==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

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1494 details
Primary information
ThPP IDTh1101
Therapeutic Peptide/Protein NameGalsulfase
SequenceSGAGASRPPHLVFLLADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYY view full sequnce in fasta
Functional ClassificationIa
Molecular Weight56012.6
Chemical FormulaC2534H3851N691O719S16
Isoelectric PointN.A.
HydrophobicityN.A.
Melting Point (℃)N.A.
Half Life9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week..
DescriptionA recombinant variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase. It is a glycoprotein with a molecular weight of approximately 56 kD and comprises 495 amino acids. It contains 6 N-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate manose7 oligosaccharide for specific cellular recognition. It requires Ca-formylglycine for its catalytic activity. This residue is a post-translational modification of Cys53 and conserved in all members of the sulfatase enzyme family.
Indication/DiseaseFor 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.
ToxicityThere is no experience with overdose of galsulfase.
MetabolismN.A.
AbsorptionN.A.
Volume of DistributionN.A.
ClearanceN.A.
CategoriesEnzyme Replacement Agents
Patents NumberN.A.
Date of IssueN.A.
Date of ExpiryN.A.
Drug InteractionN.A.
TargetDermatan sulfate,Perilipin-3
Information of corresponding available drug in the market
Brand NameNaglazyme
CompanyBioMarin
Brand DiscriptionNAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan N–acetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N–acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitin 4-sulfate and dermatan sulfate. Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine-linked glycosylation sites, four of which carry a bis-mannose–6–phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Cα-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4-methylumbelliferone and free sulfate per minute at 37°C.
Prescribed forNAGLAZYME (galsulfase) is indicated for patients with Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity.
Chemical NameN.A.
FormulationNAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.
Physcial AppearnceSterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration
Route of AdministrationIntravenous infusion
Recommended DosageThe recommended dosage regimen of NAGLAZYME is 1 mg per kg of body weight administered once weekly as an Intravenous infusion. Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion.
ContraindicationN.A.
Side EffectsSerious adverse reactions experienced in this trial include apnea, pyrexia, and respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions requiring interventions were infusion reactions.
Useful Linkhttp://www.naglazyme.com/Naglazyme_Prescribing_Information.pdf
PubMed ID24764221, 24108527, 23557332, 23535281, 23244660
3-D StructureTh1101 (View) or (Download)