A database of FDA approved therapeutic peptides and proteins
| This page displays user query in tabular form. |
1494 details |
| Primary information | |
|---|---|
| ThPP ID | Th1101 |
| Therapeutic Peptide/Protein Name | Galsulfase |
| Sequence | SGAGASRPPHLVFLLADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYY view full sequnce in fasta |
| Functional Classification | Ia |
| Molecular Weight | 56012.6 |
| Chemical Formula | C2534H3851N691O719S16 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | 9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week.. |
| Description | A 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/Disease | For the treatment of adults and children with Mucopolysaccharidosis VI. |
| 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. |
| Toxicity | There is no experience with overdose of galsulfase. |
| Metabolism | N.A. |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Enzyme Replacement Agents |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Dermatan sulfate,Perilipin-3 |
| Information of corresponding available drug in the market | |
| Brand Name | Naglazyme |
| Company | BioMarin |
| Brand Discription | NAGLAZYME 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 for | NAGLAZYME (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 Name | N.A. |
| Formulation | NAGLAZYME 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 Appearnce | Sterile, 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 Administration | Intravenous infusion |
| Recommended Dosage | The 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. |
| Contraindication | N.A. |
| Side Effects | Serious 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 Link | http://www.naglazyme.com/Naglazyme_Prescribing_Information.pdf |
| PubMed ID | 24764221, 24108527, 23557332, 23535281, 23244660 |
| 3-D Structure | Th1101 (View) or (Download) |