Effectiveness of Analogs of the GS-Nitroxide, JP4-039, as Total Body Irradiation Mitigators
| Autor: | Joel S. Greenberger, Michael W. Epperly, Joshua R. Sacher, Tanja Krainz, Xiaolin Zhang, Renee Fisher, Peter Wipf, Mary Liang, Hong Wang, Song Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Nitroxide mediated radical polymerization Whole body irradiation Radiation-Protective Agents Gramicidin S General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship 0302 clinical medicine Structure–activity relationship Animals Nitrogen oxides Pharmacology Molecular Structure Radiation-protective agents Dose-Response Relationship Radiation Total body irradiation Mice Inbred C57BL Radiation Injuries Experimental 030104 developmental biology chemistry 030220 oncology & carcinogenesis Biophysics Female Nitrogen Oxides Mitochondrial localization Whole-Body Irradiation Research Article |
| Popis: | Background/aim Mitochondrial-targeted gramicidin S (GS)-nitroxide, JP4-039, has been demonstrated to be a potent radiation mitigator, and safe over a wide dose range. In addition, JP4-039 has organ-specific effectiveness when locally applied. Materials and methods We tested the effect of another GS-nitroxide, XJB-5-131, which has more effective mitochondrial localization, and compared these results to those for radiation mitigation against the hematopoietic syndrome, and two analogs of JP4-039, which have the same mitochondrial localization signal, but different chemical payloads: JRS527.084 contains a second nitroxide per molecule, and TK649.030 contains an ester group attached to the nitroxide. Results The results demonstrate the superiority of JP4-039 as a systemic radiation mitigator. Conclusion Structure-activity relationships and bioassays demonstrate that JP4-039 is an optimized small-molecule radiation mitigator. |
| Databáze: | OpenAIRE |
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