Identification
NameAlglucosidase alfa
Accession NumberDB01272
TypeBiotech
GroupsApproved
Description

Aglucosidase alfa consists of the human enzyme acid alpha-glucosidase (GAA) which is essential for the degradation of glygogen to glucose in lysosomes. It is encoded by the most predominant of nine observed haplotypes of this gene. Aglucosidase alfa is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of a-1,4- and a-1,6- glycosidic linkages of lysosomal glycogen. Structurally, Alglucosidase alfa is a glycoprotein with a calculated mass of 98,008 daltons for the 883 residue mature polypeptide chain, and a total mass of approximately 109,000 daltons, including carbohydrates. It is used for the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.

Protein structureDb01272
Related Articles
Protein chemical formulaC4435H6739N1175O1279S32
Protein average weight105270.802 Da
Sequences
>Alglucosidase alfa
AHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGAQMGQPWCFF
PPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLHFTIKDPANR
RYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLFFADQFLQLS
TSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLALEDGGSAHG
VFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGYPFMPPYWGL
GFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDGFRDFPAMVQ
ELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKVWPGSTAFPD
FTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELENPPYVPGVVG
GTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISRSTFAGHGRY
AGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVRWTQLGAFYP
FMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAGETVARPLFL
EFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPVEALGSLPPP
PAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQPMALAVALTK
GGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQLQKVTVLGV
ATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
Download FASTA Format
Synonyms
Acid maltase
Acid-alpha glucosidase
Aglucosidase alfa
Aglucosidase alpha
alpha-1,4-glucosidase
Alpha-glucosidase
Lysosomal Alpha-Glucosidase
External IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LumizymeInjection, powder, for solution5 mg/mLIntravenousGenzyme Corporation2010-05-24Not applicableUs
MyozymeInjection, powder, lyophilized, for solution5 mg/mLIntravenousGenzyme Corporation2010-06-19Not applicableUs
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEu
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEu
MyozymePowder, for solution50 mgIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2006-12-06Not applicableCanada
MyozymeInjection, powder, for solution50 mgIntravenousGenzyme Europe Bv2006-03-29Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIDTI67O9503
CAS number420784-05-0
Pharmacology
Indication

For the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.

Structured Indications
Pharmacodynamics

Pompe disease (glycogen storage disease type II, GSD II, glycogenosis type II, acid maltase deficiency) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. In the infantile-onset form, Pompe disease results in intralysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, and hepatic tissues, leading to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function. In the juvenile- and adult-onset forms, intralysosomal accumulation of glycogen is limited primarily to skeletal muscle, resulting in progressive muscle weakness. Death in all forms is usually related to respiratory failure. Alglucosidase alfa provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.

Mechanism of action

Alglucosidase alfa is designed to act as an exogenous source of GAA, acting to correct GAA deficiency that is the hallmark of Pompe disease. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen. Specifically, it hydrolyses alpha-1,4-glucose bonds.

TargetKindPharmacological actionActionsOrganismUniProt ID
Cation-dependent mannose-6-phosphate receptorProteinyes
binder
HumanP20645 details
GlycogenGroupyes
cleavage
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distribution
  • 96 ± 16 mL/kg [20 mg/kg dose]
  • 119 ± 28 mL/kg [40 mg/kg dose]
Protein bindingNot Available
MetabolismNot Available
Route of elimination

Via kidney and liver

Half life

2.3 ± 0.4 hours.

Clearance
  • 25+/- 4 mL/hr/kg [4-hour IV infusion of 20 mg/kg]
Toxicity

There have been no reports of overdose with alglucosidase alfa.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions No interactions found.
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, Leslie N, Levine J, Spencer C, McDonald M, Li J, Dumontier J, Halberthal M, Chien YH, Hopkin R, Vijayaraghavan S, Gruskin D, Bartholomew D, van der Ploeg A, Clancy JP, Parini R, Morin G, Beck M, De la Gastine GS, Jokic M, Thurberg B, Richards S, Bali D, Davison M, Worden MA, Chen YT, Wraith JE: Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007 Jan 9;68(2):99-109. Epub 2006 Dec 6. [PubMed:17151339 ]
External Links
ATC CodesA16AB07 — Alglucosidase alfa
AHFS Codes
  • 44:00.00
PDB EntriesNot Available
FDA labelDownload (1.11 MB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II / Glycogenosis 2 / Pompe's Disease1
1, 2RecruitingTreatmentPompe's Disease1
2CompletedTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II (GSD-II) / Glycogenosis 2 / Pompe Disease (Late-Onset)1
2CompletedTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II / Glycogenosis 2 / Pompe's Disease1
2CompletedTreatmentGlycogen Storage Disease Type II GSD II / Pompe Disease Late-Onset1
2CompletedTreatmentGlycogen Storage Disease Type II / Pompe Disease Infantile-Onset1
2Not Yet RecruitingTreatmentGlycogen Storage Disease Type II-Pompe's Disease1
2, 3CompletedTreatmentGlycogen Storage Disease Type II2
3CompletedTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II (GSD-II) / Glycogenosis 2 / Pompe Disease (Late-Onset)2
3RecruitingTreatmentGlycogen Storage Disease Type II-Pompe's Disease1
4Active Not RecruitingTreatmentAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II (GSD-II) / Pompe's Disease1
4CompletedTreatmentAcid Maltase Deficiency (AMD) / Glycogen Storage Disease Type II (GSD-II) / Glycogenesis Type II / Pompe Disease (Late-Onset)1
4CompletedTreatmentGlycogen Storage Disease Type II (GSD II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe Disease (Late-Onset)1
4CompletedTreatmentGlycogen Storage Disease Type II (GSD-II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe's Disease1
4CompletedTreatmentGlycogen Storage Disease Type II / Pompe's Disease1
4RecruitingNot AvailableGlycogen Storage Disease Type II (GSD-II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe Disease (Late-Onset)1
4RecruitingNot AvailableGlycogen Storage Disease / Pompe's Disease1
4RecruitingOtherAcid Maltase Deficiency (AMD) / Glycogen Storage Disease Type II (GSD II) / Glycogenesis 2 / Pompe Disease (Late-Onset)1
4RecruitingTreatmentGlycogen Storage Disease Type II (GSD-II) / Glycogenesis 2 Acid Maltase Deficiency / Pompe's Disease1
4TerminatedTreatmentAcid Maltase Deficiency (AMD) / Glycogen Storage Disease Type II (GSD II) / Glycogenosis 2 / Pompe Disease (Infantile-Onset)1
4TerminatedTreatmentPompe's Disease1
Not AvailableApproved for MarketingNot AvailableAcid Maltase Deficiency Disease / Glycogen Storage Disease Type II (GSD-II) / Glycogenosis 2 / Pompe Disease (Late-Onset)1
Not AvailableApproved for MarketingNot AvailableGlycogen Storage Disease Type II / Glycogenosis 21
Not AvailableCompletedTreatmentGlycogen Storage Disease Type II / Glycogenosis 21
Not AvailableNot Yet RecruitingNot AvailableLate Onset Pompe Disease / Pompe's Disease1
Not AvailableRecruitingNot AvailablePompe's Disease2
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous5 mg/mL
Injection, powder, for solutionIntravenous50 mg
Injection, powder, lyophilized, for solutionIntravenous5 mg/mL
Powder, for solutionIntravenous50 mg
Prices
Unit descriptionCostUnit
Myozyme 50 mg vial720.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2416492 No2008-04-292021-07-10Canada
Properties
StateLiquid
Experimental PropertiesNot Available
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

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
binder
General Function:
Transmembrane signaling receptor activity
Specific Function:
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex.
Gene Name:
M6PR
Uniprot ID:
P20645
Molecular Weight:
30993.06 Da
References
  1. Chavez CA, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Dahms NM: Domain 5 of the cation-independent mannose 6-phosphate receptor preferentially binds phosphodiesters (mannose 6-phosphate N-acetylglucosamine ester). Biochemistry. 2007 Nov 6;46(44):12604-17. Epub 2007 Oct 10. [PubMed:17927214 ]
2. Glycogen
Kind
Group
Organism
Human
Pharmacological action
yes
Actions
cleavage
References
  1. Hu D, Kamiya Y, Totani K, Kamiya D, Kawasaki N, Yamaguchi D, Matsuo I, Matsumoto N, Ito Y, Kato K, Yamamoto K: Sugar-binding activity of the MRH domain in the ER alpha-glucosidase II beta subunit is important for efficient glucose trimming. Glycobiology. 2009 Oct;19(10):1127-35. doi: 10.1093/glycob/cwp104. Epub 2009 Jul 22. [PubMed:19625484 ]
  2. Christiansen C, Hachem MA, Glaring MA, Vikso-Nielsen A, Sigurskjold BW, Svensson B, Blennow A: A CBM20 low-affinity starch-binding domain from glucan, water dikinase. FEBS Lett. 2009 Apr 2;583(7):1159-63. doi: 10.1016/j.febslet.2009.02.045. Epub 2009 Mar 9. [PubMed:19275898 ]
Drug created on May 16, 2007 14:19 / Updated on August 17, 2016 12:23