ArticleOncotarget2015
Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 52 citations in OpenAlex.
- Redox-signaling in innate immune memory: Similar mechanisms in animals/humans and plants.Redox biology · 2025Review
- Targeting the NLRP3 inflammasome for inflammatory disease therapy.Trends in pharmacological sciences · 2025Review
- Lost at SCLC: a review of potential platinum sensitizers.Cancer metastasis reviews · 2024Review
- G6PD Orchestrates Genome-Wide DNA Methylation and Gene Expression in the Vascular Wall.International journal of molecular sciences · 2023Article
- A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation.Drugs · 2023Review
- RRx-001: a chimeric triple action NLRP3 inhibitor, Nrf2 inducer, and nitric oxide superagonist.Frontiers in oncology · 2023Review
- The small molecule NLRP3 inhibitor RRx-001 potentiates regorafenib activity and attenuates regorafenib-induced toxicity in mice bearing human colorectal cancer xenografts.American journal of cancer research · 2022Article
- Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer.Frontiers in chemistry · 2022Article
- RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor.Cellular & molecular immunology · 2021Article
- Interactions between metabolism and chromatin in plant models.Molecular metabolism · 2020Review
- Novel Combination Therapies for the Treatment of Bladder Cancer.Frontiers in oncology · 2020Review
- S-nitrosothiols and HRedox biology · 2019Review
- RRx-001 protects normal tissues but not tumors via Nrf2 induction and Bcl-2 inhibition.Journal of cancer research and clinical oncology · 2019Article
- RRx-001 followed by platinum plus etoposide in patients with previously treated small-cell lung cancer.British journal of cancer · 2019Article
- New combinatorial strategies to improve the PARP inhibitors efficacy in the urothelial bladder Cancer treatment.Journal of experimental & clinical cancer research : CR · 2019Review
- CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Novel Nitric Oxide Donors of Phenylsulfonylfuroxan and 3-Benzyl Coumarin Derivatives as Potent Antitumor Agents.ACS medicinal chemistry letters · 2018Article
- The dichotomous role of HBiochemical pharmacology · 2018Review
- Article
- RRx-001 protects against cisplatin-induced toxicities.Journal of cancer research and clinical oncology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RRx-001 is a novel aerospace-derived compound currently under investigation in several ongoing Phase II studies. In a Phase I trial, it demonstrated anti-cancer activity and evidence of resensitization to formerly effective therapies in heavily pre-treated patients with relapsed/refractory solid tumors. RRx-001 generates reactive oxygen and nitrogen species (ROS and RNS) and nitric oxide (NO), elicits changes in intracellular redox status, modulates tumor blood flow, hypoxia and vascular function and triggers apoptosis in cancer cells. We investigated the effect of RRx-001 on the epigenome of SCC VII cancer cells. RRx-001 at 0.5 and 2 μM significantly decreased global DNA methylation, i.e., 5-methylcytosine levels, in SCC VII cells. Consistently, 0.5-5 μM RRx-001 significantly decreased Dnmt1 and Dnmt3a protein expression in a dose- and time-dependent manner. In addition, global methylation profiling identified differentially methylated genes in SCC VII cells treated with 0.5, 2, and 5 μM RRx-001 compared to control cells. Twenty-three target sites were hypomethylated and 22 hypermethylated by >10% in the presence of at least two different concentrations of RRx-001. Moreover, RRx-001 at 2 μM significantly increased global acetylated histone H3 and H4 levels in SCC VII cells after 24 hour treatment, suggesting that RRx-001 regulates global acetylation in cancer cells. These results demonstrate that, in contrast to the traditional "one drug one target" paradigm, RRx-001 has multi(epi)target features, which contribute to its anti-cancer activity and may rationalize the resensitization to previously effective therapies observed in clinical trials and serve as a unifying mechanism for its anticancer activity.
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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.