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• W2104373350 startingPage "223" @default.
• W2104373350 abstract "Over 25 drugs have been approved for the treatment of HIV-1 replication. All but one of these drugs is delivered as an oral medication. Previous studies have demonstrated that two drugs, decitabine and gemcitabine, have potent anti-HIV-1 activities and can work together in synergy to reduce HIV-1 infectivity via lethal mutagenesis. For their current indications, decitabine and gemcitabine are delivered intravenously.As an initial step towards the clinical translation of these drugs for the treatment of HIV-1 infection, we synthesized decitabine and gemcitabine prodrugs in order to increase drug permeability, which has generally been shown to correlate with increased bioavailability in vivo. In the present study we investigated the permeability, stability and anti-HIV-1 activity of decitabine and gemcitabine prodrugs and selected the divalerate esters of each as candidates for further investigation.Our results provide the first demonstration of divalerate prodrugs of decitabine and gemcitabine that are readily permeable, stable and possess anti-HIV-1 activity.These observations predict improved oral availability of decitabine and gemcitabine, and warrant further study of their ability to reduce HIV-1 infectivity in vivo." @default.
• W2104373350 created "2016-06-24" @default.
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• W2104373350 creator A5051464066 @default.
• W2104373350 creator A5058589652 @default.
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• W2104373350 date "2014-12-01" @default.
• W2104373350 modified "2023-09-23" @default.
• W2104373350 title "Characterization of Permeability, Stability and Anti-HIV-1 Activity of Decitabine and Gemcitabine Divalerate Prodrugs" @default.
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• W2104373350 doi "https://doi.org/10.3851/imp2682" @default.
• W2104373350 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4489529" @default.
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• W2104373350 hasPublicationYear "2014" @default.
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