A database of FDA approved therapeutic peptides and proteins
| This page displays user query in tabular form. |
1022 details |
| Primary information | |
|---|---|
| ThPP ID | Th1003 |
| Therapeutic Peptide/Protein Name | Dornase alfa |
| Sequence | LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGK view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 29253.9 |
| Chemical Formula | C1321H1999N339O396S9 |
| Isoelectric Point | 4.58 |
| Hydrophobicity | -0.083 |
| Melting Point (℃) | 67 |
| Half Life | N.A. |
| Description | It 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/Disease | Used in the treatment of cystic fibrosis as adjunct therapy. |
| Pharmacodynamics | Cystic 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 Action | Dornase 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. |
| Toxicity | Adverse 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, |
| Metabolism | N.A. |
| Absorption | Systemic absorption is undetectable when administered via inhalation. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Enzymes |
| Patents Number | CA2184581 |
| Date of Issue | 22/02/05 |
| Date of Expiry | 28/02/15 |
| Drug Interaction | Afrezza (insulin inhalation, rapid acting) |
| Target | DNA |
| Information of corresponding available drug in the market | |
| Brand Name | Pulmozyme |
| Company | Genentech Inc |
| Brand Discription | Pulmozyme 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 for | Pulmozyme is used to improve lung function by thinning pulmonary secretions and reducing the risk of respiratory tract infections in people with cystic fibrosis. |
| Chemical Name | N.A. |
| Formulation | The 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 Appearnce | N.A. |
| Route of Administration | Administered by inhalation of an aerosol mist prod |
| Recommended Dosage | N.A. |
| Contraindication | allergic |
| Side Effects | Serious 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 Link | http://www.patentstorm.us/patents/6348343/fulltext.html |
| PubMed ID | 20238314, 19255515, 8792953 |
| 3-D Structure | Th1003 (View) or (Download) |