==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

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1022 details
Primary information
ThPP IDTh1003
Therapeutic Peptide/Protein NameDornase alfa
SequenceLKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGK view full sequnce in fasta
Functional ClassificationIb
Molecular Weight29253.9
Chemical FormulaC1321H1999N339O396S9
Isoelectric Point4.58
Hydrophobicity-0.083
Melting Point (℃)67
Half LifeN.A.
DescriptionIt is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity.
Indication/DiseaseUsed in the treatment of cystic fibrosis as adjunct therapy.
PharmacodynamicsCystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals.
Mechanism of ActionDornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF.
ToxicityAdverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis,
MetabolismN.A.
AbsorptionSystemic absorption is undetectable when administered via inhalation.
Volume of DistributionN.A.
ClearanceN.A.
CategoriesEnzymes
Patents NumberCA2184581
Date of Issue22/02/05
Date of Expiry28/02/15
Drug InteractionAfrezza (insulin inhalation, rapid acting)
TargetDNA
Information of corresponding available drug in the market
Brand NamePulmozyme
CompanyGenentech Inc
Brand DiscriptionPulmozyme is a synthetic protein that breaks down excess DNA in the pulmonary secretions of people with cystic fibrosis. The protein is produced by genetically engineered CHO cells containing DNA encoding for the native human protein, deoxyribonuclease I.
Prescribed forPulmozyme is used to improve lung function by thinning pulmonary secretions and reducing the risk of respiratory tract infections in people with cystic fibrosis.
Chemical NameN.A.
FormulationThe aqueous formulation contains 1.0 mg/mL dornase alfa, 0.15 mg/mL calcium chloride dihydrate and 8.77 mg/mL sodium chloride. The solution contains no preservative and supports a pH of 6.3.
Physcial AppearnceN.A.
Route of AdministrationAdministered by inhalation of an aerosol mist prod
Recommended DosageN.A.
Contraindicationallergic
Side EffectsSerious side effects include difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives; increased difficulty breathing; chest pain; or fever. Less serious side effects may be voice alteration; sore throat; rash.
Useful Linkhttp://www.patentstorm.us/patents/6348343/fulltext.html
PubMed ID20238314, 19255515, 8792953
3-D StructureTh1003 (View) or (Download)