ArticleACS medicinal chemistry letters2022
An Unexpected Deuterium-Induced Metabolic Switch in Doxophylline.
Article in ACS medicinal chemistry letters, 2022. 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 5 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.
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Who cites it
5 citing papers in PubMed.
- Potential of doxofylline in the treatment of chronic obstructive airway diseases (Review).Biomedical reports · 2025Review
- Designing chemical systems for precision deuteration of medicinal building blocks.Nature communications · 2024Article
- Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers.Scientific reports · 2023Article
- Deuterium in drug discovery: progress, opportunities and challenges.Nature reviews. Drug discovery · 2023Review
- Deuterated Drugs and Biomarkers in the COVID-19 Pandemic.ACS omega · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Precision deuteration has become part of the medicinal chemist's toolbox, but its usefulness can be undermined by unpredictable metabolic switch effects. Herein we report the deuteration of doxophylline, a drug used in the treatment of asthma and COPD that undergoes extensive oxidative metabolism. Labeling of the main metabolic soft spots triggered an unexpected multidirectional metabolic switch that, while not improving the pharmacokinetic parameters, changed the metabolic scenario and, in turn, the pharmacodynamic features in two murine models of lung injury.
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Registered trials
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