1
Powder, for solutionIntramuscular; Intraperitoneal; Intravenous; Subcutaneous2 g
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Subcutaneous2 g/1
Powder, for solutionIntramuscular; Intraperitoneal; Intravenous; Subcutaneous500 mg
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.
Patents
Not Available

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-Hybrid FT , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-Hybrid FT , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , negativeLC-MS/MSsplash10-05ne-1943110000-cfdaf16ce07341d78b59
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udl-0892110000-487a5822b41da03f0948
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0007-9621400000-9b6a525f53e7f320f714
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ikc-1771190000-39b4db7f6f66f4b9474e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0111190000-7dabe399b61bdc270ec0

Taxonomy

Description
This compound belongs to the class of organic compounds known as acetohydroxamic acids. These are organic compounds that contain a hydroxamic acid group carrying a methyl group attached to its carbon center.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Carboxylic acid derivatives
Direct Parent
Acetohydroxamic acids
Alternative Parents
Acetamides / Amino acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
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
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
acyclic desferrioxamine (CHEBI:4356) / a hydroxamate siderophore (CPD-3764)

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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transition metal ion binding
Specific Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and tra...
Gene Name
APP
Uniprot ID
P05067
Uniprot Name
Amyloid beta A4 protein
Molecular Weight
86942.715 Da
References
  1. Venti A, Giordano T, Eder P, Bush AI, Lahiri DK, Greig NH, Rogers JT: The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004 Dec;1035:34-48. [PubMed:15681799]

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. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
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 December 10, 2017 17:18