ArticleMolecular pharmaceutics
Serine peptide phosphoester prodrugs of cyclic cidofovir: synthesis, transport, and antiviral activity.
Article in Molecular pharmaceutics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 37 citations in OpenAlex.
- Monkeypox: Origin, Transmission, Clinical Manifestations, Prevention, and Therapeutic Options.Interdisciplinary perspectives on infectious diseases · 2025Review
- Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases.Biomolecules · 2024Article
- Mpox (formerly monkeypox): pathogenesis, prevention, and treatment.Signal transduction and targeted therapy · 2023Review
- Phosphoryl Prodrugs: Characteristics to Improve Drug Development.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.Frontiers in chemistry · 2022Review
- Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold.Frontiers in chemistry · 2022Review
- Overview of Biologically Active Nucleoside Phosphonates.Frontiers in chemistry · 2020Review
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- Evolution of an amino acid based prodrug approach: stay tuned.Molecular pharmaceutics · 2013Article
- Transporter-targeted lipid prodrugs of cyclic cidofovir: a potential approach for the treatment of cytomegalovirus retinitis.Journal of pharmaceutical sciences · 2012Article
- Synthesis of a phosphoserine mimetic prodrug with potent 14-3-3 protein inhibitory activity.Chemistry & biology · 2012Article
- Structure of cyclic nucleoside phosphonate ester prodrugs: an inquiry.The Journal of organic chemistry · 2012Article
- Cytomegalovirus antivirals and development of improved animal models.Expert opinion on drug metabolism & toxicology · 2011Review
- Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.Journal of medicinal chemistry · 2011Article
- Synthesis, transport and antiviral activity of Ala-Ser and Val-Ser prodrugs of cidofovir.Bioorganic & medicinal chemistry letters · 2011Article
- Approaches to tyrosine-linked peptidomimetic prodrugs of (S)-HPMP-based acyclic nucleoside phosphonates.Phosphorus, sulfur, and silicon and the related elements · 2011Article
- Comparison of the safety and pharmacokinetics of ST-246® after i.v. infusion or oral administration in mice, rabbits and monkeys.PloS one · 2011Article
- Serine side chain-linked peptidomimetic conjugates of cyclic HPMPC and HPMPA: synthesis and interaction with hPEPT1.Molecular pharmaceutics · 2010Article
- Synthesis of peptidomimetic conjugates of cyclic nucleoside phosphonates.Current protocols in nucleic acid chemistry · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Cidofovir (HPMPC, 1), a broad-spectrum antiviral agent, is currently used to treat AIDS-related human cytomegalovirus (HCMV) retinitis and has recognized therapeutic potential for orthopox virus infections, but is limited by its low oral bioavailability. Cyclic cidofovir (2) displays decreased nephrotoxicity compared to 1, while also exhibiting potent antiviral activity. Here we describe in detail the synthesis and evaluation as prodrugs of four cHPMPC dipeptide conjugates in which the free POH of 2 is esterified by the Ser side chain alcohol group of an X-L-Ser(OMe) dipeptide: 3 (X=L-Ala), 4 (X=L-Val), 5 (X=L-Leu), and 6 (X=L-Phe). Perfusion studies in the rat establish that the mesenteric permeability to 4 is more than 20-fold greater than to 1, and the bioavailability of 4 is increased 6-fold relative to 1 in an in vivo murine model. In gastrointestinal and liver homogenates, the cHPMPC prodrugs are rapidly hydrolyzed to 2. Prodrugs 3, 4, and 5 are nontoxic at 100 microM in HFF and KB cells and in cell-based plaque reduction assays had IC 50 values of 0.1-0.5 microM for HCMV and 10 microM for two orthopox viruses (vaccinia and cowpox). The enhanced transport properties of 3-6, conferred by incorporation of a biologically benign dipeptide moiety, and the facile cleavage of the Ser-O-P linkage suggest that these prodrugs represent a promising new approach to enhancing the bioavailability of 2.
Indexed as
Identifiers
What OpenQuestion holds
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.