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Identification
NameIdursulfase
Accession NumberDB01271
TypeBiotech
GroupsApproved
Description

Idursulfase is a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Idursulfase is produced by recombinant DNA technology in a human cell line. Idursulfase is an enzyme that hydrolyzes the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate in the lysosomes of various cell types. Idursulfase is a 525-amino acid glycoprotein with a molecular weight of approximately 76 kilodaltons. The enzyme contains eight asparagine-linked glycosylation sites occupied by complex oligosaccharide structures. The enzyme activity of idursulfase is dependent on the post-translational modification of a specific cysteine to formylglycine.

Protein structureNo structure small
Related Articles
Protein chemical formulaC2654H4000N688O774S14
Protein average weight76000.0 Da
Sequences
>Idursulfase heavy chain
SETQANSTTDALNVLLIIVDDLRPSLGCYGDKLVRSPNIDQLASHSLLFQNAFAQQAVCA
PSRVSFLTGRRPDTTRLYDFNSYWRVHAGNFSTIPQYFKENGYVTMSVGKVFHPGISSNH
TDDSPYSWSFPPYHPSSEKYENTKTCRGPDGELHANLLCPVDVLDVPEGTLPDKQSTEQA
IQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEFQKLYPLENITLAPDPEVPDGLPPVAYN
PWMDIRQREDVQALNISVPYGPIPVDFQRKIRQSYFASVSYLDTQVGRLLSALDDLQLAN
STIIAFTSDHGWALGEHGEWAKYSNFDVATHVPLIFYVPGRTASLPEAGEKLFPYLDPFD
SASQLMEPGRQSMDLVELVSLFPTLAGLAGLQVPPRCPVPSFHVELCREGKNLLKHFRFR
DLEEDPYLPG
>Idursulfase light chain
NPRELIAYSQYPRPSDIPQWNSDKPSLKDIKIMGYSIRTIDYRYTVWVGFNPDEFLANFS
DIHAGELYFVDSDPLQDHNMYNDSQGGDLFQLLMP
Download FASTA Format
Synonyms
Alpha-L-iduronate sulfate sulfatase
Iduronate 2-sulfatase
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Elaprasesolution, concentrate6 mg/3mLintravenousShire US Manufacturing Inc.2006-07-24Not applicableUs
Elaprasesolution2 mgintravenousShire Human Genetic Therapies Inc2007-08-01Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5W8JGG2651
CAS number50936-59-9
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of Hunter syndrome in adults and children ages 5 and older.
PharmacodynamicsIdursulfase is a purified form of the lysosomal enzyme human iduronate-2-sulfatase of recombinant DNA origin. It is designed to replace the natural enzyme, increasing catabolism of certain accumulated glycosaminoglycans (GAG), which abnormally accumulate in multiple tissue types in patients with mucopolysaccharidosis II (MPS-II, or Hunter syndrome).
Mechanism of actionHunter's Syndrome is an X-linked recessive disease caused by insufficient levels of the lysosomal enzyme iduronate-2-sulfatase. This enzyme cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate. Due to the missing or defective iduronate-2-sulfatase enzyme in patients with Hunter's Syndrome, GAG progressively accumulate in the lysosomes of a variety of cells, leading to cellular engorgement, organomegaly, tissue destruction and organ system dysfunction. Treatment of Hunter's Syndrome patients with idursulfase provides exogenous enzyme for uptake into cellular lysosomes. Targeting of idursulfase to the lysosome occurs by endocytosis from the cell surface. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow specific binding of the enzymes to the M6P receptors on the cell surface, leading to cellular internalization of the enzyme, targeting to intracellular lysosomes and subsequent catabolism of accumulated GAG.
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AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life44 ± 19 minutes
Clearance
  • 3 mL/min/kg [Patients (7.7 – 27 years) with Hunter syndrome with treatment week 1(0.5 mg/kg ELAPRASE administered weekly as a 3-hour infusion)]
  • 3.4 mL/min/kg [patients (7.7 – 27 years) with Hunter syndrome with treatment week 27 (0.5 mg/kg ELAPRASE administered weekly as a 3-hour infusion)]
ToxicityThere is no experience with overdosage of Idursulfase in humans. Single intravenous doses of idursulfase up to 20 mg/kg were not lethal in male rats and cynomolgus monkeys (approximately 6.5 and 13 times, respectively, of the recommended human dose based on body surface area) and there were no clinical signs of toxicity.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionintravenous2 mg
Solution, concentrateintravenous6 mg/3mL
Prices
Unit descriptionCostUnit
Elaprase 6 mg/3 ml vial1051.28USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Garcia AR, DaCosta JM, Pan J, Muenzer J, Lamsa JC: Preclinical dose ranging studies for enzyme replacement therapy with idursulfase in a knock-out mouse model of MPS II. Mol Genet Metab. 2007 Jun;91(2):183-90. Epub 2007 Apr 24. [PubMed:17459751 ]
  2. Zareba G: Idursulfase in Hunter syndrome treatment. Drugs Today (Barc). 2007 Nov;43(11):759-67. doi: 10.1358/dot.2007.43.11.1157619. [PubMed:18174963 ]
  3. Clarke LA: Idursulfase for the treatment of mucopolysaccharidosis II. Expert Opin Pharmacother. 2008 Feb;9(2):311-7. doi: 10.1517/14656566.9.2.311 . [PubMed:18201153 ]
  4. Burrow TA, Leslie ND: Review of the use of idursulfase in the treatment of mucopolysaccharidosis II. Biologics. 2008 Jun;2(2):311-20. [PubMed:19707363 ]
  5. Scarpa M: Mucopolysaccharidosis Type II . 1993;():. [PubMed:20301451 ]
  6. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J: Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. [PubMed:18038146 ]
External Links
ATC CodesA16AB09
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
yes
References
  1. Burrow TA, Leslie ND: Review of the use of idursulfase in the treatment of mucopolysaccharidosis II. Biologics. 2008 Jun;2(2):311-20. [PubMed:19707363 ]
  2. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J: Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. [PubMed:18038146 ]
  3. Garcia AR, Pan J, Lamsa JC, Muenzer J: The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). J Inherit Metab Dis. 2007 Nov;30(6):924-34. Epub 2007 Sep 16. [PubMed:17876721 ]
2. Heparan sulfate
Kind
Small molecule
Organism
Human
Pharmacological action
yes
References
  1. Burrow TA, Leslie ND: Review of the use of idursulfase in the treatment of mucopolysaccharidosis II. Biologics. 2008 Jun;2(2):311-20. [PubMed:19707363 ]
  2. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J: Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. [PubMed:18038146 ]
  3. Garcia AR, Pan J, Lamsa JC, Muenzer J: The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). J Inherit Metab Dis. 2007 Nov;30(6):924-34. Epub 2007 Sep 16. [PubMed:17876721 ]
Kind
Protein
Organism
Human
Pharmacological action
no
General Function:
Not Available
Specific Function:
Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network.
Gene Name:
PLIN3
Uniprot ID:
O60664
Molecular Weight:
47074.665 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Clarke LA: Idursulfase for the treatment of mucopolysaccharidosis II. Expert Opin Pharmacother. 2008 Feb;9(2):311-7. doi: 10.1517/14656566.9.2.311 . [PubMed:18201153 ]
  4. Burrow TA, Leslie ND: Review of the use of idursulfase in the treatment of mucopolysaccharidosis II. Biologics. 2008 Jun;2(2):311-20. [PubMed:19707363 ]
  5. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J: Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. Epub 2007 Nov 23. [PubMed:18038146 ]
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Drug created on May 16, 2007 14:17 / Updated on March 14, 2016 09:59