ArticleJournal of biomolecular screening2012
Potential repurposing of known drugs as potent bacterial β-glucuronidase inhibitors.
Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- High-throughput identification of bacterial β-glucuronidase inhibitors using machine learning.Gut microbes · 2026Article
- β-glucuronidase inhibitors isolated from the fruit of Forsythia suspensa (Thunb.) Vahl.Journal of natural medicines · 2026Article
- Managing Irinotecan-Induced Diarrhea: A Comprehensive Review of Therapeutic Interventions in Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Design, synthesis, and biological evaluation of (thio)urea derivatives as potentJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Targeting the human gut microbiome with small-molecule inhibitors.Nature reviews. Chemistry · 2023Review
- Phenelzine and Amoxapine Inhibit Tyramine and d-Glucuronic Acid Catabolism in Clinically SignificantPathogens (Basel, Switzerland) · 2021Article
- Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy.Frontiers in cellular and infection microbiology · 2021Review
- Therapeutic significance of β-glucuronidase activity and its inhibitors: A review.European journal of medicinal chemistry · 2020Review
- Gut Microbial β-Glucuronidase Inhibition via Catalytic Cycle Interception.ACS central science · 2018Article
- Article
- Real-time imaging of intestinal bacterial β-glucuronidase activity by hydrolysis of a fluorescent probe.Scientific reports · 2017Article
- Preventive Effects of a Chinese Herbal Formula, Shengjiang Xiexin Decoction, on Irinotecan-Induced Delayed-Onset Diarrhea in Rats.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Gut microbiome interactions with drug metabolism, efficacy, and toxicity.Translational research : the journal of laboratory and clinical medicine · 2017Review
- The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism.Nature reviews. Microbiology · 2016Review
- Discovery of specific inhibitors for intestinal E. coli β-glucuronidase through in silico virtual screening.TheScientificWorldJournal · 2015Article
- Old drug new use--amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Therapeutic targeting of CPT-11 induced diarrhea: a case for prophylaxis.Current drug targets · 2013Review
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 1 institution in 1 country.
Funding
Abstract
The active metabolite of the chemotherapeutic irinotecan, SN-38, is detoxified through glucuronidation and then excreted into the gastrointestinal tract. Intestinal bacteria convert the glucuronidated metabolite back to the toxic SN-38 using β-glucuronidase (GUS), resulting in debilitating diarrhea. Inhibiting GUS activity may relieve this side effect of irinotecan. In this study, we sought to determine whether any known drugs have GUS inhibitory activity. We screened a library of Food and Drug Administration-approved drugs with a cell-free biochemical enzyme assay using purified bacterial GUS. After triage, five drugs were confirmed to inhibit purified bacterial GUS. Three of these were the monoamine oxidase inhibitors nialamide, isocarboxazid, and phenelzine with average IC(50) values for inhibiting GUS of 71, 128, and 2300 nM, respectively. The tricyclic antidepressant amoxapine (IC(50) = 388 nM) and the antimalarial mefloquine (IC(50) = 1.2 µM) also had activity. Nialamide, isocarboxazid, and amoxapine had no significant activity against purified mammalian GUS but showed potent activity for inhibiting endogenous GUS activity in a cell-based assay using living intact Escherichia coli with average IC(50) values of 17, 336, and 119 nM, respectively. Thus, nialamide, isocarboxazid, and amoxapine have potential to be repurposed as therapeutics to reduce diarrhea associated with irinotecan chemotherapy and warrant further investigation for this use.
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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.