Trial reportToxicology and applied pharmacology2013
Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo.
Trial report in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00621309 (Phase I Clinical Trial to Evaluate the Efficacy of Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions), which is not on this map. Cited by 26 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.
Phase I Clinical Trial to Evaluate the Efficacy of Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions
Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Modulation of Obesity-Related Lipid Metabolism by Sulforaphane Through AMPK-Centered Molecular Networks.International journal of molecular sciences · 2026Review
- Sulforaphane Synergies with Phytochemicals and Pharmaceuticals: Implications for Healthspan.Medicines (Basel, Switzerland) · 2026Review
- Downregulation of hepatic CYP3A isoforms by bardoxolone methyl in rats and its impact on in vivo metabolic capacity reflecting pharmacokinetics.Scientific reports · 2026Article
- Review
- Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Design and Optimization of 1Journal of medicinal chemistry · 2022Article
- Article
- Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy.Stem cell reports · 2022Article
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- The Challenges of Designing and Implementing Clinical Trials With Broccoli Sprouts… and Turning Evidence Into Public Health Action.Frontiers in nutrition · 2021Review
- An Overview of Registered Clinical Trials on Glucosinolates and Human Health: The Current Situation.Frontiers in nutrition · 2021Review
- Current Landscape of NRF2 Biomarkers in Clinical Trials.Antioxidants (Basel, Switzerland) · 2020Review
- Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer.Medicinal research reviews · 2020Review
- Broccoli or Sulforaphane: Is It the Source or Dose That Matters?Molecules (Basel, Switzerland) · 2019Review
- Belinostat, at Its Clinically Relevant Concentrations, Inhibits Rifampicin-Induced CYP3A4 and MDR1 Gene Expression.Molecular pharmacology · 2019Article
- KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane.Trends in food science & technology · 2017Article
- SPA70 is a potent antagonist of human pregnane X receptor.Nature communications · 2017Article
- Small-molecule modulators of PXR and CAR.Biochimica et biophysica acta · 2016Review
- A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?Current pharmacology reports · 2016Article
- Ginkgolide B protects human umbilical vein endothelial cells against xenobiotic injuries via PXR activation.Acta pharmacologica Sinica · 2016Article
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 3 institutions in 1 country.
Funding
Abstract
Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand - rifampicin (300mg/d) was given alone for 7days in arm 1, or in daily combination with 450μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology.
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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.