Pegaspargase
Identification
- Name
- Pegaspargase
- Accession Number
- DB00059 (BTD00079, BIOD00079)
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Description
Pegylated L-asparagine amidohydrolase from E. coli. Pegylation substantially (by a factor of 4) extends the protein half life.
- Protein structure
- Protein chemical formula
- C1377H2208N382O442S17
- Protein average weight
- 31731.9 Da
- Sequences
>DB00059 sequence MEFFKKTALAALVMGFSGAALALPNITILATGGTIAGGGDSATKSNYTVGKVGVENLVNA VPQLKDIANVKGEQVVNIGSQDMNDNVWLTLAKKINTDCDKTDGFVITHGTDTMEETAYF LDLTVKCDKPVVMVGAMRPSTSMSADGPFNLYNAVVTAADKASANRGVLVVMNDTVLDGR DVTKTNTTDVATFKSVNYGPLGYIHNGKIDYQRTPARKHTSDTPFDVSKLNELPKVGIVY NYANASDLPAKALVDAGYDGIVSAGVGNGNLYKSVFDTLATAAKTGTAVVRSSRVPTGAT TQDAEVDDAKYGFVASGTLNPQKARVLLQLALTQTKDPQQIQQIFNQY
Download FASTA Format- Synonyms
- Peg-asparaginase
- Peg/L-asparaginase
- Pegaspargasa
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Oncaspar Injection, solution 750 [iU]/1mL Intramuscular; Intravenous Sigma Tau Pharmaceuticals, Inc. 1994-02-01 2016-11-30 US 
Oncaspar Solution 750 unit Intramuscular; Intravenous Shire Pharma Canada Ulc 2017-06-01 Not applicable Canada 
Oncaspar Injection, solution 750 U/ml Baxalta Innovations Gmb H 2016-01-14 Not applicable EU 
Oncaspar Injection, solution 750 [iU]/1mL Intramuscular; Intravenous Baxalta US Inc. 1994-02-01 Not applicable US Oncaspar Liquid 750 unit Intramuscular; Intravenous Aventis Pharma Ltd. 1998-10-13 Not applicable Canada - Categories
- Alcohols
- Amidohydrolases
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Asparaginase
- Asparagine-specific Enzyme
- Biomedical and Dental Materials
- Delayed-Action Preparations
- Enzymes
- Enzymes and Coenzymes
- Enzymes, Immobilized
- Ethylene Glycols
- Glycols
- Hydrolases
- Immunosuppressive Agents
- Macromolecular Substances
- Pegylated agents
- Polymers
- UNII
- 7D96IR0PPM
- CAS number
- 130167-69-0
Pharmacology
- Indication
For treatment of acute lymphoblastic leukemia
- Associated Conditions
- Pharmacodynamics
In a significant number of patients with acute leukemia, the malignant cells are dependent on an exogenous source of asparagine for survival. Normal cells, however, are able to synthesize asparagine and thus are affected less by the rapid depletion produced by treatment with the enzyme asparaginase. Oncaspar exploits a metabolic defect in asparagine synthesis of some malignant cells.
- Mechanism of action
Pegaspargase, more effective than asparaginase, converts asparagine to aspartic acid and ammonia. It facilitates production of oxaloacetate which is needed for general cellular metabolism. Some malignant cells lose the ability to produce asparagine and so the loss of exogenous sources of asparagine leads to cell death.
Target Actions Organism AL-asparagine other/unknownHumans - Absorption
Onset of Asparagine depletion by IM is within 4 days Time to peak: IM: 3 to 4 days
- Volume of distribution
IV: Adults (asparaginase naive): 2.4 L/m2 Distributes into CSF (reportedly reducing CSF asparagine concentrations to a similar extent as asparaginase
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half life
IM: ~6 days; half-life decreased to ~3 days (range: 1.4 to 5 days) in patients with previous hypersensitivity to native L-asparaginase; IV: Adults (asparaginase naive): 7 days
- Clearance
- Not Available
- Toxicity
Adverse effects that occur more than 10% of the time include hepatotoxicity as it is known to increase serum transaminases (ALT, AST). Also known to induce hypersensitivity reactions including anaphylaxis, erythema and bronchospasm.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 2-Methoxyethanol The risk or severity of adverse effects can be increased when Pegaspargase is combined with 2-Methoxyethanol. 9-(N-methyl-L-isoleucine)-cyclosporin A The risk or severity of adverse effects can be increased when Pegaspargase is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A. Abatacept The risk or severity of adverse effects can be increased when Pegaspargase is combined with Abatacept. Abetimus The risk or severity of adverse effects can be increased when Pegaspargase is combined with Abetimus. Abicipar Pegol The therapeutic efficacy of Abicipar Pegol can be decreased when used in combination with Pegaspargase. Acteoside The risk or severity of adverse effects can be increased when Pegaspargase is combined with Acteoside. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Pegaspargase. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pegaspargase. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Pegaspargase. Afelimomab The risk or severity of adverse effects can be increased when Pegaspargase is combined with Afelimomab. - Food Interactions
- Not Available
References
- General References
- Graham ML: Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev. 2003 Sep 26;55(10):1293-302. [PubMed:14499708]
- Link [Link]
- External Links
- UniProt
- P37595
- Genbank
- U00096
- PubChem Substance
- 46505366
- ChEMBL
- CHEMBL2108546
- PharmGKB
- PA164760860
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pegaspargase
- ATC Codes
- L01XX24 — Pegaspargase
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- FDA label
- Download (400 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Ben Venue Laboratories Inc.
- Enzon Inc.
- Dosage forms
Form Route Strength Injection, solution 750 U/ml Injection, solution Intramuscular; Intravenous 750 [iU]/1mL Liquid Intramuscular; Intravenous 750 unit Solution Intramuscular; Intravenous 750 unit - Prices
Unit description Cost Unit Oncaspar 750 unit/ml vial 656.0USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source hydrophobicity 0.059 Not Available isoelectric point 4.67 Not Available
Taxonomy
- 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
Targets
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- 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. [PubMed:17016423]
- Douer D, Yampolsky H, Cohen LJ, Watkins K, Levine AM, Periclou AP, Avramis VI: Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia. Blood. 2007 Apr 1;109(7):2744-50. [PubMed:17132721]
- Wetzler M, Sanford BL, Kurtzberg J, DeOliveira D, Frankel SR, Powell BL, Kolitz JE, Bloomfield CD, Larson RA: Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood. 2007 May 15;109(10):4164-7. Epub 2007 Jan 30. [PubMed:17264295]
- Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R: FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007 Aug;12(8):991-8. [PubMed:17766659]
Drug created on June 13, 2005 07:24 / Updated on January 22, 2019 20:52