N-Terminally PEGylated Human Interferon-β-1a with Improved Pharmacokinetic Properties and in Vivo Efficacy in a Melanoma Angiogenesis Model
Aldehydes
0303 health sciences
Neovascularization, Pathologic
Metabolic Clearance Rate
Melanoma, Experimental
Mice, Nude
Interferon-beta
Antiviral Agents
Cell Line
Polyethylene Glycols
Rats
3. Good health
Mice
03 medical and health sciences
Cell Line, Tumor
Animals
Humans
Female
Encephalomyocarditis virus
Interferon beta-1a
Neoplasm Transplantation
Cell Proliferation
Half-Life
DOI:
10.1021/bc050237q
Publication Date:
2006-01-18T05:21:07Z
AUTHORS (16)
ABSTRACT
PEGylation of IFN-α has been used successfully to improve the pharmacokinetic properties and efficacy drug. To prepare a PEGylated form human interferon-β-1a (IFN-β-1a) suitable for testing in vivo, we have synthesized 20 kDa mPEG-O-2-methylpropionaldehyde it modify N-terminal α-amino group cytokine. The protein retained ∼50% activity unmodified had significantly improved following intravenous administration rats. clearance volume distribution at steady state were reduced ∼30-fold ∼4-fold, respectively, resulting significant increase systemic exposure as determined by area under curve. elimination half-life was ∼13-fold greater than protein. proteins tested their ability inhibit formation radially oriented blood vessels entering periphery SK-MEL-1 melanoma tumors athymic nude homozygous (nu/nu) mice. In single dose comparison study, 1 × 106 units IFN-β-1a resulted 29% reduction vessel number, while 58% reduction. Both treatments statistically reductions mean number compared vehicle (control)-treated mice, with IFN-β-1a-treated mice showing multiple versus daily 9 days 51% 66% vehicle-treated Therefore, modified translated into efficacy. Since IFN-β is treatment sclerosis hepatitis C virus infection, such mPEG-O-2-methylpropionaldehyde-modified may serve useful adjunct these diseases. addition, antiangiogenic effects be harnessed certain cancers, either sole agent or combination other antitumor drugs.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (53)
CITATIONS (132)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....