Laronidase

Identification

Name
Laronidase
Accession Number
DB00090  (BTD00008, BIOD00008)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Description

Human recombinant alpha-L-iduronidase, 628 residues (mature form), produced by recombinant DNAtechnology in a Chinese hamster ovary cell line. Laronidase is a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to a polymorphic form of human a-L-iduronidase. It contains 6 N-linked oligosaccharide modification sites.

Protein structure
Db00090
Protein chemical formula
C3160H4848N898O881S12
Protein average weight
69899.4 Da
Sequences
>DB00090 sequence
APHLVQVDAARALWPLRRFWRSTGFCPPLPHSQADQYVLSWDQQLNLAYVGAVPHRGIKQ
VRTHWLLELVTTRGSTGRGLSYNFTHLDGYLDLLRENQLLPGFELMGSASGHFTDFEDKQ
QVFEWKDLVSSLARRYIGRYGLAHVSKWNFETWNEPDHHDFDNVSMTMQGFLNYYDACSE
GLRAASPALRLGGPGDSFHTPPRSPLSWGLLRHCHDGTNFFTGEAGVRLDYISLHRKGAR
SSISILEQEKVVAQQIRQLFPKFADTPIYNDEADPLVGWSLPQPWRADVTYAAMVVKVIA
QHQNLLLANTTSAFPYALLSNDNAFLSYHPHPFAQRTLTARFQVNNTRPPHVQLLRKPVL
TAMGLLALLDEEQLWAEVSQAGTVLDSNHTVGVLASAHRPQGPADAWRAAVLIYASDDTR
AHPNRSVAVTLRLRGVPPGPGLVYVTRYLDNGLCSPDGEWRRLGRPVFPTAEQFRRMRAA
EDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHVCARPEKPPGQVTRLRALPLTQGQLVLV
WSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPSTFNLFVFSPDTGAVSGSYRVRALDYWA
RPGPFSDPVPYLEVPVPRGPPSPGNP
Download FASTA Format
Synonyms
  • Alpha-L-iduronidase precursor
  • Laronidasa
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AldurazymeInjection, solution, concentrate100 U/mlIntravenousGenzyme Europe Bv2003-06-10Not applicableEu
AldurazymeSolution0.58 mgIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2004-08-12Not applicableCanada
AldurazymeInjection, solution, concentrate100 U/mlIntravenousGenzyme Europe Bv2003-06-10Not applicableEu
AldurazymeInjection, solution, concentrate2.9 mg/5mLIntravenousGenzyme Corporation2003-04-30Not applicableUs
AldurazymeInjection, solution, concentrate100 U/mlIntravenousGenzyme Europe Bv2003-06-10Not applicableEu
Categories
UNII
WP58SVM6R4
CAS number
210589-09-6

Pharmacology

Indication

For the treatment of mucopolysaccharidosis

Associated Conditions
Pharmacodynamics

Laronidase is used to treat mucopolysaccharide storage disorders (specifically mucopolysaccharidosis 1 or Hurlers syndrome) caused by deficiencies of alpha-L-iduronidase. Reduced or absent a-L-iduronidase activity results in the accumulation of the GAG substrates, dermatan sulfate and heparan sulfate, throughout the body and leads to widespread cellular, tissue, and organ dysfunction.

Mechanism of action

Laronidase catalyses the hydrolysis of terminal alpha-L-iduronic acid residues of dermatan sulfate and heparin sulfate.

TargetActionsOrganism
AIduronic acid
other/unknown
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

1.5-3.6 hrs

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
  1. Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF: Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009 Jan;123(1):229-40. doi: 10.1542/peds.2007-3847. [PubMed:19117887]
  2. Landry Y, Gies JP: Drugs and their molecular targets: an updated overview. Fundam Clin Pharmacol. 2008 Feb;22(1):1-18. doi: 10.1111/j.1472-8206.2007.00548.x. [PubMed:18251718]
External Links
UniProt
P35475
Genbank
M74715
PubChem Substance
46505612
ChEMBL
CHEMBL1201595
PharmGKB
PA164776670
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Laronidase
ATC Codes
A16AB05 — Laronidase
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (43.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentHurler's Syndrome2
1TerminatedTreatmentHurler-Scheie Syndrome / Lysosomal Storage Diseases / Mucopolysaccharidosis V / Spinal Cord Compression / Type 1 Mucopolysaccharidosis1
1TerminatedTreatmentLysosomal Storage Diseases / Spinal Cord Compression / Type 1 Mucopolysaccharidosis1
1, 2CompletedTreatmentType 1 Mucopolysaccharidosis1
2CompletedTreatmentHurler's Syndrome / Hurler-Scheie Syndrome / Mucopolysaccharidosis V / Type 1 Mucopolysaccharidosis1
2CompletedTreatmentHurler's Syndrome / Type 1 Mucopolysaccharidosis1
3CompletedTreatmentHurler's Syndrome / Hurler-Scheie Syndrome / Mucopolysaccharidosis V / Type 1 Mucopolysaccharidosis2
3CompletedTreatmentHurler-Scheie Syndrome / Hurlers Syndrome / Type 1 Mucopolysaccharidosis1
4CompletedTreatmentHurler's Syndrome / Hurler-Scheie Syndrome / Mucopolysaccharidosis V / Type 1 Mucopolysaccharidosis2
4RecruitingTreatmentHurler's Syndrome / Hurler-Scheie Syndrome / Scheie / Type 1 Mucopolysaccharidosis1
Not AvailableCompletedTreatmentCognitive Decline / Hurler-Scheie Syndrome / Lysosomal Storage Diseases / Mucopolysaccharidosis V / Type 1 Mucopolysaccharidosis1
Not AvailableEnrolling by InvitationTreatmentCognitive Decline / Type 1 Mucopolysaccharidosis1
Not AvailableTerminatedNot AvailableHurler's Syndrome / MPS I / Mucopolysaccharidosis Type IH1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • BioMarin Pharmaceuticals Inc.
  • Genzyme Inc.
  • Hollister-Stier Laboratories LLC
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous100 U/ml
Injection, solution, concentrateIntravenous2.9 mg/5mL
SolutionIntravenous0.58 mg
Prices
Unit descriptionCostUnit
Aldurazyme 2.9 mg/5 ml vial168.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.300Not Available
isoelectric point9.09Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
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. Kloska A, Bohdanowicz J, Konopa G, Tylki-Szymnska A, Jakobkiewicz-Banecka J, Czartoryska B, Liberek A, Wegrzyn A, Wegrzyn G: Changes in hair morphology of mucopolysaccharidosis I patients treated with recombinant human alpha-L-iduronidase (laronidase, Aldurazyme). Am J Med Genet A. 2005 Dec 15;139(3):199-203. [PubMed:16283671]
  4. Bach G, Eisenberg F Jr, Cantz M, Neufeld EF: The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2134-8. [PubMed:4269173]
  5. Freeman C, Hopwood JJ: Human alpha-L-iduronidase. Catalytic properties and an integrated role in the lysosomal degradation of heparan sulphate. Biochem J. 1992 Mar 15;282 ( Pt 3):899-908. [PubMed:1554373]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:38