ArticleInternational journal of radiation oncology, biology, physics2011
Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators.
Article in International journal of radiation oncology, biology, physics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 65 citations in OpenAlex.
- Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death.Science translational medicine · 2011Trial
- Targeting Mitochondrial Reactive Oxygen Species: JP4-039's Potential as a Cardiovascular Therapeutic.Journal of clinical medicine · 2025Review
- Nitroxides: Chemistry, Antioxidant Properties, and Biomedical Applications.Molecules (Basel, Switzerland) · 2025Review
- Oxidant-Dependent Sensitizing, Protective, and Mitigative Effects in X-Ray-Irradiated Pulmonary Endothelial Cells.The Journal of pharmacology and experimental therapeutics · 2024Article
- Combined injury: irradiation with skin or bone wounds in rodent models.Journal of radiological protection : official journal of the Society for Radiological Protection · 2021Article
- Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase.Antioxidants (Basel, Switzerland) · 2021Review
- Using Zebrafish as a Disease Model to Study Fibrotic Disease.International journal of molecular sciences · 2021Review
- "Longitudinal Fecal Microbiome Study of Total Body Irradiated Mice Treated With Radiation Mitigators Identifies Bacterial Associations With Survival".Frontiers in cellular and infection microbiology · 2021Article
- Anti-Ferroptosis Drug Enhances Total-Body Irradiation Mitigation by Drugs that Block Apoptosis and Necroptosis.Radiation research · 2020Article
- Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.Journal of cell communication and signaling · 2019Review
- Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Amelioration of Head and Neck Radiation-Induced Mucositis and Distant Marrow Suppression in FancaRadiation research · 2018Article
- Liquid chromatography-tandem mass spectrometric assay for the quantitation of the novel radiation protective agent and radiation mitigator JP4-039 in murine plasma.Journal of pharmaceutical and biomedical analysis · 2018Article
- Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum-mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients with complex I deficiency.Scientific reports · 2018Article
- Improved Total-Body Irradiation Survival by Delivery of Two Radiation Mitigators that Target Distinct Cell Death Pathways.Radiation research · 2018Article
- Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.Chemical reviews · 2017Review
- Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays.International journal of molecular sciences · 2017Article
- Effectiveness of Analogs of the GS-Nitroxide, JP4-039, as Total Body Irradiation Mitigators.In vivo (Athens, Greece) · 2017Article
- A Mitochondrial-Targeted Nitroxide Is a Potent Inhibitor of Ferroptosis.ACS central science · 2016Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeTo evaluate the effectiveness of mitigation of acute ionizing radiation damage by mitochondrion-targeted small molecules. METHODS AND MATERIALS: We evaluated the ability of nitroxide-linked alkene peptide isostere JP4-039, the nitric oxide synthase inhibitor-linked alkene peptide esostere MCF201-89, and the p53/mdm2/mdm4 protein complex inhibitor BEB55 to mitigate radiation effects by clonogenic survival curves with the murine hematopoietic progenitor cell line 32D cl 3 and the human bone marrow stromal (KM101) and pulmonary epithelial (IB3) cell lines. The p53-dependent mechanism of action was tested with p53(+/+) and p53(-/-) murine bone marrow stromal cell lines. C57BL/6 NHsd female mice were injected i.p. with JP4-039, MCF201-89, or BEB55 individually or in combination, after receiving 9.5 Gy total body irradiation (TBI).
resultsEach drug, JP4-039, MCF201-89, or BEB55, individually or as a mixture of all three compounds increased the survival of 32D cl 3 (p = 0.0021, p = 0.0011, p = 0.0038, and p = 0.0073, respectively) and IB3 cells (p = 0.0193, p = 0.0452, p = 0.0017, and p = 0.0019, respectively) significantly relative to that of control irradiated cells. KM101 cells were protected by individual drugs (p = 0.0007, p = 0.0235, p = 0.0044, respectively). JP4-039 and MCF201-89 increased irradiation survival of both p53(+/+) (p = 0.0396 and p = 0.0071, respectively) and p53(-/-) cells (p = 0.0007 and p = 0.0188, respectively), while BEB55 was ineffective with p53(-/-) cells. Drugs administered individually or as a mixtures of all three after TBI significantly increased mouse survival (p = 0.0234, 0.0009, 0.0052, and 0.0167, respectively).
conclusionMitochondrial targeting of small molecule radiation mitigators decreases irradiation-induced cell death in vitro and prolongs survival of lethally irradiated mice.
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