ArticleACS chemical biology2019
Targeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 62 citations in OpenAlex.
- Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis.Cell reports. Medicine · 2021Trial
- High-throughput identification of bacterial β-glucuronidase inhibitors using machine learning.Gut microbes · 2026Article
- Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.Microorganisms · 2026Review
- Engineering human Gut-on-a-Chip culturomics for predictive pharmacomicrobiomics of first-pass metabolism.npj biomedical innovations · 2026Review
- Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026Review
- Phenotypic high-throughput screening identifies modulators of gut microbial choline metabolism.mBio · 2026Article
- Harnessing the microbiome: unveiling the influence of the gut microbiota on hepatobiliary cancer therapeutic strategies.Clinical and molecular hepatology · 2026Review
- Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The role of the gut microbiota in chemotherapy response, efficacy and toxicity: a systematic review.NPJ precision oncology · 2025Article
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- Microbiome-derived reactivation of mycophenolate explains variations in enterohepatic recirculation in kidney transplant recipients.Microbiome · 2025Article
- From Bones to Bugs: Structure-Based Development of Raloxifene-Derived Pathoblockers That Inhibit Pyocyanin Production inJournal of medicinal chemistry · 2025Article
- The role of gut microbial β-glucuronidases in carcinogenesis and cancer treatment: a scoping review.Journal of cancer research and clinical oncology · 2024Article
- Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity.RSC chemical biology · 2024Article
- Bipyraloxifene - a modified raloxifene vector against triple-negative breast cancer.RSC medicinal chemistry · 2024Article
- Gut microbial β-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.Cell host & microbe · 2024Article
- Integrating the gut microbiome and pharmacology.Science translational medicine · 2024Review
- Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib.Theranostics · 2024Article
- Drug-microbiota interactions: an emerging priority for precision medicine.Signal transduction and targeted therapy · 2023Review
- Microbial β-glucuronidases drive human periodontal disease etiology.Science advances · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Regorafenib (Stivarga) is an oral small molecule kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from the reactivation of the inactive regorafenib-glucuronide to regorafenib by gut microbial β-glucuronidase (GUS) enzymes in the gastrointestinal tract. We sought to unravel the molecular basis of regorafenib-glucuronide processing by human intestinal GUS enzymes and to examine the potential inhibition of these enzymes. Using a panel of 31 unique gut microbial GUS enzymes derived from the 279 mapped from the human gut microbiome, we found that only four were capable of regorafenib-glucuronide processing. Using crystal structures as a guide, we pinpointed the molecular features unique to these enzymes that confer regorafenib-glucuronide processing activity. Furthermore, a pilot screen identified the FDA-approved drug raloxifene as an inhibitor of regorafenib reactivation by the GUS proteins discovered. Novel synthetic raloxifene analogs exhibited improved potency in both
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.