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10649 details
Primary information
ID10649
Therapeutic IDTh1134
Protein NameAsparaginase erwinia chrysanthemi
Sequence>Th1134_Asparaginase_erwinia_chrysanthemi ADKLPNIVILATGGTIAGSAATGTQTTGYKAGALGVDTLINAVPEVKKLANVKGEQFSNMASENMTGDVVLKLSQRVNELLARDDVDGVVITHGTDTVEESAYFLHLTVKSDKPVVFVAAMRPATAISADGPMNLLEAVRVAGDKQSRGRGVMVVLNDRIGSARYITKTNASTLDTFKANEEGYLGVIIGNRIYYQNRIDKLHTTRSVFDVRGLTSLPKVDILYGYQDDPEYLYDAAIQHGVKGIVYAGMGAGSVSVRGIAGMRKAMEKGVVVIRSTRTGNGIVPPDEELPGLVSDSLNPAHARILLMLALTRTSDPKVIQEYFHTY
Molecular Weight140000
Chemical FormulaC1546H2510N432O476S9
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-life18.2 hours
DescriptionErwinaze (asparaginase from Erwiniachryanthemi) is an asparaginase specific enzyme derived from Erwiniachrysanthemi. L-asparaginase is a homo-tetramer with each subnuit having a molecular weight of about 35 kDa. It is an antineoplastic agent and was FDA approved in November 19, 2011.
Indication/DiseaseAsparaginase Erwinia chryanthemi is for the treatment of patients with acute lymphoblastic leukemia (ALL) that have developed a hypersensitivity to Escherichia coli-derivied asparaginase. It is a component of a multi-agent chemotherpeutic regimen for the treatment of the aforementioned disease and is considered second- or third- line treatment in European and American protocols.
PharmacodynamicsNA
Mechanism of ActionAsparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine in the plasma. The mechanism of action of Erwinaze is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survival.
ToxicityThere are no known cases of overdose with asparaginase _Erwinia chrysanthemi_.[L149] In clinical trials, the most common adverse effects were hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity.[L34714] Pancreatitis occurs in 8-14% of pediatric patients, with adolescents at the highest risk for developing this adverse event. Pancreatitis typically occurs after the first few weeks of asparaginase administration, which suggests this complication occurs from an underlying predisposition rather than a cumulative drug effect.[A7464]
MetabolismMetabolism of asparaginase _Erwinia chrysanthemi_ has not been fully characterized; however, it is suspected to be metabolized into small peptides by catabolic pathways.[L34719]
AbsorptionIn patients two to 80 years of age, intramuscular administration of asparaginase _Erwinia chrysanthemi_ 25,000 International Units (IU)/m2 resulted in serum trough asparaginase concentrations = 0.1 IU/mL at either 48-hour (n=35) or 72-hour (n=13) post third dose. 80% of patients evaluted at 48 hours and 38% of patients evaluated at 72 hours had serum asparaginase activity levels > 0.4 IU/mL.[L149] For asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn, the median tmax is 10 hours and the mean absolute bioavailability is 37% in healthy subjects.[L34719]
The volume of distribution of asparaginase _Erwinia chrysanthemi_ can be up to 5 L/m2.[L1448] The geometric mean (%CV) apparent volume of distribution of asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn was 1.48 L/m2 (49%).[L34719] While asparaginases are not detectable in cerebrospinal fluid, asparagine in cerebrospinal fluid is depleted with systemic administration of any formulation of asparaginases.[L1448]
ClearanceThe geometric mean (%CV) apparent clearance of asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn is 0.31 L/hour/m2 (36%).[L34719]
CategoriesAmidohydrolases,Antineoplastic Agents,Asparaginase,Asparagine-specific Enzyme,Enzymes,Enzymes and Coenzymes,Hepatotoxic Agents,Hydrolases,Narrow Therapeutic Index Drugs,Thyroxine-binding globulin inhibitors
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetNA
Brand NameErwinaze
CompanyEUSA Pharma
Brand DescriptionEUSA Pharma
Prescribed Foracute lymphoblastic leukemia
Chemical NameNA
FormulationEach vial contains 10,000 International Units of asparaginase Erwinia chrysanthemi, and the following inactive ingredients: glucose monohydrate (5.0 mg), sodium chloride (0.5 mg).
Physical Appearance ERWINAZE is supplied as a Sterile, lyophilized, white powder in vials.
Route of AdministrationIntramuscular
Recommended Dosage25,000 International Units/m²
ContraindicationHypersensitivity reactions to ERWINAZE, including anaphylaxis., pancreatitis with prior L-asparaginase therapy, thrombosis with prior L-asparaginase therapy, hemorrhagic events with prior L-asparaginase therapy.
Side EffectsHypersensitivity reactions, Pancreatitis, Glucose intolerance, Thrombosis and hemorrhage
Useful Link 1Link
Useful Link 2NA
RemarksNA