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
- 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)
- N-acetylgalactosamine-4-sulfatase, recombinant human
Pharmacology
- Indication
For the treatment of adults and children with Mucopolysaccharidosis VI.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Mucopolysaccharidosis vi •••••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ADermatan sulfate Not Available Humans APerilipin-3 Not Available Humans - 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
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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
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Naglazyme Solution 5 mg/5mL Intravenous BioMarin Pharmaceutical Inc. 2005-06-09 Not applicable US Naglazyme Injection, solution, concentrate 1 mg/ml Intravenous Biomarin International Limited 2016-09-08 Not applicable EU Naglazyme Solution 1 mg / mL Intravenous BioMarin Pharmaceutical Inc. 2014-01-01 Not applicable Canada Naglazyme Injection, solution, concentrate 1 mg/ml Intravenous Biomarin International Limited 2016-09-08 Not applicable EU
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
- External Links
- PubChem Substance
- 46509151
- 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
Phase Status Purpose Conditions Count 4 Completed Prevention Mucopolysaccharidosis Type VI 1 1 Recruiting Treatment Gaucher Disease, Type II / Gaucher Disease, Type III / Infantile-onset Pompe Disease / MPS VI / Mucopolysaccharidosis Type II (MPS II) / Mucopolysaccharidosis Type IVA / Mucopolysaccharidosis Type VII / Myocardial Perfusion Imaging / Wolman's Disease 1 Not Available Terminated Treatment Mucopolysaccharidosis Type VI 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- BioMarin Pharmaceuticals Inc.
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 1 MG/ML Solution Intravenous 1 mg / mL Solution Intravenous 5 mg/5mL Injection, solution Intravenous Solution, concentrate Intravenous 5 mg - Prices
Unit description Cost Unit Naglazyme 5 mg/5 ml vial 391.2USD 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
References
- 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]
- 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]
- 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
- 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]
- 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 at May 16, 2007 22:31 / Updated at June 02, 2023 02:07