Abstract |
Celgosivir, in development by MIGENIX Inc for the treatment of HCV infection, is an oral prodrug of the natural product castanospermine that inhibits alpha-glucosidase I, an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked oligosaccharides of viral envelope glycoproteins. Celgosivir is well absorbed in vitro and in vivo, and is rapidly converted to castanospermine. Celgosivir has a novel mechanism of action (ie, host-directed glycosylation), and demonstrates broad antiviral activity in vitro. The agent is not efficient as a monotherapy for the treatment of HCV, but has demonstrated a synergistic effect in combination with the current standard of care, PEGylated IFNalpha2b plus ribavirin, both in vitro and in phase II clinical trials. At the time of publication, a phase II trial was underway to investigate the safety, tolerability and antiviral effect of celgosivir in combination with PEGylated IFNalpha2b plus ribavirin for up to 1 year in patients with chronic HCV infection. Celgosivir may prove to be a valuable component for combination therapy and may help to prevent the apparition of drug resistance. Long-term toxicity studies are necessary to confirm the safety of this novel drug in humans.
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Authors | David Durantel |
Journal | Current opinion in investigational drugs (London, England : 2000)
(Curr Opin Investig Drugs)
Vol. 10
Issue 8
Pg. 860-70
(Aug 2009)
ISSN: 2040-3429 [Electronic] England |
PMID | 19649930
(Publication Type: Journal Article, Review)
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Chemical References |
- Antiviral Agents
- Glycoside Hydrolase Inhibitors
- Indolizines
- Interferon alpha-2
- Interferon-alpha
- Prodrugs
- Recombinant Proteins
- Polyethylene Glycols
- Ribavirin
- celgosivir
- glucosidase I
- alpha-Glucosidases
- peginterferon alfa-2b
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Topics |
- Animals
- Antiviral Agents
(pharmacokinetics, pharmacology, therapeutic use)
- Clinical Trials as Topic
- Drug Synergism
- Drug Therapy, Combination
- Glycoside Hydrolase Inhibitors
- Hepacivirus
(drug effects)
- Hepatitis C, Chronic
(drug therapy)
- Humans
- Indolizines
(pharmacokinetics, pharmacology, therapeutic use)
- Interferon alpha-2
- Interferon-alpha
(therapeutic use)
- Polyethylene Glycols
(therapeutic use)
- Prodrugs
(pharmacokinetics, pharmacology, therapeutic use)
- Recombinant Proteins
- Ribavirin
(therapeutic use)
- alpha-Glucosidases
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