ArticleMedical oncology (Northwood, London, England)2016
Targeting tumor hypoxia with the epigenetic anticancer agent, RRx-001: a superagonist of nitric oxide generation.
Article in Medical oncology (Northwood, London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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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.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Dissecting the opposing regulatory functions of endogenous nitric oxide production in colorectal cancer initiation, adaptive immune response alterations, and ferroptosis execution.Oncology reviews · 2025Review
- Anti-tumor and anti-metastatic effects of RRx-001 on hepatocellular carcinoma: mechanisms of action and therapeutic potential.Frontiers in pharmacology · 2024Article
- RRx-001: a chimeric triple action NLRP3 inhibitor, Nrf2 inducer, and nitric oxide superagonist.Frontiers in oncology · 2023Review
- Clinical Course of Two Patients with COVID-19 Respiratory Failure After Administration of the Anticancer Small Molecule, RRx-001.International medical case reports journal · 2022Article
- Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19.Seminars in oncology · 2020Article
- RRx-001, a first-in-class small molecule inhibitor of MYC and a downregulator of CD47, is an "erythrophagoimmunotherapeutic".Oncoimmunology · 2020Article
- Platelet inhibitory effects of the Phase 3 anticancer and normal tissue cytoprotective agent, RRx-001.Journal of cellular and molecular medicine · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study reveals a novel interaction between deoxyhemoglobin, nitrite and the non-toxic compound, RRx-001, to generate supraphysiologic levels of nitric oxide (NO) in blood. We characterize the nitrite reductase activity of deoxyhemoglobin, which in the presence of bound RRx-001 reduces nitrite at a much faster rate, leading to markedly increased NO generation. These data expand on the paradigm that hemoglobin generates NO via nitrite reduction during hypoxia and ischemia when nitric oxide synthase (NOS) function is limited. Here, we demonstrate that RRx-001 greatly enhances NO generation from nitrite reduction. RRx-001 is thus the first example of a functional superagonist for nitrite reductase. We hypothesize that physiologically this reaction releases the potentially cytotoxic effector NO selectively in hypoxic tumor regions. It may be that a binary NO-H2O2 trigger is indirectly responsible for the observed tumoricidal activity of RRx-001 since NO is known to inhibit mitochondrial respiration.
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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.