Identification

Name
Asparaginase
Accession Number
DB00023  (BTD00011, BIOD00011)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

L-asparagine amidohydrolase from E. coli

Protein structure
Db00023
Protein chemical formula
C1377H2208N382O442S17
Protein average weight
31731.9 Da
Sequences
> Elspar Sequence
QMSLQQELRYIEALSAIVETGQKMLEAGESALDVVTEAVRLLEECPLFNAGIGAVFTRDE
THELDACVMDGNTLKAGAVAGVSHLRNPVLAARLVMEQSPHVMMIGEGAENFAFARGMER
VSPEIFSTSLRYEQLLAARKEGATVLDHSGAPLDEKQKMGTVGAVALDLDGNLAAATSTG
GMTNKLPGRVGDSPLVGAGCYANNASVAVSCTGTGEVFIRALAAYDIAALMDYGGLSLAE
ACERVVMEKLPTLGGSGGLIAIDHEGNVALPFNTEGMYRAWGYAGDTPTTGIYREKGDTV
ATQ
>sp|P00805|ASPG2_ECOLI L-asparaginase 2 OS=Escherichia coli (strain K12) GN=ansB PE=1 SV=2
MEFFKKTALAALVMGFSGAALALPNITILATGGTIAGGGDSATKSNYTVGKVGVENLVNA
VPQLKDIANVKGEQVVNIGSQDMNDNVWLTLAKKINTDCDKTDGFVITHGTDTMEETAYF
LDLTVKCDKPVVMVGAMRPSTSMSADGPFNLYNAVVTAADKASANRGVLVVMNDTVLDGR
DVTKTNTTDVATFKSVNYGPLGYIHNGKIDYQRTPARKHTSDTPFDVSKLNELPKVGIVY
NYANASDLPAKALVDAGYDGIVSAGVGNGNLYKSVFDTLATAAKTGTAVVRSSRVPTGAT
TQDAEVDDAKYGFVASGTLNPQKARVLLQLALTQTKDPQQIQQIFNQY
Download FASTA Format
Synonyms
  • Asparaginase (E. coli)
  • Escherichia coli L-asparaginase
  • L-asparaginase
  • L-asparagine amidohydrolase
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ErwinasePowder, for solution10000 unitIntramuscular; Intravenous; SubcutaneousJazz Pharmaceuticals France Sas2009-07-01Not applicableCanada
KidrolasePowder, for solution10000 unitIntramuscular; IntravenousJazz Pharmaceuticals France Sas1974-12-31Not applicableCanada
SpectrilaInjection, powder, for solution10000 UIntravenousMedac Gesellschaft Fuer Klinische Spezialpraeparate Mb H2016-01-14Not applicableEu
SpectrilaInjection, powder, for solution10000 UIntravenousMedac Gesellschaft Fuer Klinische Spezialpraeparate Mb H2016-01-14Not applicableEu
International/Other Brands
Elspar (Merck & Co. Inc)
Categories
UNII
G4FQ3CKY5R
CAS number
9015-68-3

Pharmacology

Indication

For treatment of acute lympocytic leukemia and non-Hodgkins lymphoma

Structured Indications
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. Elspar exploits a metabolic defect in asparagine synthesis of some malignant cells.

Mechanism of action

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.

TargetActionsOrganism
AL-asparagine
other/unknown
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

8-30 hrs

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Asparaginase.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Asparaginase.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Asparaginase.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Asparaginase.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Asparaginase.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Asparaginase.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Asparaginase.Approved
DexamethasoneThe serum concentration of Dexamethasone can be increased when it is combined with Asparaginase.Approved, Investigational, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Asparaginase.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Asparaginase.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Asparaginase.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Asparaginase.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Asparaginase.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Asparaginase.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Asparaginase.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Asparaginase.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Asparaginase.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Asparaginase.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Asparaginase.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Asparaginase.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Asparaginase.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Masao Nambu, "Process for producing immobilized L-asparaginase preparations for the therapy of leukemia." U.S. Patent US4617271, issued January, 1977.

US4617271
General References
  1. Appel IM, van Kessel-Bakvis C, Stigter R, Pieters R: Influence of two different regimens of concomitant treatment with asparaginase and dexamethasone on hemostasis in childhood acute lymphoblastic leukemia. Leukemia. 2007 Nov;21(11):2377-80. Epub 2007 Jun 7. [PubMed:17554375]
  2. Link [Link]
External Links
UniProt
P37595
Genbank
U00096
PubChem Substance
46507633
ChEMBL
CHEMBL2108989
PharmGKB
PA448492
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Asparaginase
ATC Codes
L01XX02 — Asparaginase
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (880 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherLeukemia Acute Myeloid Leukemia (AML)1
1CompletedSupportive CareAcute Lymphoblastic Leukaemias (ALL) / Non Hodgkins Lymphoma1
1CompletedTreatmentAcute Lymphoid Leukemia Relapse / Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant1
1CompletedTreatmentLeukemias1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1TerminatedTreatmentAcute Lymphoblastic Leukaemia Recurrent / Allergy to Native e.Coli Asparaginase / Allergy to PEG e.Coli Asparaginase1
1, 2Active Not RecruitingTreatmentRecurrent Childhood Acute Lymphoblastic Leukemia1
1, 2CompletedTreatmentAcute Undifferentiated Leukemia (AUL) / B-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / L1 Adult Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Adult Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / T-cell Adult Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL)1
2CompletedTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Lymphoblastic Lymphoma / T-cell Adult Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia1
2CompletedTreatmentLeukemias10
2CompletedTreatmentLeukemias / Malignant Lymphomas2
2CompletedTreatmentLeukemias / Neutropenias / Thrombocytopenias1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentAcute B-Cell Lymphoblastic Leukaemia1
2Not Yet RecruitingTreatmentB Acute Lymphoblastic Leukemia / B Lymphoblastic Lymphoma / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent B Lymphoblastic Lymphoma / Recurrent T Lymphoblastic Leukemia/Lymphoma / Refractory B Lymphoblastic Lymphoma / Refractory T Lymphoblastic Lymphoma / T Acute Lymphoblastic Leukemia / T Lymphoblastic Lymphoma1
2Not Yet RecruitingTreatmentMalignancies, Hematologic1
2RecruitingTreatmentExtranodal NK-T-CELL LYMPHOMA / NK/T Cell Lymphoma1
2RecruitingTreatmentLymphoma, Extranodal NK-T-Cell1
2TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Mixed Lineage Acute Leukemia1
2TerminatedTreatmentLymphoma, Lymphoblastic1
2TerminatedTreatmentRecurrent Adult Acute Lymphoblastic Leukemia1
2Unknown StatusTreatmentLeukemias2
2Unknown StatusTreatmentLymphoblastic Leukemia, Acute1
2WithdrawnTreatmentAcute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)1
2, 3CompletedTreatmentAcute Lymphoblastic Leukemia, in Relapse1
2, 3CompletedTreatmentAdult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
2, 3Unknown StatusTreatmentLeukemias1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAcute Undifferentiated Leukemia (AUL) / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Intermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentChildhood Acute Basophilic Leukemia / Childhood Acute Eosinophilic Leukemia / Childhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / De Novo Myelodysplastic Syndromes / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3Active Not RecruitingTreatmentDrug/Agent Toxicity by Tissue/Organ / Leukemias1
3Active Not RecruitingTreatmentGranulocytic Sarcoma / Leukaemia cutis / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Myeloid Neoplasm1
3Active Not RecruitingTreatmentLeukemias1
3Active Not RecruitingTreatmentMalignant Lymphomas1
3CompletedSupportive CareCardiac Toxicity / Leukemias / Malignant Lymphomas1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)2
3CompletedTreatmentChildhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Refractory Anemia With Ringed Sideroblasts / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentChildhood Acute Lymphoblastic Leukemia in Remission / Recurrent Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentLeukemias9
3CompletedTreatmentLeukemias / Malignant Lymphomas1
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentChildhood Acute Myeloid Leukemia / Childhood Myelodysplastic Syndrome / Cytopenias / Down Syndrome (DS) / Myeloid Leukemia Associated With Down Syndrome / Myeloproliferative Neoplasms1
3TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3TerminatedTreatmentMalignant Lymphomas1
3Unknown StatusTreatmentLeukemias2
3Unknown StatusTreatmentLeukemias / Malignant Lymphomas1
3Unknown StatusTreatmentLymphoblastic Leukemia, Acute1
3Unknown StatusTreatmentMalignant Lymphomas2
3WithdrawnTreatmentLeukemias1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)5
4CompletedTreatmentAdult Acute Lymphocytic Leukemia3
4CompletedTreatmentLymphoma, Lymphoblastic1
4RecruitingTreatmentAcute Lymphobkastic Leukemia1
4RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL)1
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia2
Not AvailableActive Not RecruitingTreatmentAdult Acute Lymphoblastic Leukemia / Childhood Acute Lymphoblastic Leukemia1
Not AvailableActive Not RecruitingTreatmentLeukemias1
Not AvailableCompletedTreatmentL1 Childhood Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / Non-T, Non-B Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia1
Not AvailableCompletedTreatmentLeukemia, Lymphocytic, Acute1
Not AvailableCompletedTreatmentLeukemias1
Not AvailableCompletedTreatmentLymphoma, Lymphoblastic1
Not AvailableCompletedTreatmentT-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableNo Longer AvailableNot AvailableAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphocytic Leukemia (ALL)1
Not AvailableUnknown StatusTreatmentLeukemias2
Not AvailableUnknown StatusTreatmentPh-negative Adult Acute Lymphoblastic Leukemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular; Intravenous; Subcutaneous10000 unit
Powder, for solutionIntramuscular; Intravenous10000 unit
Injection, powder, for solutionIntravenous10000 U
Prices
Unit descriptionCostUnit
Elspar 10000 unit vial74.6USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity0.059Not Available
isoelectric point4.67Not 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

1. L-asparagine
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. 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]
  4. Wenner KA, Vieira Pinheiro JP, Escherich G, Wessalowski R, Jorch N, Wolff J, Stehn M, Kohlschutter A, Boos J, Janka-Schaub GE: Asparagine concentration in plasma after 2,500 IU/m(2) PEG-asparaginase i.v. in children with acute lymphoblastic leukemia. Klin Padiatr. 2005 Nov-Dec;217(6):321-6. [PubMed:16307417]
  5. Appel IM, Pinheiro JP, den Boer ML, Lanvers C, Reniers NC, Boos J, Pieters R: Lack of asparagine depletion in the cerebrospinal fluid after one intravenous dose of PEG-asparaginase: a window study at initial diagnosis of childhood ALL. Leukemia. 2003 Nov;17(11):2254-6. [PubMed:14523472]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33