| Primary information |
|---|
| ThPP ID | Th1019 |
| Therapeutic Peptide/Protein Name | Peginterferon alfa-2b |
| Sequence | CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 31000 |
| Chemical Formula | C130H219N43O42 |
| Isoelectric Point | 5.99 |
| Hydrophobicity | N.A. |
| Melting Point (℃) | 61 |
| Half Life | Approximately 40 hours (range 22 to 60 hours) in patients with HCV infection |
| Description | Peginterferon alfa-2b is a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol (PEG). The average molecular weight of the PEG portion of the molecule is 12,000 daltons. The average molecular weight of the PEG-Intron molecule is approximately 31,000 daltons. The specific activity of peginterferon alfa-2b is approximately 0.7 x 108 IU/mg protein. Interferon alfa-2b is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon gene from human leukocytes. The PEG strand protects the molecule in vivo from proteolytic breakdown, substantially increases its in vivo half-life, and reduces immunogenicity by wrapping around and physically hindering access to the protein portion of the molecule. |
| Indication/Disease | Used for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha who have compensated liver disease and are at least 18 years of age. |
| Pharmacodynamics | Upregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2-5 oligoadenylate synthetase (2-5 A synthetase) and protein kinase R. |
| Mechanism of Action | It binds to type I interferon receptors IFNAR1 and IFNAR2c which upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription)which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta. |
| Toxicity | N.A. |
| Metabolism | N.A. |
| Absorption | After a single subcutaneous dose of peginterferon alfa-2b, the mean absorption half-life was 4.6 hours. |
| Volume of Distribution | N.A. |
| Clearance | Oral cl=22 mL/hr/kg [patients with HCV infection], Renal elimination accounts for 30% of the clearance. |
| Categories | Immunosuppressive Agents |
| Patents Number | CA2329474 |
| Date of Issue | 0002-02-26 |
| Date of Expiry | 31/10/16 |
| Drug Interaction | Dyphylline.Interferon increases the effect and toxicity of theophylline |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | N.A. |
| Company | N.A. |
| Brand Discription | N.A. |
| Prescribed for | N.A. |
| Chemical Name | N.A. |
| Formulation | N.A. |
| Physcial Appearnce | N.A. |
| Route of Administration | N.A. |
| Recommended Dosage | N.A. |
| Contraindication | N.A. |
| Side Effects | Headache, joint or muscle pain; nausea, dry mouth, loss of appetite, weight loss; dizziness, sleep problems (insomnia), feeling mildly anxious, depressed, or irritable; or pain, redness, swelling, or irritation where the medicine was injected. |
| Useful Link | http://www.rxlist.com/peg-intron-drug.htm |
| PubMed ID | 26280154, 26261238, 25771464, 25117425, 25068004, 24974131, 24119723, 24059964, 23746377 |
| 3-D Structure | Th1019 (View) or (Download) |