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Identification
NameGalsulfase
Accession NumberDB01279
TypeBiotech
GroupsApproved, Investigational
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 structureDb01279
Related Articles
Protein chemical formulaC2534H3851N691O719S16
Protein average weight56012.6 Da
Sequences
>Galsulfase
SGAGASRPPHLVFLLADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRS
QLLTGRYQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRKECL
PTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVATGYKNMYSTNIFT
KRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPYDFIQDKNRHHYAGMVSLMDEA
VGNVTAALKSSGLWNNTVFIFSTDNGGQTLAGGNNWPLRGRKWSLWEGGVRGVGFVASPL
LKQKGVKNRELIHISDWLPTLVKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNID
PNFVDSSPCPRNSMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQ
YNVSEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSVPVYFPA
QDPRCDPKATGVWGPWM
Download FASTA Format
Synonyms
ARSB
Arylsufatase B
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naglazymesolution5 mg/5mLintravenousBio Marin Pharmaceutical Inc.2005-06-09Not applicableUs
Naglazymesolution1 mgintravenousBiomarin Pharmaceutical Inc2014-01-01Not 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
UNII59UA429E5G
CAS number552858-79-4
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 adults and children with Mucopolysaccharidosis VI.
PharmacodynamicsMucopolysaccharide 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 actionGalsulfase 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.
Related Articles
AbsorptionNot Available
Volume of distribution

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

Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week.
ClearanceNot Available
ToxicityThere is no experience with overdose of galsulfase.
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
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.
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Online.lexi.com.login.ezproxy.library.ualberta.ca,. ‘University Of Alberta Libraries’. N.p., 2014. Web. 11 Nov. 2014.
External Links
ATC CodesA16AB08
AHFS CodesNot Available
PDB Entries
FDA labelDownload (180 KB)
MSDSNot Available
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot 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
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 ]
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Drug created on May 16, 2007 16:31 / Updated on March 14, 2016 09:59