Galsulfase

Identification

Summary

Galsulfase is a recombinant human enzyme used as replacement enzyme therapy for the treatment of of adults and children with Mucopolysaccharidosis VI, a rare genetic disorder caused by a deficiency of a lysosomal enzyme.

Brand Names
Naglazyme
Generic Name
Galsulfase
DrugBank Accession Number
DB01279
Background

Galsufase is a variant form of the polymorphic human enzyme N-acetylgalactosamine 4-sulfatase of recombinant DNA origin. Galsulfase is a glycoprotein with a molecular weight of approximately 56 kD. The recombinant protein is comprised of 495 amino acids and contains six asparagine-linked glycosylation sites, four of which carry a bis mannose-6-phosphate manose7 oligosaccharide for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue Ca-formylglycine, which is required for enzyme activity and is conserved in all members of the sulfatase enzyme family.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Structure
Db01279
Protein Chemical Formula
C2534H3851N691O719S16
Protein Average Weight
56012.6 Da
Sequences
>Galsulfase
SGAGASRPPHLVFLLADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRS
QLLTGRYQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRKECL
PTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVATGYKNMYSTNIFT
KRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPYDFIQDKNRHHYAGMVSLMDEA
VGNVTAALKSSGLWNNTVFIFSTDNGGQTLAGGNNWPLRGRKWSLWEGGVRGVGFVASPL
LKQKGVKNRELIHISDWLPTLVKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNID
PNFVDSSPCPRNSMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQ
YNVSEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSVPVYFPA
QDPRCDPKATGVWGPWM
Download FASTA Format
Synonyms
  • Arylsulfatase B galsulfase
  • Galsulfasa
  • Galsulfase
  • Galsulfase (genetical recombination)

Pharmacology

Indication

For the treatment of adults and children with Mucopolysaccharidosis VI.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. Galsulfase is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.

Mechanism of action

Galsulfase supplies recombinant-engineered galsulfase, a normal variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase. It is a lysosomal hydrolase that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of GAG chondroitin 4-sulfate and dermatan sulfate. Increased catabolism of GAG in turn reduces systemic dermatan sulfate accumulation, thereby reducing the primary symptoms of MPS VI.

TargetActionsOrganism
ADermatan sulfateNot AvailableHumans
APerilipin-3Not AvailableHumans
Absorption

Not Available

Volume of distribution

Week 1: 56-323 mL/kg and 59-2799 mL/kg by week 24

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week.

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

There is no experience with overdose of galsulfase.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
No interactions found.
Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NaglazymeInjection, solution, concentrate1 mg/mlIntravenousBiomarin International Limited2016-09-08Not applicableEU flag
NaglazymeSolution5 mg/5mLIntravenousBioMarin Pharmaceutical Inc.2005-06-09Not applicableUS flag
NaglazymeInjection, solution, concentrate1 mg/mlIntravenousBiomarin International Limited2016-09-08Not applicableEU flag
NaglazymeSolution1 mg / mLIntravenousBiomarin International Limited2014-01-01Not applicableCanada flag

Categories

ATC Codes
A16AB08 — Galsulfase
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
59UA429E5G
CAS number
552858-79-4

References

General References
Not Available
PubChem Substance
46509151
RxNav
578033
ChEMBL
CHEMBL1201822
Therapeutic Targets Database
DAP001290
PharmGKB
PA164746235
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Arylsulfatase_B
FDA label
Download (180 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionMucopolysaccharidosis VI1
1RecruitingTreatmentGaucher Disease, Type 3 / MPS II / MPS IVA / MPS VI / MPS VII / Myocardial Perfusion Imaging / Pompe Disease (Infantile-Onset) / Type 2 Gaucher Disease / Wolman's Disease1
Not AvailableTerminatedTreatmentMucopolysaccharidosis VI1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • BioMarin Pharmaceuticals Inc.
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous1 MG/ML
SolutionIntravenous1 mg / mL
SolutionIntravenous5 mg/5mL
Injection, solutionIntravenous
Solution, concentrateIntravenous5 mg
Prices
Unit descriptionCostUnit
Naglazyme 5 mg/5 ml vial391.2USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
References
  1. Tifft C, Proud V, Levy P, DeMarco K, Nicely H, Turbeville S: Enzyme replacement therapy in the home setting for mucopolysaccharidosis VI: a survey of patient characteristics and physicians' early findings in the United States. J Infus Nurs. 2009 Jan-Feb;32(1):45-52. doi: 10.1097/NAN.0b013e31819228ee. [Article]
  2. Dogan M, Cesur Y, Peker E, Oner AF, Dogan SZ: Thrombocytopenia associated with galsulfase treatment. Hum Exp Toxicol. 2011 Jul;30(7):768-71. doi: 10.1177/0960327110379023. Epub 2010 Jul 29. [Article]
  3. White JT, Argento Martell L, Prince WS, Boyer R, Crockett L, Cox C, Van Tuyl A, Aguilera A, Foehr E: Comparison of neutralizing antibody assays for receptor binding and enzyme activity of the enzyme replacement therapeutic Naglazyme (galsulfase). AAPS J. 2008 Sep;10(3):439-49. doi: 10.1208/s12248-008-9048-1. Epub 2008 Aug 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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
Uniprot Name
Perilipin-3
Molecular Weight
47074.665 Da
References
  1. 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. [Article]
  2. White JT, Argento Martell L, Prince WS, Boyer R, Crockett L, Cox C, Van Tuyl A, Aguilera A, Foehr E: Comparison of neutralizing antibody assays for receptor binding and enzyme activity of the enzyme replacement therapeutic Naglazyme (galsulfase). AAPS J. 2008 Sep;10(3):439-49. doi: 10.1208/s12248-008-9048-1. Epub 2008 Aug 16. [Article]

Drug created on May 16, 2007 22:31 / Updated on October 22, 2021 23:18