ArticleMalaria journal2015
From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria.
Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Identification of the disulfidptosis-related gene G6PD as a potential biomarker and therapeutic target in pancreatic ductal adenocarcinoma by integrative bioinformatics analysis and experimental validation.Discover oncology · 2026Article
- Impact of Growth Conditions on High-Throughput Identification of Repurposing Drugs forAntibiotics (Basel, Switzerland) · 2024Article
- 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
- RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway.Frontiers in pharmacology · 2022Article
- 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
- Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections.F1000Research · 2021Review
- Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19.Seminars in oncology · 2020Article
- The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia-reperfusion injury.Expert review of hematology · 2017Article
- Rat red blood cell storage lesions in various additive solutions.Clinical hemorheology and microcirculation · 2017Article
- A look inside the mechanistic black box: Are red blood cells the critical effectors of RRx-001 cytotoxicity?Medical oncology (Northwood, London, England) · 2016Article
- Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.Free radical biology & medicine · 2016Article
- Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundThe survival of malaria parasites, under substantial haem-induced oxidative stress in the red blood cells (RBCs) is dependent on the pentose phosphate pathway (PPP). The PPP is the only source of NADPH in the RBC, essential for the production of reduced glutathione (GSH) and for protection from oxidative stress. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, therefore, increases the vulnerability of erythrocytes to oxidative stress. In Plasmodium, G6PD is combined with the second enzyme of the PPP to create a unique bifunctional enzyme, named glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (G6PD-6PGL). RRx-001 is a novel, systemically non-toxic, epigenetic anticancer agent currently in Phase 2 clinical development for multiple tumour types, with activity mediated through increased nitric oxide (NO) production and PPP inhibition. The inhibition of G6PD and NO overproduction induced by RRx-001 suggested its application in cerebral malaria (CM).
methodsPlasmodium berghei ANKA (PbA) infection in C57BL/6 mice is an experimental model of cerebral malaria (ECM) with several similar pathological features to human CM. This study uses intravital microscopy methods with a closed cranial window model to quantify cerebral haemodynamic changes and leukocyte adhesion to endothelial cells in ECM.
resultsRRx-001 had both single agent anti-parasitic activity and significantly increased the efficacy of artemether. In addition, RRx-001 preserved cerebral perfusion and reduced inflammation alone or combined with artemether. RRx-001's effects were associated with inhibition of PPP (G6PD and G6PD-6PGL) and by improvements in microcirculatory flow, which may be related to the NO donating properties of RRx-001.
conclusionThe results indicate that RRx-001 could be used to potentiate the anti-malarial action of artemisinin, particularly on resistant strains, and to prevent infection.
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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.