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Identification
Name Deferasirox
Accession Number DB01609
Type small molecule
Groups approved
Description

Deferasirox is an oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Deferasiroxum [inn-latin]
ICL 670
Salts Not Available
Brand names
Name Company
Exjade
Brand mixtures Not Available
Categories
  • Iron Chelating Agents
CAS number 201530-41-8
Weight Average: 373.3615
Monoisotopic: 373.106255983
Chemical Formula C21H15N3O4
InChI Key InChIKey=BOFQWVMAQOTZIW-UHFFFAOYSA-N
InChI
InChI=1S/C21H15N3O4/c25-17-7-3-1-5-15(17)19-22-20(16-6-2-4-8-18(16)26)24(23-19)14-11-9-13(10-12-14)21(27)28/h1-12,25-26H,(H,27,28)
Plain Text
IUPAC Name
4-[bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid
SMILES
OC(=O)C1=CC=C(C=C1)N1N=C(N=C1C1=CC=CC=C1O)C1=CC=CC=C1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminobenzoates
Substructures
  • Triazolidines
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Benzene and Derivatives
  • Aminobenzoates
  • Carboxylic Acids and Derivatives
  • Isoprenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Ketenes and Derivatives
  • Hydrazine Derivatives
  • Benzoyl Derivatives
  • Phenylhydrazines
  • Anilines
  • Ketones
Pharmacology
Indication For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.
Pharmacodynamics Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.
Mechanism of action Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys.
Absorption The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose.
Volume of distribution
  • 14.37 ± 2.69 L
Protein binding Deferasirox is highly (~99%) protein bound almost exclusively to serum albumin.
Metabolism Hepatic. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion.
Route of elimination Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% of the administered dose).
Half life The mean elimination half-life ranged from 8 to 16 hours following oral administration.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Tablet, for suspension Oral
Prices
Unit description Cost Unit
Exjade 500 mg tablet 78.61 USD tablet
Exjade 250 mg tablet 39.3 USD tablet
Exjade 125 mg tablet 19.65 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6465504 1999-04-05 2019-04-05
United States 6596750 1997-06-24 2017-06-24
Canada 2255951 2006-10-10 2017-06-24
Properties
State solid
Experimental Properties
Property Value Source
melting point 116-117 °C Not Available
water solubility 0.038 mg/mL at 37 °C YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 3.52 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 3.43e-02 g/l ALOGPS
logP 4.01 ALOGPS
logP 4.74 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 4.55 ChemAxon
pKa (strongest basic) 0.19 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 108.47 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 125.32 ChemAxon
polarizability 38.52 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D03669 Link_out
PubChem Compound 5493381 Link_out
PubChem Substance 46506791 Link_out
ChemSpider 4591431 Link_out
PharmGKB PA164760843 Link_out
Drug Product Database 1926756 Link_out
RxList http://www.rxlist.com/cgi/generic/exjade.htm Link_out
Drugs.com http://www.drugs.com/cdi/deferasirox.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Deferasirox Link_out
ATC Codes
  • V03AC03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Aluminium Possible physicochemical interaction
Bivalirudin Anticoagulants increase the risk for gastrointestinal ulceration/irritation and/or GI bleeding. If these two agents must be used, patients need to be closely monitored for signs and symptoms of GI toxicity.
Food Interactions
  • Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion, respectively.
  • Food causes inconsistent increases in the bioavailability of this product.
  • Tablets should be completely dispersed in water, orange juice or apple juice and the resulting suspension should be ingested immediately (after swallowing the suspension, any residue should be resuspended in a small volume of liquid and swallowed).
  • Tablets should be taken on an empty stomach at least 30 minutes before a meal, preferably at the same time everyday.
Targets

1. Iron

Pharmacological action: yes
Actions: chelator

References:
  1. Wang T, Gao C, Chen BA: [Deferasirox—a new oral iron chelator—review]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Oct;18(5):1359-64. Pubmed
  2. Ibrahim AS, Spellberg B, Edwards J Jr: Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis. 2008 Dec;21(6):620-5. Pubmed
  3. Devanur LD, Evans RW, Evans PJ, Hider RC: Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy. Biochem J. 2008 Jan 15;409(2):439-47. Pubmed
  4. Lebitasy M, Ampe E, Hecq JD, Karmani L, Nick H, Galanti L: Ability of deferasirox to bind iron during measurement of iron. Clin Chem Lab Med. 2010 Mar;48(3):427-9. Pubmed
  5. Yang LP, Keam SJ, Keating GM: Deferasirox : a review of its use in the management of transfusional chronic iron overload. Drugs. 2007;67(15):2211-30. Pubmed
  6. Choudhry VP, Naithani R: Current status of iron overload and chelation with deferasirox. Indian J Pediatr. 2007 Aug;74(8):759-64. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Skerjanec A, Wang J, Maren K, Rojkjaer L: Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers. J Clin Pharmacol. 2010 Feb;50(2):205-13. Epub 2009 Nov 25. Pubmed
Comments
Drug created on August 29, 2007 13:21 / Updated on February 08, 2013 16:20