Brands, Medical Use, Clinical Data
- Antineoplastic Agents
- Antiviral Agents
- Immunomodulatory Agents
Brands / Synonyms
Interferon alpha-2 precursor; Interferon alpha-A; LeIF A; PEG-Intron; PEG-Intron (Schering Corp)
PEGylated interferon alpha, total length is 165 amino acids. PEG-Intron is a covalent conjugate of recombinant alfa interferon with monomethoxy polyethylene glycol (PEG). The molecular weight of the PEG portion of the molecule is 12,000 daltons. 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. The average molecular weight of the PEG-Intron molecule is approximately 31,000 daltons. It has a single substitution where K23 is switched to R23
For treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma
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.
Biotrnasformation / Drug Metabolism