| Primary information |
|---|
| ThPP ID | Th1008 |
| Therapeutic Peptide/Protein Name | Peginterferon alfa-2a |
| Sequence | CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 60000 |
| Chemical Formula | N.A. |
| Isoelectric Point | 5.99 |
| Hydrophobicity | N.A. |
| Melting Point (℃) | 61 |
| Half Life | Terminal half life is 80 hours (range 50 to 140 hours). |
| Description | Human interferon 2a, is a covalent conjugate of recombinant interferon alfa-2a with a single branched bis-mono-methoxy polyethylene glycol (PEG) chain. The PEG moiety is linked at a single site to the interferon alfa moiety via a stable amide bond to lysine. Peginterferon alfa-2a has an approximate molecular weight of 60,000 daltons. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted and expressed in Escherichia coli. The resultant protein is 165 amino acids. 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 | To treat hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma. |
| Pharmacodynamics | Upregulates the expression of MHC I proteins which increases presentation of peptides derived from viral antigens. Thus enhancing the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and make 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 | Interferon alpha 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 | N.A. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Immunosuppressive Agents |
| Patents Number | CA2203480 |
| Date of Issue | 30/06/09 |
| Date of Expiry | 23/04/17 |
| Drug Interaction | Interferon increases the effect and toxicity of theophylline called Aminophylline |
| Target | Interferon alpha/beta receptor 1,Interferon alpha/beta receptor 2 |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Pegasys |
| Company | Hoffman-La Roche Inc |
| Brand Discription | PEGASYS is a covalent conjugate of recombinant alfa-2a interferon (approximate molecular weight [MW] 20,000 daltons) with a single branched bis-mono-methoxy polyethylene glycol (PEG) chain (approximate MW 40,000 daltons). The PEG moiety is linked at a sin |
| Prescribed for | Pegasys is used to treat chronic hepatitis B or C (adults), and to treat chronic hepatitis C (children 5 or more years of age). It is mostly used with ribavirin |
| Chemical Name | N.A. |
| Formulation | Each vial of 180 mcg/mL peginterferon alfa-2a (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.05 mg), benzyl alcohol (10 mg), polysorbate 80 (0.05 mg), sodium acetate trihydrate (2.62 mg), and sodium chloride (8 mg) at pH 6 ± |
| Physcial Appearnce | Sterile, preservative-free, colorless to light yellow injectable solution |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | Pegasys is usually given once a week. |
| Contraindication | Allergic |
| Side Effects | Nausea, vomiting, loss of appetite; headache, muscle pain, feeling weak or tired; sleep problems (insomnia); temporary hair loss; or itching, redness, dryness, or swelling where the medicine was injected. |
| Useful Link | http://www.pegasys.com/ |
| PubMed ID | 28210927, 27495085, 27183377, 27062488, 27049487, 26222859, 26202757, 26188762, 25801095 |
| 3-D Structure | Th1008 (View) or (Download) |