ArticleDrug metabolism and disposition: the biological fate of chemicals2025
Impact of the loss of slc43a3 on 6-mercaptopurine absorption and tissue distribution in mice.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed.
- Mass Spectrometric Detected Cancer Proteins as Resources for Cancer Research.Journal of proteome research · 2026Article
- Computational exploration of anticancer drug adsorption on a porous organic nanocage: Insights from density functional theory for targeted nanocarrier design.Scientific reports · 2026Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
6-Mercaptopurine (6-MP) is a nucleobase analog used in the therapy of acute lymphoblastic leukemia and inflammatory bowel disease. It is associated with numerous side effects including myelotoxicity, hepatotoxicity, and gastrointestinal complications, which can lead to patient adherence issues or discontinuation of treatment. This is further complicated by the wide variability in plasma levels of 6-MP and the therapeutic response to a standard dose. Although a number of enzyme polymorphisms have been linked to therapeutic response, it is unclear what factors underlie the variability in plasma levels. We have established that SLC43A3-encoded equilibrative nucleobase transporter 1 mediates the transport of 6-MP into cells in both mice and humans. To determine whether this transporter is critical for 6-MP absorption and biodistribution, we examined the effect of the genetic deletion of slc43a3 in mice on the absorption and tissue distribution of orally administered 6-MP. A high-performance liquid chromatography method was developed to measure tissue levels of 6-MP and its key metabolites, 6-methylmercaptoprine, 6-thiourate, and 6-thioguanine nucleotides. The results of this study show that loss of slc43a3 dramatically reduces the absorption of 6-MP from the gastrointestinal tract and attenuates the levels achieved in peripheral tissues. Furthermore, the loss of slc43a3 decreases the tissue:blood concentration ratios of 6-MP and its metabolites, particularly in those tissues that show high levels of expression of slc43a3, such as the heart and lungs. Therefore, it is possible that differences in SLC43A3 expression in humans may contribute to the variability seen in 6-MP plasma levels and therapeutic response. SIGNIFICANCE STATEMENT: The loss of slc43a3 in mice dramatically reduces the absorption and the biodistribution of the chemotherapeutic drug 6-mercaptopurine. These data suggest that variations in SLC43A3 expression in humans may contribute to the variability in plasma levels that have been reported when using this drug therapeutically.
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.