ArticleAntimicrobial agents and chemotherapy2009
Retention of metabolites of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine, a novel anti-human immunodeficiency virus type 1 thymidine analog, in cells.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed, 9 citations in OpenAlex.
- Advance of structural modification of nucleosides scaffold.European journal of medicinal chemistry · 2021Review
- Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases.Nature reviews. Drug discovery · 2013Review
- From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir.Current pharmaceutical design · 2013Review
- Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile.Antimicrobial agents and chemotherapy · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T), a novel thymidine analog, has more potent anti-human immunodeficiency virus type 1 (HIV-1) activity than its progenitor, stavudine (d4T). The profile of the intracellular metabolites of 4'-Ed4T was qualitatively similar to that of zidovudine (AZT) but not to that of d4T, while after drug removal it showed more persistent anti-HIV activity than AZT or d4T in cell culture. When CEM cells were exposed to various concentrations of 4'-Ed4T, 4'-Ed4T was efficiently taken up by the cells and was readily phosphorylated to 4'-Ed4T monophosphate (4'-Ed4TMP), 4'-Ed4T diphosphate (4'-Ed4TDP), and 4'-Ed4T triphosphate (4'-Ed4TTP). Most importantly, 4'-Ed4TTP, the active metabolite of 4'-Ed4T, persisted significantly longer than 4'-Ed4TDP and 4'-Ed4TMP after drug removal. We further investigated the efflux profiles of 4'-Ed4T in the comparison with those of AZT in CEM cells. After drug removal, both 4'-Ed4T and AZT were effluxed from the cells in a time- and temperature-dependent manner. However, the efflux of 4'-Ed4T from cells was much less efficient than that of AZT. 4'-Ed4T was effluxed from cells only in its nucleoside form, while AZT was effluxed from cells in both its nucleoside and monophosphate forms. The mechanism-of-action study showed that the efflux of 4'-Ed4T or AZT nucleoside might be due to unknown nucleoside transporters which were not related to the equilibrative nucleoside transporters, while the efflux of AZT monophosphate might be due to multidrug resistance protein 4 (MRP4/ABCC4). The results demonstrated that no detectable 4'-Ed4TMP efflux and the less efficient efflux of 4'-Ed4T nucleoside from cells might be one of the biochemical determinants of its persistent antiviral activity in cell culture.
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.