Pegademase

Identification

Summary

Pegademase is a modified form of bovine adenosine deaminase used to treat adenosine deaminase deficiency, a condition which leads to the formation of adenosine metabolites which are cytotoxic to lymphocytes.

Generic Name
Pegademase
DrugBank Accession Number
DB00061
Background

Bovine adenosine deaminase derived from bovine intestine that has been extensively pegylated for extended serum half life.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Structure
Db00061
Protein Chemical Formula
C1821H2834N484O552S14
Protein Average Weight
40788.2 Da
Sequences
>DB00061 sequence
MAQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPE
FLAKFDYYMPAIAGCREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAI
DLAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGY
HTLEDATLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIF
KSTLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPASAE
QCL
Download FASTA Format
Synonyms
  • (monomethoxypolyethylene glycol succinimidyl) 11-17-adenosine deaminase
  • PEG-adenosine deaminase
  • pegADA
  • Pegademase
  • Pegademase bovine

Pharmacology

Indication

For treatment of adenosine deaminase deficiency

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Used to replace deficient or inactive adenosine deaminase which leads to severe combined immunodeficiency disease (SCID). The enzyme is responsible for converting adenosine to inosine. In the absence of adenosine deaminase, the purine substrates adenosine, 2'-deoxyadenosine and their metabolites are actually toxic to lymphocytes thereby leading to diminished immune function.

Mechanism of action

Pegademase converts adenosine (toxic) to inosine (less toxic) by deamination. It also converts 2'-deoxyadenosine to 2'-deoxyinosine via deamination.

TargetActionsOrganism
AAdenosine
metabolizer
Humans
UGrowth factor receptor-bound protein 2
binder
Humans
Absorption

Time to peak for plasma adenosine deaminase is 2 to 3 days

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

plasma adenosine deaminase elimination half-life is 3 to >6 days

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

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.
DrugInteraction
Antihemophilic factor (recombinant), PEGylatedThe therapeutic efficacy of Antihemophilic factor (recombinant), PEGylated can be decreased when used in combination with Pegademase.
Certolizumab pegolThe therapeutic efficacy of Certolizumab pegol can be decreased when used in combination with Pegademase.
Damoctocog alfa pegolThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Pegademase.
ElapegademaseThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegademase.
LipegfilgrastimThe therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Pegademase.
Methoxy polyethylene glycol-epoetin betaThe therapeutic efficacy of Methoxy polyethylene glycol-epoetin beta can be decreased when used in combination with Pegademase.
Nonacog beta pegolThe therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Pegademase.
PegaptanibThe therapeutic efficacy of Pegaptanib can be decreased when used in combination with Pegademase.
PegaspargaseThe therapeutic efficacy of Pegademase can be decreased when used in combination with Pegaspargase.
PegfilgrastimThe therapeutic efficacy of Pegademase can be decreased when used in combination with Pegfilgrastim.
Interactions
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdagenInjection, solution250 [iU]/1mLIntramuscularLeadiant Biosciences, Inc.2010-10-182019-06-30US flag

Categories

ATC Codes
L03AX04 — Pegademase
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
HW3H7D91F6
CAS number
130167-68-9

References

Synthesis Reference

Paul Skonezny, "Process for preparing dideoxyinosine using adenosine deaminase enzyme." U.S. Patent US20040175804, issued September 09, 2004.

US20040175804
General References
Not Available
UniProt
P56658
Genbank
AF280603
PubChem Substance
46508490
RxNav
59768
ChEMBL
CHEMBL1201514
PharmGKB
PA450831
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Adenosine_deaminase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentADA-SCID / Adenosine Deaminase Deficiency / Severe Combined Immunodeficiency1

Pharmacoeconomics

Manufacturers
  • Sigma tau pharmaceuticals inc
Packagers
  • Ben Venue Laboratories Inc.
  • Enzon Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntramuscular250 [iU]/1mL
Prices
Unit descriptionCostUnit
Adagen 250 unit/ml vial4375.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.428Not Available
isoelectric point5.33Not Available

Targets

Drugtargets
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Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
Actions
Metabolizer
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. 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]
  3. Van Linden A, Eltzschig HK: Role of pulmonary adenosine during hypoxia: extracellular generation, signaling and metabolism by surface adenosine deaminase/CD26. Expert Opin Biol Ther. 2007 Sep;7(9):1437-47. [Article]
  4. Kemeny-Beke A, Jakab A, Zsuga J, Vecsernyes M, Karsai D, Pasztor F, Grenczer M, Szentmiklosi AJ, Berta A, Gesztelyi R: Adenosine deaminase inhibition enhances the inotropic response mediated by A1 adenosine receptor in hyperthyroid guinea pig atrium. Pharmacol Res. 2007 Aug;56(2):124-31. Epub 2007 May 10. [Article]
  5. Mohsenin A, Mi T, Xia Y, Kellems RE, Chen JF, Blackburn MR: Genetic removal of the A2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L753-61. Epub 2007 Jun 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Sh3/sh2 adaptor activity
Specific Function
Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (...
Gene Name
GRB2
Uniprot ID
P62993
Uniprot Name
Growth factor receptor-bound protein 2
Molecular Weight
25206.21 Da
References
  1. Ramos-Morales F, Dominguez A, Rios RM, Barroso SI, Infante C, Schweighoffer F, Tocque B, Pintor-Toro JA, Tortolero M: Adenosine deaminase is a specific partner for the Grb2 isoform Grb3-3. Biochem Biophys Res Commun. 1997 Aug 28;237(3):735-40. [Article]

Drug created on June 13, 2005 13:24 / Updated on April 03, 2021 09:33