Metabolism of Nucleosides and Nucleotides Prodrugs

Title:Metabolism of Nucleosides and Nucleotides Prodrugs

Volume: 23 Issue: 45

Author(s): Coralie De Schutter, Maryam Ehteshami, Emily T. Hammond, Franck Amblard and Raymond F. Schinazi*

Affiliation:

• Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta,United States

Keywords: Antiviral agents, prodrug, nucleoside, enzyme, monophosphate, triphosphate.

Abstract: Background: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form.

Methods: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with different groups that can be intracellularly cleaved either chemically or enzymatically.

Results: Several prodrug approaches have been successfully developed in order to increase the efficacy, bioavailability, penetration in target organ, and selectivity of nucleoside/nucleotide analogs.

Conclusion: The concept of nucleoside/nucleotide prodrug is now a well-established approach that led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and cancer.

Cite this article as:

De Schutter Coralie, Ehteshami Maryam, Hammond T. Emily, Amblard Franck and Schinazi F. Raymond *, Metabolism of Nucleosides and Nucleotides Prodrugs, Current Pharmaceutical Design 2017; 23 (45) . https://dx.doi.org/10.2174/1381612823666171011104158