| Primary information |
|---|
| ThPP ID | Th1086 |
| Therapeutic Peptide/Protein Name | Interferon alfa-2b |
| Sequence | CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKA view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 19271 |
| Chemical Formula | C860H1353N229O255S9 |
| Isoelectric Point | 5.99 |
| Hydrophobicity | -0.339 |
| Melting Point (℃) | 61 |
| Half Life | The elimination half-life following both intramuscular and subcutaneous injections was approximately |
| Description | Recombinant type-I Interferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced), composed of 165 amino acid residues with R at position 23. It resembles leukocyte secreted interferon. Widely used as an antiviral or antineoplastic agent. |
| Indication/Disease | For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma. |
| 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 | 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 | There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally. |
| Metabolism | N.A. |
| Absorption | Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Immunosuppressive Agents |
| Patents Number | CA1341567 |
| Date of Issue | 20/02/12 |
| Date of Expiry | 20/02/29 |
| Drug Interaction | N.A. |
| Target | Granulocyte colony-stimulating factor receptor,Neutrophil elastase |
| Information of corresponding available drug in the market |
|---|
| Brand Name | INTRON A |
| Company | Merck |
| Brand Discription | INTRON A recombinant for Injection has been classified as an alpha interferon and 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 alfa2b gene from human leukocytes. The fermentation is carried out in a defined nutrient medium containing the antibiotic tetracycline hydrochloride at a concentration of 5 to 10 mg/L; the presence of this antibiotic is not detectable in the final product. The specific activity of interferon alfa-2b, recombinant is approximately 2.6 x 108 IU/mg protein as measured by the HPLC assay. |
| Prescribed for | Hairy Cell Leukemia, Malignant Melanoma, Follicular Lymphoma, Condylomata Acuminata, AIDS-Related Kaposi's Sarcoma, Chronic Hepatitis C, Chronic Hepatitis B, |
| Chemical Name | N.A. |
| Formulation | INTRON A Powder for Injection, 10 million IU per vial and Diluent for INTRON A (Sterile Water for Injection USP) 1 mL per vial, INTRON A Solution for Injection, 18 million IU multidose vial (22.8 million IU per 3.8 mL per vial); boxes containing 1 vial of INTRON A Solution for Injection |
| Physcial Appearnce | Powder or solution |
| Route of Administration | IntramuSubcutaneousular, Subcutaneous, Intralesion |
| Recommended Dosage | Not all dosage forms and strengths are appropriate for some indications. To enhance the tolerability of INTRON A, injections should be administered in the evening when possible; To reduce the incidence of certain adverse reactions, acetaminophen may be administered at the time of injection;The solution should be allowed to come to room temperature before using. |
| Contraindication | Alpha interferons, including INTRON A, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping INTRON A therapy. |
| Side Effects | most frequently reported adverse reactions were “flu-like†symptoms, particularly fever, headache, chills, myalgia, and fatigue. More severe toxicities are observed generally at higher doses and may be difficult for patients to tolerate. |
| Useful Link | hthttp://www.drugs.com/drp/interferon-alfa-2b-recombinant.html tp://www.rxlist.com/intron-a-drug.htm |
| PubMed ID | 12691141, 12560429, 10532768, 9972624 |
| 3-D Structure | Th1086 (View) or (Download) |