Peginterferon alfa-2b

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Peginterferon alfa-2b
Systematic (IUPAC) name
PEGylated human interferon alpha 2b
Clinical data
AHFS/ Consumer Drug Information
MedlinePlus a605030
  • contraindicated[1]
Pharmacokinetic data
Biological half-life 22–60 hrs
CAS Number 99210-65-8 YesY
ATC code L03AB10 (WHO)
DrugBank DB00022 YesY
ChemSpider none
KEGG D02745 YesY
Chemical data
Formula C860H1353N229O255S9
Molar mass 19269.1 g/mol
 NYesY (what is this?)  (verify)

Pegylated interferon alfa-2b is a treatment for hepatitis C developed by Schering-Plough, brand name is PegIntron.

It was approved in January 2001.

It has also been approved as treatment for melanoma with nodal involvement after surgical resection, under the brand name Sylatron by Merck in April 2011.

PEG-interferon alpha is a pegylated interferon composed of 165 amino acids. The PEG (polyethylene glycol) protects the molecule from proteolytic breakdown and increases the biological half-life of the interferon protein.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]

Mechanism of action[edit]

One of the major mechanisms of PEG-interferon alpha-2b utilizes the JAK-STAT signaling pathway. The basic mechanism works such that PEG-interferon alpha-2b will bind to its receptor, interferon-alpha receptor 1 and 2 (IFNAR1/2). Upon ligand binding the Tyk2 protein associated with IFNAR1 is phosphorylated which in turn phosphorylates Jak1 associated with IFNAR2. This kinase continues its signal transduction by phosphorylation of signal transducer and activator of transcription (STAT) 1 and 2 via Jak 1 and Tyk2 respectively. The phosphorylated STATs then dissociate from the receptor heterodimer and form an interferon transcription factor with p48 and IRF9 to form the interferon stimulate transcription factor-3 (ISGF3). This transcription factor then translocates to the nucleus where it will transcribe several genes involved in cell cycle control, cell differentiation, apoptosis, and immune response.[3][4]

PEG-interferon alpha-2b acts as a multifunctional immunoregulatory cytokine by transcribing several genes, including interleukin 4 (IL4). This cytokine is responsible for inducing T helper cells to become type 2 helper T cells. This ultimately results in the stimulation of B cells to proliferate and increase their antibody production. This ultimately allows for an immune response, as the B cells will help to signal the immune system that a foreign antigen is present.[5]

Another major mechanism of type I interferon alpha (IFNα) is to stimulate apoptosis in malignant cell lines. Previous studies have shown that IFNα can cause cell cycle arrest in U266, Daudi, and Rhek-1 cell lines.[6]

A follow-up study researched to determine if the caspases were involved in the apoptosis seen in the previous study as well as to determine the role of mitochondrial cytochrome c release. The study confirmed that there was cleavage of caspase-3, -8, and -9. All three of these cysteine proteases play an important role in the initiation and activation of the apoptotic cascade. Furthermore, it was shown that IFNα induced a loss in the mitochondrial membrane potential which resulted in the release of cytochrome c from the mitochondria. Follow-up research is currently being conducted to determine the upstream activators of the apoptotic pathway that are induced by IFNα.[7]

Host genetic factors influencing treatment response[edit]

For genotype 1 hepatitis C treated with pegylated interferon-alfa-2a or pegylated interferon-alfa-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in Nature,[8] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more likely to achieve sustained virological response after the treatment than others. A later report from Nature[9] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

See also[edit]



  1. ^ See line 27
  2. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  3. ^ Ward AC, Touw I, Yoshimura A (January 2000). "The Jak-Stat pathway in normal and perturbed hematopoiesis". Blood. 95 (1): 19–29. PMID 10607680. 
  4. ^ PATHWAYS :: IFN alpha
  5. ^ Thomas H, Foster G, Platis D (February 2004). "Corrigendum to Mechanisms of action of interferon and nucleoside analogues J Hepatol 39 (2003) S93–8". J Hepatol. 40 (2): 364. doi:10.1016/j.jhep.2003.12.003. 
  6. ^ Sangfelt O, Erickson S, Castro J, Heiden T, Einhorn S, Grandér D (March 1997). "Induction of apoptosis and inhibition of cell growth are independent responses to interferon-alpha in hematopoietic cell lines". Cell Growth Differ. 8 (3): 343–52. PMID 9056677. 
  7. ^ Thyrell L, Erickson S, Zhivotovsky B, et al. (February 2002). "Mechanisms of Interferon-alpha induced apoptosis in malignant cells". Oncogene. 21 (8): 1251–62. doi:10.1038/sj.onc.1205179. PMID 11850845. 
  8. ^ Ge D, Fellay J, Thompson AJ, et al. (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. doi:10.1038/nature08309. PMID 19684573. 
  9. ^ Thomas DL, Thio CL, Martin MP, et al. (2009). "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature. 461 (7265): 798–801. doi:10.1038/nature08463. PMC 3172006free to read. PMID 19759533. 

External links[edit]