ArticleAntimicrobial agents and chemotherapy2007
Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art.Antiviral research · 2009Trial
- Next-Generation Lipid Prodrugs Orally Deliver Tenofovir via Enhanced Chylomicron Incorporation.ACS pharmacology & translational science · 2025Article
- Building Metabolically Stable and Potent Anti-HIV Thioether-Lipid Analogues of Tenofovir Exalidex: A thorough Pharmacological Analysis.Journal of medicinal chemistry · 2024Article
- The Application of Prodrugs as a Tool to Enhance the Properties of Nucleoside Reverse Transcriptase Inhibitors.Viruses · 2023Review
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- The progress of molecules and strategies for the treatment of HBV infection.Frontiers in cellular and infection microbiology · 2023Review
- Expanding the toolbox of metabolically stable lipid prodrug strategies.Frontiers in pharmacology · 2022Article
- Advance of structural modification of nucleosides scaffold.European journal of medicinal chemistry · 2021Review
- Investigational drugs with dual activity against HBV and HIV (Review).Experimental and therapeutic medicine · 2021Review
- HBV replication inhibitors.Antiviral research · 2020Review
- Overview of Biologically Active Nucleoside Phosphonates.Frontiers in chemistry · 2020Review
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
- The cyclophilin inhibitor CRV431 inhibits liver HBV DNA and HBsAg in transgenic mice.PloS one · 2019Article
- Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases.Future medicinal chemistry · 2019Review
- Validation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugs.Journal of pharmaceutical and biomedical analysis · 2018Article
- Towards HBV curative therapies.Liver international : official journal of the International Association for the Study of the Liver · 2018Review
- New Viral and Immunological Targets for Hepatitis B Treatment and Cure: A Review.Infectious diseases and therapy · 2017Review
- Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.Molecules (Basel, Switzerland) · 2017Review
- Next-Generation Reduction Sensitive Lipid Conjugates of Tenofovir: Antiviral Activity and Mechanism of Release.Journal of medicinal chemistry · 2016Article
- Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis, Stability, and Antiviral Activity.Journal of medicinal chemistry · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
9-R-[2-(Phosphonomethoxy)propyl]-adenine (tenofovir) is an acyclic nucleoside phosphonate with antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). Tenofovir is not orally bioavailable but becomes orally active against HIV-1 infection as the disoproxil ester (tenofovir disoproxil fumarate [Viread]). We have developed an alternative strategy for promoting the oral availability of nucleoside phosphonate analogs which involves esterification with a lipid to form a lysolecithin mimic. This mimic can utilize natural lysolecithin uptake pathways in the gut, resulting in high oral availability. Since the mimic is not subject to cleavage in the plasma by nonspecific esterases, it remains intact in the circulation and facilitates uptake by target cells. Significant drops in apparent antiviral 50% effective concentrations (EC(50)s) of up to 3 logs have been observed in comparison with non-lipid-conjugated parent compounds in target cells. We have applied this technology to tenofovir with the goal of increasing oral availability, decreasing the apparent EC(50), and decreasing the potential for nephrotoxicity by reducing the exposure of the kidney to the free dianionic tenofovir. Here we report that, in vitro, the hexadecyloxypropyl ester of tenofovir, CMX157, is 267-fold more active than tenofovir against HIV-1 and 4.5-fold more active against HBV. CMX157 is orally available and has no apparent toxicity when given orally to rats for 7 days at doses of 10, 30, or 100 mg/kg/day. Consequently, CMX157 represents a second-generation tenofovir analog which may have an improved clinical profile.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.