DB00069 - Interferon alfacon-1
| Identification | |
|---|---|
| Name | Interferon alfacon-1 |
| Accession Number | DB00069 (BIOD00062, BTD00062) |
| Type | biotech |
| Description | Interferon alfacon-1 is a recombinant non-naturally occurring type-I interferon. The 166-amino acid sequence of Interferon alfacon-1 was derived by scanning the sequences of several natural interferon alpha subtypes and assigning the most frequently observed amino acid in each corresponding position. Four additional amino acid changes were made to facilitate the molecular construction, and a corresponding synthetic DNA sequence was constructed using chemical synthesis methodology. Interferon alfacon-1 differs from interferon alfa-2b at 20/166 amino acids (88% homology), and comparison with interferon-beta shows identity at over 30% of the amino acid positions. Interferon alfacon-1 is produced in Escherichia coli (E. coli) cells that have been genetically altered by insertion of a synthetically constructed sequence that codes for Interferon alfacon-1. Prior to final purification, Interferon alfacon-1 is allowed to oxidize to its native state, and its final purity is achieved by sequential passage over a series of chromatography columns. This protein has a molecular weight of 19,434 daltons. |
| Structure |
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| Categories (*) | |
| Molecular Weight | 19343.0000 |
| Groups | approved |
| Monoisotopic Weight | Not Available |
| Pharmacology | |
| Indication | For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma |
| 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. |
| Absorption | Subcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys. |
| Protein binding | Not Available |
| Biotransformation | Not Available |
| Route of elimination | Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys, was due predominantly to catabolism and excretion by the kidneys. |
| Toxicity | Reproductive toxicity studies in pregnant rhesus monkeys and golden Syrian hamsters demonstrated an increase in fetal loss in hamsters treated with Interferon alfacon-1 at doses of > 150 mcg/kg/day, and in rhesus monkeys at doses of 3 and 10 mcg/kg/day. The Interferon alfacon-1 toxicity profile described is consistent with the known toxicity profile of other alpha interferons. |
| Affected organisms |
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| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions | Not Available |
Targets
| Interferon-alpha/beta receptor alpha chain | |
|---|---|
| Name | Interferon-alpha/beta receptor alpha chain |
| Gene Name | IFNAR1 |
| Pharmacological action | yes |
| Actions | binder |
| References |
|
| DTHybrid score | 1.8511 |
| Interferon-alpha/beta receptor beta chain | |
| Name | Interferon-alpha/beta receptor beta chain |
| Gene Name | IFNAR2 |
| Pharmacological action | yes |
| Actions | binder |
| References |
|
| DTHybrid score | 1.8511 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|