Primary information |
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ThPP ID | Th1085 |
Therapeutic Peptide/Protein Name | Agalsidase beta |
Sequence | LDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGW view full sequnce in fasta |
Functional Classification | Ia |
Molecular Weight | 45351.6 |
Chemical Formula | C2029H3080N544O587S27 |
Isoelectric Point | 5.17 |
Hydrophobicity | -0.307 |
Melting Point (℃) | N.A. |
Half Life | 45-102 min |
Description | Recombinant human alpha-galactosidase-A produced in CHO cells. The mature protein comprises 2 subunits of 398 residues. |
Indication/Disease | For treatment of Fabry's disease (alpha-galactosidase A deficiency) |
Pharmacodynamics | Used in the treatment of Fabry disease, an X-linked genetic disorder of glycosphingolipid metabolism. The disease is characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, which leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents. Fabrazyme is intended to provide an exogenous source of alpha-galactosidase A and to limit the accumulation of these glycolipids in the tissues. Studies show unconclusive evidence for the clinical efficacy of either agalasidase alfa or agalasidase beta in preventing morbidity. |
Mechanism of Action | Alpha-galactosidase A catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other a-galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide and blood group B substances to ceramide dihexoside and galactose. |
Toxicity | N.A. |
Metabolism | N.A. |
Absorption | N.A. |
Volume of Distribution | N.A. |
Clearance | 4.1 ± 1.2 mL/min/kg [adult patients with Fabry disease,0.3 mg/kg, 1 infusion] 4.6 ± 2.2 mL/min/kg [adult patients with Fabry disease, 0.3 mg/kg, 5 infusions] 2.1 ± 0.7 mL/min/kg [adult patients with Fabry disease, 1 mg/kg, 1 infusion] 3.2 ± 2.6 mL/min/kg [adult patients with Fabry disease, 1 mg/kg, 5 infusions] 0.8 ± 0.3 mL/min/kg [adult patients with Fabry disease, 3 mg/kg, 1 infusion] 0.8 ± 0.4 mL/min/kg [adult patients with Fabry disease, 3 mg/kg, 5 infusions] 1.8 ± 0.8 mL/min/kg [Pedi |
Categories | Enzyme Replacement Agents |
Patents Number | CA2265464 |
Date of Issue | 27/06/11 |
Date of Expiry | 13/09/21 |
Drug Interaction | N.A. |
Target | N.A. |
Information of corresponding available drug in the market |
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Brand Name | Fabrazyme |
Company | Genzyme Corp |
Brand Discription | Fabrazyme (agalsidase beta) is a recombinant human α-galactosidase A enzyme with the same amino acid sequence as the native enzyme. Purified agalsidase beta is a homodimeric glycoprotein with a molecular weight of approximately 100 kD. The mature protein is comprised of two subunits of 398 amino acids (approximately 51 kD), each of which contains three N-linked glycosylation sites. α-galactosidase A catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other α-galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide and blood group B substances to ceramide dihexoside and galactose. The specific activity of Fabrazyme (agalsidase beta) is approximately 70 U/mg (one unit is defined as the amount of activity that results in the hydrolysis of 1 rjmoie of a synthetic substrate, p-nitrophenyl-α-D-galactopyranoside, per minute under the assay conditions).Fabrazyme (agalsidase beta) is produced by recombinant DNA technology in a Chinese Hamster Ovary mammalian cell expression system. |
Prescribed for | Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. |
Chemical Name | N.A. |
Formulation | Each 5 mg vial contains 5.5 mg of agalsidase beta as well as 33.0 mg mannitol, 3.0 mg sodium phosphate monobasic monohydrate, and 8.8 mg sodium phosphate dibasic heptahydrate. Following reconstitution as directed, 5 mg of agalsidase beta (1 mL) may be extracted from each 5 mg vial. |
Physcial Appearnce | Sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with Sterile Water for Injection, uSp. Each 35 mg vial contains 37 mg of agalsidase beta as well as 222 mg mannitol, 20.4 mg sodium phosphate monobasic monohydrate, and 59.2 mg sodium phosphate dibasic heptahydr |
Route of Administration | N.A. |
Recommended Dosage | N.A. |
Contraindication | This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. |
Side Effects | difficulty breathing; closing of the throat; hives; rash; itching; fever; shaking; chest tightness; high or low blood pressure; fast heartbeats; muscle pain; stomach pain; nausea or vomiting; dizziness; numbness or tingling; and headache have occurred upon injection of agalsidase beta in many patients. Most patients treated with agalsidase beta develop antibodies to agalsidase beta and many will develop symptoms of an infusion reaction. A slow rate of injection of the medication and pretreatment with other medications may decrease. |
Useful Link | http://www.rxlist.com/fabrazyme-drug.htm |
PubMed ID | 19852524, 25010055, 24850233, 24718841, 24408305 |
3-D Structure | Th1085 (View) or (Download) |