Galsulfase

Identification

Name
Galsulfase
Accession Number
DB01279
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Description

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.

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
  • ARSB
  • Arylsufatase B
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NaglazymeSolution1 mgIntravenousBiomarin International Limited2014-01-01Not applicableCanada
NaglazymeInjection, solution, concentrate1 mg/mlIntravenousBio Marin Europe Ltd.2006-01-24Not applicableEu
NaglazymeInjection, solution, concentrate1 mg/mlIntravenousBio Marin Europe Ltd.2006-01-24Not applicableEu
NaglazymeSolution5 mg/5mLIntravenousBiomarin International Limited2005-06-09Not applicableUs
Categories
UNII
59UA429E5G
CAS number
552858-79-4

Pharmacology

Indication

For the treatment of adults and children with Mucopolysaccharidosis VI.

Structured Indications
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 AvailableHuman
APerilipin-3Not AvailableHuman
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
Toxicity

There is no experience with overdose of galsulfase.

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
Not Available
External Links
PubChem Substance
46509151
ChEMBL
CHEMBL1201822
Therapeutic Targets Database
DAP001290
PharmGKB
PA164746235
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Galsulfase
ATC Codes
A16AB08 — Galsulfase
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (180 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionMucopolysaccharidosis VI1
Not AvailableActive Not RecruitingTreatmentMucopolysaccharidosis VI1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous1 mg/ml
SolutionIntravenous1 mg
SolutionIntravenous5 mg/5mL
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

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
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. [PubMed:19142150]
  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. [PubMed:20670992]
  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. [PubMed:18709516]
Kind
Protein
Organism
Human
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. [PubMed:17016423]
  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. [PubMed:18709516]

Drug created on May 16, 2007 16:31 / Updated on January 14, 2018 10:04