ArticleBioorganic chemistry2021
Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.
Article in Bioorganic chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 16 citations in OpenAlex.
- Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor.Frontiers in immunology · 2025Review
- Tryptophan Indole Derivatives: Key Players in Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Discrete interplay of gut microbiota L-tryptophan metabolites in host biology and disease.Molecular and cellular biochemistry · 2024Review
- Tryptophan metabolites and incident cardiovascular disease: The EPIC-Norfolk prospective population study.Atherosclerosis · 2023Article
- Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity.International journal of molecular sciences · 2022Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Diverse roles of microbial indole compounds in eukaryotic systems.Biological reviews of the Cambridge Philosophical Society · 2021Review
- Profiling Tryptophan Catabolites of Human Gut Microbiota and Acute-Phase Protein Levels in Neonatal Dried Blood Specimens.Frontiers in microbiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
Microbial metabolite mimicry is a new concept that promises to deliver compounds that have minimal liabilities and enhanced therapeutic effects in a host. In a previous publication, we have shown that microbial metabolites of L-tryptophan, indoles, when chemically altered, yielded potent anti-inflammatory pregnane X Receptor (PXR)-targeting lead compounds, FKK5 and FKK6, targeting intestinal inflammation. Our aim in this study was to further define structure-activity relationships between indole analogs and PXR, we removed the phenyl-sulfonyl group or replaced the pyridyl residue with imidazolopyridyl of FKK6. Our results showed that while removal of the phenyl-sulfonyl group from FKK6 (now called CVK003) shifts agonist activity away from PXR towards the aryl hydrocarbon receptor (AhR), the imidazolopyridyl addition preserves PXR activity in vitro. However, when these compounds are administered to mice, that unlike the parent molecule, FKK6, they exhibit poor induction of PXR target genes in the intestines and the liver. These data suggest that modifications of FKK6 specifically in the pyridyl moiety can result in compounds with weak PXR activity in vivo. These observations are a significant step forward for understanding the structure-activity relationships (SAR) between indole mimics and receptors, PXR and AhR.
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.